A Review on Polymeric Invasive and Non-Invasive Nanocarriers Assisted
Transdermal Drug Delivery for Improved Penetration and Bioavailability

Aditya      Sharma; Navneet      Verma; Shashank      Chaturvedi; Neelkant      Prasad; Vaibhav      Rastogi
doi:10.2174/2210303112666220107113135
Abstract

Background: Despite the vast utility of polymeric nanocarriers in drug delivery, their promising role in formulating efficient transdermal drug delivery systems for managing various diseases has not been explored properly.
Introduction: Polymeric nanocarriers have increased the interest of researchers with respect to improving intradermal and transdermal delivery of drugs having ominous penetration and solubility issues. Therefore, a range of invasive and noninvasive approaches have been extensively explored in transdermal delivery systems for the safe and effective transportation of drugs across the skin into the systemic circulation. Accordingly, this review emphasizes the recently used, effectively applicable invasive and noninvasive methodologies for formulating transdermal systems in the form of polymeric films/patches, microneedles, and nanocarriers for better penetration and bioavailability.
Conclusion: Various novel methodologies for transdermal drug delivery systems offer countless benefits over conventional methods, but still, a safe and effective delivery system is the major challenge in terms of reproducible pharmacokinetic and pharmacodynamic results.
Keywords: Bioavailability, methodologies, microneedles, penetration, polymeric nanocarriers, transdermal drug delivery system.
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[1] 
Mitragotri, S.; Burke, P.A.; Langer, R. Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies. Nat. Rev. Drug Discov.,  2014, 13(9), 655-672.
[http://dx.doi.org/10.1038/nrd4363] [PMID:  25103255] 
[2] 
Walter, J.R.; Xu, S. Therapeutic transdermal drug innovation from 2000 to 2014: current status and outlook. Drug Discov. Today,  2015, 20(11), 1293-1299.
[http://dx.doi.org/10.1016/j.drudis.2015.06.007] [PMID:  26116094] 
[3] 
 Global Transdermal Drug Delivery System Market (2020 to 2027)
- COVID-19 Impact and Analysis. Available from: 
          https://www.prnewswire.com/news-releases/global-transdermal-drug-delivery-system-market-2020-to-2027-covid-19-impact-and-analysis-301146587.html (Accessed December 03, 2020)
[4] 
Hadgraft, J.; Lane, M.E. Skin permeation: the years of enlightenment. Int. J. Pharm.,  2005, 305(1-2), 2-12.
[http://dx.doi.org/10.1016/j.ijpharm.2005.07.014] [PMID:  16246513] 
[5] 
Eming, S.A.; Martin, P.; Tomic-Canic, M. Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med.,  2014, 6(265), 265sr6.
[http://dx.doi.org/10.1126/scitranslmed.3009337] [PMID:  25473038] 
[6] 
Finnin, B.C.; Morgan, T.M. Transdermal penetration enhancers: applications, limitations, and potential. J. Pharm. Sci.,  1999, 88(10), 955-958.
[http://dx.doi.org/10.1021/js990154g] [PMID:  10514338] 
[7] 
Barry, B.W. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur. J. Pharm. Sci.,  2001, 14(2), 101-114.
[http://dx.doi.org/10.1016/S0928-0987(01)00167-1] [PMID:  11500256] 
[8] 
Rizwan, M.; Aqil, M.; Talegaonkar, S.; Azeem, A.; Sultana, Y.; Ali, A. Enhanced transdermal drug delivery techniques: an extensive review of patents. Recent Pat. Drug Deliv. Formul.,  2009, 3(2), 105-124.
[http://dx.doi.org/10.2174/187221109788452285] [PMID:  19519571] 
[9] 
Ita, K. Current status of ethosomes and elastic liposomes in dermal and transdermal drug delivery. Curr. Pharm. Des.,  2016, 22(33), 5120-5126.
[http://dx.doi.org/10.2174/1381612822666160511150228] [PMID:  27165164] 
[10] 
Ahmed, T.A. Preparation of transfersomes encapsulating sildenafil aimed for transdermal drug delivery: Plackett-Burman design and characterization. J. Liposome Res.,  2015, 25(1), 1-10.
[http://dx.doi.org/10.3109/08982104.2014.950276] [PMID:  25148294] 
[11] 
Khan, M.A.; Pandit, J.; Sultana, Y.; Sultana, S.; Ali, A.; Aqil, M.; Chauhan, M. Novel carbopol-based transfersomal gel of 5-fluorouracil for skin cancer treatment: in vitro characterization and in vivo study. Drug Deliv.,  2015, 22(6), 795-802.
[http://dx.doi.org/10.3109/10717544.2014.902146] [PMID:  24735246] 
[12] 
Al Shuwaili, A.H.; Rasool, B.K.; Abdulrasool, A.A. Optimization of elastic transfersomes formulations for transdermal delivery of pentoxifylline. Eur. J. Pharm. Biopharm.,  2016, 102, 101-114.
[http://dx.doi.org/10.1016/j.ejpb.2016.02.013] [PMID:  26925505] 
[13] 
Zhai, Y.; Xu, R.; Wang, Y.; Liu, J.; Wang, Z.; Zhai, G. Ethosomes for skin delivery of ropivacaine: Preparation, characterization and ex vivo penetration properties. J. Liposome Res.,  2015, 25(4), 316-324.
[http://dx.doi.org/10.3109/08982104.2014.999686] [PMID:  25625544] 
[14] 
Abdulbaqi, I.M.; Darwis, Y.; Khan, N.A.; Assi, R.A.; Khan, A.A. Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials. Int. J. Nanomedicine,  2016, 11, 2279-2304.
[http://dx.doi.org/10.2147/IJN.S105016] [PMID:  27307730] 
[15] 
Singh, S.; Vardhan, H.; Kotla, N.G.; Maddiboyina, B.; Sharma, D.; Webster, T.J. The role of surfactants in the formulation of elastic liposomal gels containing a synthetic opioid analgesic. Int. J. Nanomedicine,  2016, 11, 1475-1482.
[PMID:  27114707] 
[16] 
Garg, B.J.; Garg, N.K.; Beg, S.; Singh, B.; Katare, O.P. Nanosized ethosomes-based hydrogel formulations of methoxsalen for enhanced topical delivery against vitiligo: formulation optimization, in vitro evaluation and preclinical assessment. J. Drug Target.,  2016, 24(3), 233-246.
[http://dx.doi.org/10.3109/1061186X.2015.1070855] [PMID:  26267289] 
[17] 
Ascenso, A.; Raposo, S.; Batista, C.; Cardoso, P.; Mendes, T.; Praça, F.G.; Bentley, M.V.L.B.; Simões, S. Development, characterization, and skin delivery studies of related ultradeformable vesicles: transfersomes, ethosomes, and transethosomes. Int. J. Nanomedicine,  2015, 10, 5837-5851.
[http://dx.doi.org/10.2147/IJN.S86186] [PMID:  26425085] 
[18] 
Shah, S.M.; Ashtikar, M.; Jain, A.S.; Makhija, D.T.; Nikam, Y.; Gude, R.P.; Steiniger, F.; Jagtap, A.A.; Nagarsenker, M.S.; Fahr, A. LeciPlex, invasomes, and liposomes: A skin penetration study. Int. J. Pharm.,  2015, 490(1-2), 391-403.
[http://dx.doi.org/10.1016/j.ijpharm.2015.05.042] [PMID:  26002568] 
[19] 
Kamran, M.; Ahad, A.; Aqil, M.; Imam, S.S.; Sultana, Y.; Ali, A. Design, formulation and optimization of novel soft nano-carriers for transdermal olmesartan medoxomil delivery: In vitro characterization and in vivo pharmacokinetic assessment. Int. J. Pharm.,  2016, 505(1-2), 147-158.
[http://dx.doi.org/10.1016/j.ijpharm.2016.03.030] [PMID:  27005906] 
[20] 
Kim, Y.C.; Park, J.H.; Prausnitz, M.R. Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev.,  2012, 64(14), 1547-1568.
[http://dx.doi.org/10.1016/j.addr.2012.04.005] [PMID:  22575858] 
[21] 
 Mishra, A.N. Transdermal drug delivery. Controlled and Novel
drug delivery; Jain, N.K., Ed.; CBS Publishers and Distributers:
New Delhi, 2002, 4, pp. 100-129.
[22] 
Prausnitz, M.R.; Langer, R. Transdermal drug delivery. Nat. Biotechnol.,  2008, 26(11), 1261-1268.
[http://dx.doi.org/10.1038/nbt.1504] [PMID:  18997767] 
[23] 
Escobar-Chavez, J.J.; Rodriguez-Cruz, I.M.; Dominguez-Delgado, C.L.; Diaz-Torres, R.; Revilla-Vazquez, A.L. Nanocarrier systems for transdermal drug delivery. Recent Advances in Novel Drug Carrier Systems; Sezer, A.D., Ed.; IntechOpen Limited: London, UK, 2012, Vol. 1, pp. 201-240.
[24] 
Carrer, V.; Alonso, C.; Pont, M.; Zanuy, M.; Córdoba, M.; Espinosa, S.; Barba, C.; Oliver, M.A.; Martí, M.; Coderch, L. Effect of propylene glycol on the skin penetration of drugs. Arch. Dermatol. Res.,  2020, 312(5), 337-352.
[http://dx.doi.org/10.1007/s00403-019-02017-5] [PMID:  31786711] 
[25] 
Szunerits, S.; Boukherroub, R. Heat: A highly efficient skin enhancer for transdermal drug delivery. Front. Bioeng. Biotechnol.,  2018, 6, 15.
[http://dx.doi.org/10.3389/fbioe.2018.00015] [PMID:  29497609] 
[26] 
Ng, K.W.; Lau, W.M. Skin Deep: The basics of human skin structure and drug penetration. Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement: Drug Manipulation Strategies and Vehicle Effects; Dragicevic, N; Maibach, H.I., Ed.; Springer: Berlin, Heidelberg, 2015, Vol. 1, pp. 3-11.
[27] 
 Flynn, G.L. Cutaneous and transdermal delivery: Processes and
systems of delivery. Modern Pharmaceutics; Banker, G.S.; Rhodes,
C.T., Eds.; Marcel Dekker, New York: NY, 1996, 121, pp. 239-
299.
[28] 
McCarley, K.D.; Bunge, A.L. Pharmacokinetic models of dermal absorption. J. Pharm. Sci.,  2001, 90(11), 1699-1719.
[http://dx.doi.org/10.1002/jps.1120] [PMID:  11745728] 
[29] 
Fang, C.L.; Aljuffali, I.A.; Li, Y.C.; Fang, J.Y. Delivery and targeting of nanoparticles into hair follicles. Ther. Deliv.,  2014, 5(9), 991-1006.
[http://dx.doi.org/10.4155/tde.14.61] [PMID:  25375342] 
[30] 
McAllister, D.V.; Wang, P.M.; Davis, S.P.; Park, J.H.; Canatella, P.J.; Allen, M.G.; Prausnitz, M.R. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc. Natl. Acad. Sci. USA,  2003, 100(24), 13755-13760.
[http://dx.doi.org/10.1073/pnas.2331316100] [PMID:  14623977] 
[31] 
 Dhaval, R.; Kalaria, D.R.; Dubey, S.; Kalia, Y.N. Clinical applications
of transdermal iontophoresis. Transdermal and Topical Drug Delivery: Principles and Practice; Benson, H.A.E.; Watkinson,
A.C., Eds.; John Wiley & Sons: Hoboken, New Jersey, 2012, 1, pp.
67-84.
[32] 
Kaushik, S.; Hord, A.H.; Denson, D.D.; McAllister, D.V.; Smitra, S.; Allen, M.G.; Prausnitz, M.R. Lack of pain associated with microfabricated microneedles. Anesth. Analg.,  2001, 92(2), 502-504.
[http://dx.doi.org/10.1213/00000539-200102000-00041] [PMID:  11159258] 
[33] 
Kim, Y.C.; Prausnitz, M.R. Enabling skin vaccination using new delivery technologies. Drug Deliv. Transl. Res.,  2011, 1(1), 7-12.
[http://dx.doi.org/10.1007/s13346-010-0005-z] [PMID:  21799951] 
[34] 
Raphael, A.P.; Prow, T.W.; Crichton, M.L.; Chen, X.; Fernando, G.J.P.; Kendall, M.A.F. Targeted, needle-free vaccinations in skin using multilayered, densely-packed dissolving microprojection arrays. Small,  2010, 6(16), 1785-1793.
[http://dx.doi.org/10.1002/smll.201000326] [PMID:  20665628] 
[35] 
Sullivan, S.P.; Koutsonanos, D.G.; Del Pilar Martin, M.; Lee, J.W.; Zarnitsyn, V.; Choi, S.O.; Murthy, N.; Compans, R.W.; Skountzou, I.; Prausnitz, M.R. Dissolving polymer microneedle patches for influenza vaccination. Nat. Med.,  2010, 16(8), 915-920.
[http://dx.doi.org/10.1038/nm.2182] [PMID:  20639891] 
[36] 
Kretsos, K.; Kasting, G.B. Dermal capillary clearance: physiology and modeling. Skin Pharmacol. Physiol.,  2005, 18(2), 55-74.
[http://dx.doi.org/10.1159/000083706] [PMID:  15767767] 
[37] 
Lambert, P.H.; Laurent, P.E. Intradermal vaccine delivery: will new delivery systems transform vaccine administration? Vaccine,  2008, 26(26), 3197-3208.
[http://dx.doi.org/10.1016/j.vaccine.2008.03.095] [PMID:  18486285] 
[38] 
Mikszta, J.A.; Laurent, P.E. Cutaneous delivery of prophylactic and therapeutic vaccines: Historical perspective and future outlook. Expert Rev. Vaccines,  2008, 7(9), 1329-1339.
[http://dx.doi.org/10.1586/14760584.7.9.1329] [PMID:  18980537] 
[39] 
Simon, L.; Goyal, A. Dynamics and control of percutaneous drug absorption in the presence of epidermal turnover. J. Pharm. Sci.,  2009, 98(1), 187-204.
[http://dx.doi.org/10.1002/jps.21408] [PMID:  18481307] 
[40] 
Al-Zahrani, S.; Zaric, M.; McCrudden, C.; Scott, C.; Kissenpfennig, A.; Donnelly, R.F. Microneedle-mediated vaccine delivery: Harnessing cutaneous immunobiology to improve efficacy. Expert Opin. Drug Deliv.,  2012, 9(5), 541-550.
[http://dx.doi.org/10.1517/17425247.2012.676038] [PMID:  22475249] 
[41] 
Segura, E.; Villadangos, J.A. Antigen presentation by dendritic cells in vivo. Curr. Opin. Immunol.,  2009, 21(1), 105-110.
[http://dx.doi.org/10.1016/j.coi.2009.03.011] [PMID:  19342210] 
[42] 
Zaba, L.C.; Krueger, J.G.; Lowes, M.A. Resident and “inflammatory” dendritic cells in human skin. J. Invest. Dermatol.,  2009, 129(2), 302-308.
[http://dx.doi.org/10.1038/jid.2008.225] [PMID:  18685620] 
[43] 
Gupta, J.; Gill, H.S.; Andrews, S.N.; Prausnitz, M.R. Kinetics of skin resealing after insertion of microneedles in human subjects. J. Control. Release,  2011, 154(2), 148-155.
[http://dx.doi.org/10.1016/j.jconrel.2011.05.021] [PMID:  21640148] 
[44] 
Alarcon, J.B.; Hartley, A.W.; Harvey, N.G.; Mikszta, J.A. Preclinical evaluation of microneedle technology for intradermal delivery of influenza vaccines. Clin. Vaccine Immunol.,  2007, 14(4), 375-381.
[http://dx.doi.org/10.1128/CVI.00387-06] [PMID:  17329444] 
[45] 
Mitragotri, S. Immunization without needles. Nat. Rev. Immunol.,  2005, 5(12), 905-916.
[http://dx.doi.org/10.1038/nri1728] [PMID:  16239901] 
[46] 
Lee, J.W.; Park, J.H.; Prausnitz, M.R. Dissolving microneedles for transdermal drug delivery. Biomaterials,  2008, 29(13), 2113-2124.
[http://dx.doi.org/10.1016/j.biomaterials.2007.12.048] [PMID:  18261792] 
[47] 
Sullivan, S.P.; Murthy, N.; Prausnitz, M.R. Minimally invasive protein delivery with rapidly dissolving polymer microneedles. Adv. Mater.,  2008, 20(5), 933-938.
[http://dx.doi.org/10.1002/adma.200701205] [PMID:  23239904] 
[48] 
Park, J.H.; Allen, M.G.; Prausnitz, M.R. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J. Control. Release,  2005, 104(1), 51-66.
[http://dx.doi.org/10.1016/j.jconrel.2005.02.002] [PMID:  15866334] 
[49] 
Moga, K.A.; Bickford, L.R.; Geil, R.D.; Dunn, S.S.; Pandya, A.A.; Wang, Y.; Fain, J.H.; Archuleta, C.F.; O’Neill, A.T.; Desimone, J.M. Rapidly-dissolvable microneedle patches via a highly scalable and reproducible soft lithography approach. Adv. Mater.,  2013, 25(36), 5060-5066.
[http://dx.doi.org/10.1002/adma.201300526] [PMID:  23893866] 
[50] 
Lee, J.W.; Han, M.R.; Park, J.H. Polymer microneedles for transdermal drug delivery. J. Drug Target.,  2013, 21(3), 211-223.
[http://dx.doi.org/10.3109/1061186X.2012.741136] [PMID:  23167609] 
[51] 
Lee, K.; Lee, C.Y.; Jung, H. Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. Biomaterials,  2011, 32(11), 3134-3140.
[http://dx.doi.org/10.1016/j.biomaterials.2011.01.014] [PMID:  21292317] 
[52] 
Gupta, J.; Felner, E.I.; Prausnitz, M.R. Minimally invasive insulin delivery in subjects with type 1 diabetes using hollow microneedles. Diabetes Technol. Ther.,  2009, 11(6), 329-337.
[http://dx.doi.org/10.1089/dia.2008.0103] [PMID:  19459760] 
[53] 
Gill, H.S.; Prausnitz, M.R. Coating formulations for microneedles. Pharm. Res.,  2007, 24(7), 1369-1380.
[http://dx.doi.org/10.1007/s11095-007-9286-4] [PMID:  17385011] 
[54] 
Kim, Y.C.; Quan, F.S.; Compans, R.W.; Kang, S.M.; Prausnitz, M.R. Formulation and coating of microneedles with inactivated influenza virus to improve vaccine stability and immunogenicity. J. Control. Release,  2010, 142(2), 187-195.
[http://dx.doi.org/10.1016/j.jconrel.2009.10.013] [PMID:  19840825] 
[55] 
Langer, R.; Folkman, J. Polymers for the sustained release of proteins and other macromolecules. Nature,  1976, 263(5580), 797-800.
[http://dx.doi.org/10.1038/263797a0] [PMID:  995197] 
[56] 
van der Maaden, K.; Jiskoot, W.; Bouwstra, J. Microneedle technologies for (trans)dermal drug and vaccine delivery. J. Control. Release,  2012, 161(2), 645-655.
[http://dx.doi.org/10.1016/j.jconrel.2012.01.042] [PMID:  22342643] 
[57] 
Herwadkar, A.; Banga, A.K. Peptide and protein transdermal drug delivery. Drug Discov. Today. Technol.,  2012, 9(2), e71-e174.
[http://dx.doi.org/10.1016/j.ddtec.2011.11.007] [PMID:  24064275] 
[58] 
Wu, F.; Yang, S.; Yuan, W.; Jin, T. Challenges and strategies in developing microneedle patches for transdermal delivery of protein and peptide therapeutics. Curr. Pharm. Biotechnol.,  2012, 13(7), 1292-1298.
[http://dx.doi.org/10.2174/138920112800624319] [PMID:  22201589] 
[59] 
Sun, W.; Hu, Q.; Ji, W.; Wright, G.; Gu, Z. Leveraging physiology for precision drug delivery. Physiol. Rev.,  2017, 97, 189-225.
[http://dx.doi.org/10.1152/physrev.00015.2016] 
[60] 
Yu, J.; Zhang, Y.; Kahkoska, A.R.; Gu, Z. Bioresponsive transcutaneous patches. Curr. Opin. Biotechnol.,  2017, 48, 28-32.
[http://dx.doi.org/10.1016/j.copbio.2017.03.001] [PMID:  28292673] 
[61] 
Lu, Y.; Aimetti, A.A.; Langer, R.; Gu, Z. Bioresponsive materials. Nat. Rev. Mater.,  2017, 2, 16075.
[http://dx.doi.org/10.1038/natrevmats.2016.75] 
[62] 
Mahapatro, A.; Singh, D.K. Biodegradable nanoparticles are excellent vehicle for site directed in-vivo delivery of drugs and vaccines. J. Nanobiotechnology,  2011, 9, 55.
[http://dx.doi.org/10.1186/1477-3155-9-55] [PMID:  22123084] 
[63] 
Taghizadeh, B.; Taranejoo, S.; Monemian, S.A.; Salehi Moghaddam, Z.; Daliri, K.; Derakhshankhah, H.; Derakhshani, Z. Classification of stimuli-responsive polymers as anticancer drug delivery systems. Drug Deliv.,  2015, 22(2), 145-155.
[http://dx.doi.org/10.3109/10717544.2014.887157] [PMID:  24547737] 
[64] 
Mura, S.; Nicolas, J.; Couvreur, P. Stimuli-responsive nanocarriers for drug delivery. Nat. Mater.,  2013, 12(11), 991-1003.
[http://dx.doi.org/10.1038/nmat3776] [PMID:  24150417] 
[65] 
de Las Heras Alarcon, C.; Pennadam, S.; Alexander, C. Stimuli responsive polymers for biomedical applications. Chem. Soc. Rev.,  2005, 34(3), 276-285.
[http://dx.doi.org/10.1039/B406727D] [PMID:  15726163] 
[66] 
Peer, D.; Karp, J.M.; Hong, S.; Farokhzad, O.C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol.,  2007, 2(12), 751-760.
[http://dx.doi.org/10.1038/nnano.2007.387] [PMID:  18654426] 
[67] 
Park, J.H.; Choi, S.O.; Kamath, R.; Yoon, Y.K.; Allen, M.G.; Prausnitz, M.R. Polymer particle-based micromolding to fabricate novel microstructures. Biomed. Microdevices,  2007, 9(2), 223-234.
[http://dx.doi.org/10.1007/s10544-006-9024-4] [PMID:  17195110] 
[68] 
Stuart, M.A.C.; Huck, W.T.S.; Genzer, J.; Müller, M.; Ober, C.; Stamm, M.; Sukhorukov, G.B.; Szleifer, I.; Tsukruk, V.V.; Urban, M.; Winnik, F.; Zauscher, S.; Luzinov, I.; Minko, S. Emerging applications of stimuli-responsive polymer materials. Nat. Mater.,  2010, 9(2), 101-113.
[http://dx.doi.org/10.1038/nmat2614] [PMID:  20094081] 
[69] 
Gholami, S.; Mohebi, M.M.; Hajizadeh-Saffar, E.; Ghanian, M.H.; Zarkesh, I.; Baharvand, H. Fabrication of microporous inorganic microneedles by centrifugal casting method for transdermal extraction and delivery. Int. J. Pharm.,  2019, 558, 299-310.
[http://dx.doi.org/10.1016/j.ijpharm.2018.12.089] [PMID:  30654056] 
[70] 
 Chen, W.; Tian, R.; Xu, C.; Yung, B.C.; Wang, G.; Liu, Y.; Ni, Q.;
Zhang, F.; Zhou, Z.; Wang, J.; Niu, G.; Ma, Y.; Fu, L.; Chen, X.
Microneedle-array patches loaded with dual mineralized protein/
peptide particles for type 2 diabetes therapy. Nat. comm., 8,
1777.2017,
[71] 
Ye, Y.; Yu, J.; Wang, C.; Nguyen, N.Y.; Walker, G.M.; Buse, J.B.; Gu, Z. Microneedles integrated with pancreatic cells and synthetic glucose-signal amplifiers for smart insulin delivery. Adv. Mater.,  2016, 28(16), 3115-3121.
[http://dx.doi.org/10.1002/adma.201506025] [PMID:  26928976] 
[72] 
Yu, J.; Qian, C.; Zhang, Y.; Cui, Z.; Zhu, Y.; Shen, Q.; Ligler, F.S.; Buse, J.B.; Gu, Z. Hypoxia and H2O2 dual-sensitive vesicles for enhanced glucose-responsive insulin delivery. Nano Lett.,  2017, 17(2), 733-739.
[http://dx.doi.org/10.1021/acs.nanolett.6b03848] [PMID:  28079384] 
[73] 
Hong, X.; Wei, L.; Wu, F.; Wu, Z.; Chen, L.; Liu, Z.; Yuan, W. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des. Devel. Ther.,  2013, 7, 945-952.
[PMID:  24039404] 
[74] 
An, M.; Liu, H. Dissolving microneedle arrays for transdermal delivery of amphiphilic vaccines. Small,  2017, 13(26), 1700164.
[http://dx.doi.org/10.1002/smll.201700164] [PMID:  28544329] 
[75] 
Tucak, A.; Sirbubalo, M.; Hindija, L.; Rahić, O.; Hadžiabdić, J.;
Muhamedagić, K.; Čekić, A.; Vranić, E. Microneedles: Characteristics, materials, production methods and commercial development. Micromachines (Basel),  2020, 11(11), 1-30.
[http://dx.doi.org/10.3390/mi11110961] [PMID:  33121041] 
[76] 
Lee, J.W.; Choi, S.O.; Felner, E.I.; Prausnitz, M.R. Dissolving microneedle patch for transdermal delivery of human growth hormone. Small,  2011, 7(4), 531-539.
[http://dx.doi.org/10.1002/smll.201001091] [PMID:  21360810] 
[77] 
Miyano, T.; Tobinaga, Y.; Kanno, T.; Matsuzaki, Y.; Takeda, H.; Wakui, M.; Hanada, K. Sugar micro needles as transdermic drug delivery system. Biomed. Microdevices,  2005, 7(3), 185-188.
[http://dx.doi.org/10.1007/s10544-005-3024-7] [PMID:  16133805] 
[78] 
Chen, M.C.; Ling, M.H.; Lai, K.Y.; Pramudityo, E. Chitosan microneedle patches for sustained transdermal delivery of macromolecules. Biomacromolecules,  2012, 13(12), 4022-4031.
[http://dx.doi.org/10.1021/bm301293d] [PMID:  23116140] 
[79] 
Chu, L.Y.; Choi, S.O.; Prausnitz, M.R. Fabrication of dissolving polymer microneedles for controlled drug encapsulation and delivery: Bubble and pedestal microneedle designs. J. Pharm. Sci.,  2010, 99(10), 4228-4238.
[http://dx.doi.org/10.1002/jps.22140] [PMID:  20737630] 
[80] 
Ramöller, I.K.; Tekko, I.A.; McCarthy, H.O.; Donnelly, R.F. Rapidly dissolving bilayer microneedle arrays - A minimally invasive transdermal drug delivery system for vitamin B12. Int. J. Pharm.,  2019, 566, 299-306.
[http://dx.doi.org/10.1016/j.ijpharm.2019.05.066] [PMID:  31150773] 
[81] 
Yao, W.; Tao, C.; Zou, J.; Zheng, H.; Zhu, J.; Zhu, Z.; Zhu, J.; Liu, L.; Li, F.; Song, X. Flexible two-layer dissolving and safing microneedle transdermal of neurotoxin: A biocomfortable attempt to treat Rheumatoid Arthritis. Int. J. Pharm.,  2019, 563, 91-100.
[http://dx.doi.org/10.1016/j.ijpharm.2019.03.033] [PMID:  30890451] 
[82] 
Yao, G.; Quan, G.; Lin, S.; Peng, T.; Wang, Q.; Ran, H.; Chen, H.; Zhang, Q.; Wang, L.; Pan, X.; Wu, C. Novel dissolving microneedles for enhanced transdermal delivery of levonorgestrel: In vitro and in vivo characterization. Int. J. Pharm.,  2017, 534(1-2), 378-386.
[http://dx.doi.org/10.1016/j.ijpharm.2017.10.035] [PMID:  29051119] 
[83] 
Prausnitz, M.R.; Mitragotri, S.; Langer, R. Current status and future potential of transdermal drug delivery. Nat. Rev. Drug Discov.,  2004, 3(2), 115-124.
[http://dx.doi.org/10.1038/nrd1304] [PMID:  15040576] 
[84] 
Park, J.H.; Allen, M.G.; Prausnitz, M.R. Polymer microneedles for controlled-release drug delivery. Pharm. Res.,  2006, 23(5), 1008-1019.
[http://dx.doi.org/10.1007/s11095-006-0028-9] [PMID:  16715391] 
[85] 
Kim, M.; Jung, B.; Park, J.H. Hydrogel swelling as a trigger to release biodegradable polymer microneedles in skin. Biomaterials,  2012, 33(2), 668-678.
[http://dx.doi.org/10.1016/j.biomaterials.2011.09.074] [PMID:  22000788] 
[86] 
Ye, Y.; Wang, C.; Zhang, X.; Hu, Q.; Zhang, Y.; Liu, Q.; Wen, D.; Milligan, J.; Bellotti, A.; Huang, L.; Dotti, G.; Gu, Z. A melanin-mediated cancer immunotherapy patch. Sci. Immunol.,  2017, 2(17), eaan5692.
[http://dx.doi.org/10.1126/sciimmunol.aan5692] [PMID:  29127106] 
[87] 
Zaric, M.; Lyubomska, O.; Touzelet, O.; Poux, C.; Al-Zahrani, S.; Fay, F.; Wallace, L.; Terhorst, D.; Malissen, B.; Henri, S.; Power, U.F.; Scott, C.J.; Donnelly, R.F.; Kissenpfennig, A. Skin dendritic cell targeting via microneedle arrays laden with antigen-encapsulated poly-D,L-lactide-co-glycolide nanoparticles induces efficient antitumor and antiviral immune responses. ACS Nano,  2013, 7(3), 2042-2055.
[http://dx.doi.org/10.1021/nn304235j] [PMID:  23373658] 
[88] 
Brazzle, J.D.; Papautsky, I.; Frazier, A.B. Hollow metallic micromachined needle arrays. Biomed. Microdevices,  2000, 2, 197-205.
[http://dx.doi.org/10.1023/A:1009980412628] 
[89] 
Davis, S.P.; Landis, B.J.; Adams, Z.H.; Allen, M.G.; Prausnitz, M.R. Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. J. Biomech.,  2004, 37(8), 1155-1163.
[http://dx.doi.org/10.1016/j.jbiomech.2003.12.010] [PMID:  15212920] 
[90] 
Paik, S.J.; Byun, S.; Lim, J.M.; Park, Y.; Lee, A.; Chung, S.; Chang, J.; Chun, K.; Cho, D. In-plane single-crystal-silicon microneedles for minimally invasive microfluid systems. Sens. Actuators A Phys.,  2004, 114(2-3), 276-284.
[http://dx.doi.org/10.1016/j.sna.2003.12.029] 
[91] 
Harvey, A.J.; Kaestner, S.A.; Sutter, D.E.; Harvey, N.G.; Mikszta, J.A.; Pettis, R.J. Microneedle-based intradermal delivery enables rapid lymphatic uptake and distribution of protein drugs. Pharm. Res.,  2011, 28(1), 107-116.
[http://dx.doi.org/10.1007/s11095-010-0123-9] [PMID:  20354765] 
[92] 
Davis, S.P.; Martanto, W.; Allen, M.G.; Prausnitz, M.R. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans. Biomed. Eng.,  2005, 52(5), 909-915.
[http://dx.doi.org/10.1109/TBME.2005.845240] [PMID:  15887540] 
[93] 
Martanto, W.; Moore, J.S.; Couse, T.; Prausnitz, M.R. Mechanism of fluid infusion during microneedle insertion and retraction. J. Control. Release,  2006, 112(3), 357-361.
[http://dx.doi.org/10.1016/j.jconrel.2006.02.017] [PMID:  16626836] 
[94] 
Wang, P.M.; Cornwell, M.; Hill, J.; Prausnitz, M.R. Precise microinjection into skin using hollow microneedles. J. Invest. Dermatol.,  2006, 126(5), 1080-1087.
[http://dx.doi.org/10.1038/sj.jid.5700150] [PMID:  16484988] 
[95] 
Martanto, W.; Moore, J.S.; Kashlan, O.; Kamath, R.; Wang, P.M.; O’Neal, J.M.; Prausnitz, M.R. Microinfusion using hollow microneedles. Pharm. Res.,  2006, 23(1), 104-113.
[http://dx.doi.org/10.1007/s11095-005-8498-8] [PMID:  16308670] 
[96] 
Bodhale, D.W.; Nisar, A.; Afzulpurkar, N. Structural and microfluidic analysis of hollow sideopen polymeric microneedles for transdermal drug delivery applications. Microfluid. Nanofluidics,  2010, 8, 373-392.
[http://dx.doi.org/10.1007/s10404-009-0467-9] 
[97] 
Chua, B.; Desai, S.P.; Tierney, M.J.; Tamada, J.A.; Jina, A.N. Effect of microneedles shape on skin penetration and minimally invasive continuous glucose monitoring in vivo. Sens. Actuators A Phys.,  2013, 203, 373-381.
[http://dx.doi.org/10.1016/j.sna.2013.09.026] 
[98] 
van der Maaden, K.; Heuts, J.; Camps, M.; Pontier, M.; Terwisscha van Scheltinga, A.; Jiskoot, W.; Ossendorp, F.; Bouwstra, J. Hollow microneedle-mediated micro-injections of a liposomal HPV E743-63 synthetic long peptide vaccine for efficient induction of cytotoxic and T-helper responses. J. Control. Release,  2018, 269, 347-354.
[http://dx.doi.org/10.1016/j.jconrel.2017.11.035] [PMID:  29174441] 
[99] 
Verbaan, F.J.; Bal, S.M.; van den Berg, D.J.; Groenink, W.H.; Verpoorten, H.; Lüttge, R.; Bouwstra, J.A. Assembled microneedle arrays enhance the transport of compounds varying over a large range of molecular weight across human dermatomed skin. J. Control. Release,  2007, 117(2), 238-245.
[http://dx.doi.org/10.1016/j.jconrel.2006.11.009] [PMID:  17196697] 
[100] 
Mikszta, J.A.; Dekker, J.P., III; Harvey, N.G.; Dean, C.H.; Brittingham, J.M.; Huang, J.; Sullivan, V.J.; Dyas, B.; Roy, C.J.; Ulrich, R.G. Microneedle-based intradermal delivery of the anthrax recombinant protective antigen vaccine. Infect. Immun.,  2006, 74(12), 6806-6810.
[http://dx.doi.org/10.1128/IAI.01210-06] [PMID:  17030580] 
[101] 
Laurent, P.E.; Bourhy, H.; Fantino, M.; Alchas, P.; Mikszta, J.A. Safety and efficacy of novel dermal and epidermal microneedle delivery systems for rabies vaccination in healthy adults. Vaccine,  2010, 28(36), 5850-5856.
[http://dx.doi.org/10.1016/j.vaccine.2010.06.062] [PMID:  20600481] 
[102] 
Ogundele, M.; Okafor, H.K. Transdermal drug delivery: Microneedles, their fabrication and current trends in delivery methods. J. Pharm. Res. Int.,  2017, 18(5), 1-14.
[http://dx.doi.org/10.9734/JPRI/2017/36164] 
[103] 
Henry, S.; McAllister, D.V.; Allen, M.G.; Prausnitz, M.R. Microfabricated microneedles: A novel approach to transdermal drug delivery. J. Pharm. Sci.,  1998, 87(8), 922-925.
[http://dx.doi.org/10.1021/js980042+] [PMID:  9687334] 
[104] 
Eltayib, E.; Brady, A.J.; Caffarel-Salvador, E.; Gonzalez-Vazquez, P.; Zaid Alkilani, A.; McCarthy, H.O.; McElnay, J.C.; Donnelly, R.F. Hydrogel-forming microneedle arrays: Potential for use in minimally-invasive lithium monitoring. Eur. J. Pharm. Biopharm.,  2016, 102, 123-131.
[http://dx.doi.org/10.1016/j.ejpb.2016.03.009] [PMID:  26969262] 
[105] 
Dimatteo, R.; Darling, N.J.; Segura, T. In situ forming injectable hydrogels for drug delivery and wound repair. Adv. Drug Deliv. Rev.,  2018, 127, 167-184.
[http://dx.doi.org/10.1016/j.addr.2018.03.007] [PMID:  29567395] 
[106] 
Kiang, T.K.L.; Ranamukhaarachchi, S.A.; Ensom, M.H.H. Revolutionizing therapeutic drug monitoring with the use of interstitial fluid and microneedles technology. Pharmaceutics,  2017, 9(4), 43.
[http://dx.doi.org/10.3390/pharmaceutics9040043] [PMID:  29019915] 
[107] 
Donnelly, R.F.; McCrudden, M.T.; Zaid Alkilani, A.; Larrañeta, E.; McAlister, E.; Courtenay, A.J.; Kearney, M.C.; Singh, T.R.R.; McCarthy, H.O.; Kett, V.L.; Caffarel-Salvador, E.; Al-Zahrani, S.; Woolfson, A.D. Hydrogel-forming microneedles prepared from “super swelling” polymers combined with lyophilised wafers for transdermal drug delivery. PLoS One,  2014, 9(10), e111547.
[http://dx.doi.org/10.1371/journal.pone.0111547] [PMID:  25360806] 
[108] 
Larrañeta, E.; McCrudden, M.T.; Courtenay, A.J.; Donnelly, R.F. Microneedles: A new frontier in nanomedicine delivery. Pharm. Res.,  2016, 33(5), 1055-1073.
[http://dx.doi.org/10.1007/s11095-016-1885-5] [PMID:  26908048] 
[109] 
Yao, W.; Li, D.; Zhao, Y.; Zhan, Z.; Jin, G.; Liang, H.; Yang, R., 3D Printed multi-functional hydrogel microneedles based on high-precision digital light processing. Micromachines (Basel),  2019, 11(1), 17.
[http://dx.doi.org/10.3390/mi11010017] [PMID:  31877987] 
[110] 
Chen, X.; Fernando, G.J.; Crichton, M.L.; Flaim, C.; Yukiko, S.R.; Fairmaid, E.J.; Corbett, H.J.; Primiero, C.A.; Ansaldo, A.B.; Frazer, I.H.; Brown, L.E.; Kendall, M.A.F. Improving the reach of vaccines to low-resource regions, with a needle-free vaccine delivery device and long-term thermostabilization. J. Control. Release,  2011, 152(3), 349-355.
[http://dx.doi.org/10.1016/j.jconrel.2011.02.026] [PMID:  21371510] 
[111] 
Gill, H.S.; Prausnitz, M.R. Coated microneedles for transdermal delivery. J. Control. Release,  2007, 117(2), 227-237.
[http://dx.doi.org/10.1016/j.jconrel.2006.10.017] [PMID:  17169459] 
[112] 
Donnelly, R.F.; Raj Singh, T.R.; Woolfson, A.D. Microneedle-based drug delivery systems: microfabrication, drug delivery, and safety. Drug Deliv.,  2010, 17(4), 187-207.
[http://dx.doi.org/10.3109/10717541003667798] [PMID:  20297904] 
[113] 
Zeng, Q.; Gammon, J.M.; Tostanoski, L.H.; Chiu, Y.C.; Jewell, C.M. In vivo expansion of melanoma-specific T cells using microneedle arrays coated with immune-polyelectrolyte multilayers. ACS Biomater. Sci. Eng.,  2017, 3(2), 195-205.
[http://dx.doi.org/10.1021/acsbiomaterials.6b00414] [PMID:  28286864] 
[114] 
Zhu, Q.; Zarnitsyn, V.G.; Ye, L.; Wen, Z.; Gao, Y.; Pan, L.; Skountzou, I.; Gill, H.S.; Prausnitz, M.R.; Yang, C.; Compans, R.W. Immunization by vaccine-coated microneedle arrays protects against lethal influenza virus challenge. Proc. Natl. Acad. Sci. USA,  2009, 106(19), 7968-7973.
[http://dx.doi.org/10.1073/pnas.0812652106] [PMID:  19416832] 
[115] 
Narayanan, S.P.; Raghavan, S. Fabrication and characterization of gold-coated solid silicon microneedles with improved biocompatibility. Int. J. Adv. Manuf. Technol.,  2019, 104, 3327-3333.
[http://dx.doi.org/10.1007/s00170-018-2596-3] 
[116] 
Martanto, W.; Davis, S.P.; Holiday, N.R.; Wang, J.; Gill, H.S.; Prausnitz, M.R. Transdermal delivery of insulin using microneedles in vivo. Pharm. Res.,  2004, 21(6), 947-952.
[http://dx.doi.org/10.1023/B:PHAM.0000029282.44140.2e] [PMID:  15212158] 
[117] 
Yeung, C.; Chen, S.; King, B.; Lin, H.; King, K.; Akhtar, F.; Diaz, G.; Wang, B.; Zhu, J.; Sun, W.; Khademhosseini, A.; Emaminejad, S. A 3D-printed microfluidic-enabled hollow microneedle architecture for transdermal drug delivery. Biomicrofluidics,  2019, 13(6), 064125.
[http://dx.doi.org/10.1063/1.5127778] [PMID:  31832123] 
[118] 
Rzhevskiy, A.S.; Singh, T.R.R.; Donnelly, R.F.; Anissimov, Y.G. Microneedles as the technique of drug delivery enhancement in diverse organs and tissues. J. Control. Release,  2018, 270, 184-202.
[http://dx.doi.org/10.1016/j.jconrel.2017.11.048] [PMID:  29203415] 
[119] 
Naguib, Y.W.; Kumar, A.; Cui, Z. The effect of microneedles on the skin permeability and antitumor activity of topical 5-fluorouracil. Acta Pharm. Sin. B,  2014, 4(1), 94-99.
[http://dx.doi.org/10.1016/j.apsb.2013.12.013] [PMID:  25313350] 
[120] 
Cormier, M.; Johnson, B.; Ameri, M.; Nyam, K.; Libiran, L.; Zhang, D.D.; Daddona, P. Transdermal delivery of desmopressin using a coated microneedle array patch system. J. Control. Release,  2004, 97(3), 503-511.
[http://dx.doi.org/10.1016/S0168-3659(04)00171-3] [PMID:  15212882] 
[121] 
Donnelly, R.F.; Morrow, D.I.; Singh, T.R.R.; Migalska, K.; McCarron, P.A.; O’Mahony, C.; Woolfson, A.D. Processing difficulties and instability of carbohydrate microneedle arrays. Drug Dev. Ind. Pharm.,  2009, 35(10), 1242-1254.
[http://dx.doi.org/10.1080/03639040902882280] [PMID:  19555249] 
[122] 
Gujjar, M.; Banga, A.K. Iontophoretic and microneedle mediated transdermal delivery of glycopyrrolate. Pharmaceutics,  2014, 6(4), 663-671.
[http://dx.doi.org/10.3390/pharmaceutics6040663] [PMID:  25533309] 
[123] 
Liu, S.; Jin, M.N.; Quan, Y.S.; Kamiyama, F.; Katsumi, H.; Sakane, T.; Yamamoto, A. The development and characteristics of novel microneedle arrays fabricated from hyaluronic acid, and their application in the transdermal delivery of insulin. J. Control. Release,  2012, 161(3), 933-941.
[http://dx.doi.org/10.1016/j.jconrel.2012.05.030] [PMID:  22634072] 
[124] 
Nguyen, H.X.; Bozorg, B.D.; Kim, Y.; Wieber, A.; Birk, G.; Lubda, D.; Banga, A.K. Poly (vinyl alcohol) microneedles: Fabrication, characterization, and application for transdermal drug delivery of doxorubicin. Eur. J. Pharm. Biopharm.,  2018, 129, 88-103.
[http://dx.doi.org/10.1016/j.ejpb.2018.05.017] [PMID:  29800617] 
[125] 
Langer, R. New methods of drug delivery. Science,  1990, 249(4976), 1527-1533.
[http://dx.doi.org/10.1126/science.2218494] [PMID:  2218494] 
[126] 
Mikszta, J.A.; Alarcon, J.B.; Brittingham, J.M.; Sutter, D.E.; Pettis, R.J.; Harvey, N.G. Improved genetic immunization via micromechanical disruption of skin-barrier function and targeted epidermal delivery. Nat. Med.,  2002, 8(4), 415-419.
[http://dx.doi.org/10.1038/nm0402-415] [PMID:  11927950] 
[127] 
Qadri, G.R.; Ahad, A.; Aqil, M.; Imam, S.S.; Ali, A. Invasomes of isradipine for enhanced transdermal delivery against hypertension: formulation, characterization, and in vivo pharmacodynamic study. Artif. Cells Nanomed. Biotechnol.,  2017, 45(1), 139-145.
[http://dx.doi.org/10.3109/21691401.2016.1138486] [PMID:  26829018] 
[128] 
Soliman, K.A.; Ibrahim, H.K.; Ghorab, M.M. Effects of different combinations of nanocrystallization technologies on avanafil nanoparticles: In vitro, in vivo and stability evaluation. Int. J. Pharm.,  2017, 517(1-2), 148-156.
[http://dx.doi.org/10.1016/j.ijpharm.2016.12.012] [PMID:  27939570] 
[129] 
El-Say, K.M.; Ahmed, T.A.; Badr-Eldin, S.M.; Fahmy, U.; Aldawsari, H.; Ahmed, O.A.A. Enhanced permeation parameters of optimized nanostructured simvastatin transdermal films: ex vivo and in vivo evaluation. Pharm. Dev. Technol.,  2015, 20(8), 919-926.
[http://dx.doi.org/10.3109/10837450.2014.938859] [PMID:  25019166] 
[130] 
Badr-Eldin, S.M.; Ahmed, O.A.A. Optimized nano-transfersomal films for enhanced sildenafil citrate transdermal delivery: Ex vivo and in vivo evaluation. Drug Des. Devel. Ther.,  2016, 10, 1323-1333.
[http://dx.doi.org/10.2147/DDDT.S103122] [PMID:  27103786] 
[131] 
Yang, Z.; Teng, Y.; Wang, H.; Hou, H. Enhancement of skin permeation of bufalin by limonene via reservoir type transdermal patch: formulation design and biopharmaceutical evaluation. Int. J. Pharm.,  2013, 447(1-2), 231-240.
[http://dx.doi.org/10.1016/j.ijpharm.2013.02.048] [PMID:  23467076] 
[132] 
Dubey, V.; Mishra, D.; Dutta, T.; Nahar, M.; Saraf, D.K.; Jain, N.K. Dermal and transdermal delivery of an anti-psoriatic agent via ethanolic liposomes. J. Control. Release,  2007, 123(2), 148-154.
[http://dx.doi.org/10.1016/j.jconrel.2007.08.005] [PMID:  17884226] 
[133] 
Ahmed, O.A.A.; Badr-Eldin, S.M. Development of an optimized avanafil-loaded invasomal transdermal film: Ex vivo skin permeation and in vivo evaluation. Int. J. Pharm.,  2019, 570, 118657.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118657] [PMID:  31491483] 
[134] 
Nair, A.B.; Gupta, S.; Al-Dhubiab, B.E.; Jacob, S.; Shinu, P.; Shah, J.; Morsy, M.A. SreeHarsha, N.; Attimarad, M.; Venugopala, K.N.; Akrawi, S.H. Effective therapeutic delivery and bioavailability enhancement of pioglitazone using drug in adhesive transdermal patch. Pharmaceutics,  2019, 11(7), 359.
[http://dx.doi.org/10.3390/pharmaceutics11070359] [PMID:  31340601] 
[135] 
Rastogi, V.; Yadav, P.; Husain, A.; Verma, A. Effect of hydrophilic and hydrophobic polymers on permeation of S-amlodipine besylate through intercalated polymeric transdermal matrix: 3(2) designing, optimization and characterization. Drug Dev. Ind. Pharm.,  2019, 45(4), 669-682.
[http://dx.doi.org/10.1080/03639045.2019.1569035] [PMID:  30633579] 
[136] 
Rastogi, V.; Kumar, A.; Porwal, M.; Mishra, A.K.; Rastogi, V.; Verma, N.; Verma, A. Enhancement of skin permeation of glibenclamide from ethyl cellulose- polyvinyl pyrollidone based transdermal patches using olive oil and mustard oil as penetration enhancer: In vitro, ex-vivo and in vivo evaluation. Drug Deliv. Lett.,  2015, 5(2), 109-121.
[http://dx.doi.org/10.2174/2210303105666150728205154] 
[137] 
Altamimi, M.A.; Kazi, M.; Hadi Albgomi, M.; Ahad, A.; Raish, M. Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure. Drug Dev. Ind. Pharm.,  2019, 45(7), 1073-1078.
[http://dx.doi.org/10.1080/03639045.2019.1593440] [PMID:  30987466] 
[138] 
Abd El-Alim, S.H.; Kassem, A.A.; Basha, M.; Salama, A. Comparative study of liposomes, ethosomes and transfersomes as carriers for enhancing the transdermal delivery of diflunisal: In vitro and in vivo evaluation. Int. J. Pharm.,  2019, 563, 293-303.
[http://dx.doi.org/10.1016/j.ijpharm.2019.04.001] [PMID:  30951860] 
[139] 
Yamazaki, N.; Yamakawa, S.; Sugimoto, T.; Yoshizaki, Y.; Teranishi, R.; Hayashi, T.; Kotaka, A.; Shinde, C.; Kumei, T.; Sumida, Y.; Shimizu, T.; Ohashi, Y.; Yuba, E.; Harada, A.; Kono, K. Carboxylated phytosterol derivative-introduced liposomes for skin environment-responsive transdermal drug delivery system. J. Liposome Res.,  2018, 28(4), 275-284.
[http://dx.doi.org/10.1080/08982104.2017.1369995] [PMID:  28826275] 
[140] 
Abdel-Messih, H.A.; Ishak, R.A.H.; Geneidi, A.S.; Mansour, S. Tailoring novel soft nano-vesicles ‘Flexosomes’ for enhanced transdermal drug delivery: Optimization, characterization and comprehensive ex vivo-in vivo evaluation. Int. J. Pharm.,  2019, 560, 101-115.
[http://dx.doi.org/10.1016/j.ijpharm.2019.01.072] [PMID:  30753931] 
[141] 
Mahmood, S.; Mandal, U.K.; Chatterjee, B. Transdermal delivery of raloxifene HCl via ethosomal system: Formulation, advanced characterizations and pharmacokinetic evaluation. Int. J. Pharm.,  2018, 542(1-2), 36-46.
[http://dx.doi.org/10.1016/j.ijpharm.2018.02.044] [PMID:  29501737] 
[142] 
Ahmed, T.A.; El-Say, K.M.; Aljaeid, B.M.; Fahmy, U.A.; Abd-Allah, F.I. Transdermal glimepiride delivery system based on optimized ethosomal nano-vesicles: Preparation, characterization, in vitro, ex vivo and clinical evaluation. Int. J. Pharm.,  2016, 500(1-2), 245-254.
[http://dx.doi.org/10.1016/j.ijpharm.2016.01.017] [PMID:  26775063] 
[143] 
Hirakawa, Y.; Ueda, H.; Miyano, T.; Kamiya, N.; Goto, M. New insight into transdermal drug delivery with supersaturated formulation based on co-amorphous system. Int. J. Pharm.,  2019, 569, 118582.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118582] [PMID:  31381987] 
[144] 
Ngo, H.V.; Tran, P.H.L.; Lee, B.J.; Tran, T.T.D. Development of film-forming gel containing nanoparticles for transdermal drug delivery. Nanotechnology,  2019, 30(41), 415102.
[http://dx.doi.org/10.1088/1361-6528/ab2e29] [PMID:  31261146] 
[145] 
Gu, Y.; Tang, X.; Yang, M.; Yang, D.; Liu, J. Transdermal drug delivery of triptolide-loaded nanostructured lipid carriers: Preparation, pharmacokinetic, and evaluation for rheumatoid arthritis. Int. J. Pharm.,  2019, 554, 235-244.
[http://dx.doi.org/10.1016/j.ijpharm.2018.11.024] [PMID:  30423415] 
[146] 
Mendes, A.C.; Gorzelanny, C.; Halter, N.; Schneider, S.W.; Chronakis, I.S. Hybrid electrospun chitosan-phospholipids nanofibers for transdermal drug delivery. Int. J. Pharm.,  2016, 510(1), 48-56.
[http://dx.doi.org/10.1016/j.ijpharm.2016.06.016] [PMID:  27286632] 
[147] 
Carmona-Moran, C.A.; Zavgorodnya, O.; Penman, A.D.; Kharlampieva, E.; Bridges, S.L., Jr; Hergenrother, R.W.; Singh, J.A.; Wick, T.M. Development of gellan gum containing formulations for transdermal drug delivery: Component evaluation and controlled drug release using temperature responsive nanogels. Int. J. Pharm.,  2016, 509(1-2), 465-476.
[http://dx.doi.org/10.1016/j.ijpharm.2016.05.062] [PMID:  27260133] 
[148] 
Elgindy, N.A.; Mehanna, M.M.; Mohyeldin, S.M. Self-assembled nano-architecture liquid crystalline particles as a promising carrier for progesterone transdermal delivery. Int. J. Pharm.,  2016, 501(1-2), 167-179.
[http://dx.doi.org/10.1016/j.ijpharm.2016.01.049] [PMID:  26828671] 
[149] 
Mathur, V.; Satrawala, Y.; Rajput, M.S. Physical and chemical penetration enhancers in transdermal drug delivery system. Asian J. Pharm.,  2010, 4(3), 173-183.
[http://dx.doi.org/10.4103/0973-8398.72115] 
[150] 
Shaker, D.S.; Ishak, R.A.H.; Ghoneim, A.; Elhuoni, M.A. Nanoemulsion: A review on mechanisms for the transdermal delivery of hydrophobic and hydrophilic drugs. Sci. Pharm.,  2019, 87(3), 17.
[http://dx.doi.org/10.3390/scipharm87030017] 
[151] 
Kommuru, T.R.; Gurley, B.; Khan, M.A.; Reddy, I.K. Self-emulsifying drug delivery systems (SEDDS) of coenzyme Q10: formulation development and bioavailability assessment. Int. J. Pharm.,  2001, 212(2), 233-246.
[http://dx.doi.org/10.1016/S0378-5173(00)00614-1] [PMID:  11165081] 
[152] 
Yadav, P.; Rastogi, V.; Verma, A. Application of Box–Behnken design and desirability function in the development and optimization of self-nanoemulsifying drug delivery system for enhanced dissolution of ezetimibe. Future J. Pharm. Sci.,  2020, 6, 7.
[http://dx.doi.org/10.1186/s43094-020-00023-3] 
[153] 
Natsheh, H.; Touitou, E. Phospholipid vesicles for dermal/transdermal and nasal administration of active molecules: The effect of surfactants and alcohols on the fluidity of their lipid bilayers and penetration enhancement properties. Molecules,  2020, 25(13), 2959.
[http://dx.doi.org/10.3390/molecules25132959] [PMID:  32605117] 
[154] 
Mura, P.; Capasso, G.; Maestrelli, F.; Furlanetto, S. Optimization of formulation variables of benzocaine liposomes using experimental design. J. Liposome Res.,  2008, 18(2), 113-125.
[http://dx.doi.org/10.1080/08982100802118540] [PMID:  18569447] 
[155] 
Trotta, M.; Peira, E.; Carlotti, M.E.; Gallarate, M. Deformable liposomes for dermal administration of methotrexate. Int. J. Pharm.,  2004, 270(1-2), 119-125.
[http://dx.doi.org/10.1016/j.ijpharm.2003.10.006] [PMID:  14726128] 
[156] 
Thong, H.Y.; Zhai, H.; Maibach, H.I. Percutaneous penetration enhancers: an overview. Skin Pharmacol. Physiol.,  2007, 20(6), 272-282.
[http://dx.doi.org/10.1159/000107575] [PMID:  17717423] 
[157] 
El Zaafarany, G.M.; Awad, G.A.; Holayel, S.M.; Mortada, N.D. Role of edge activators and surface charge in developing ultradeformable vesicles with enhanced skin delivery. Int. J. Pharm.,  2010, 397(1-2), 164-172.
[http://dx.doi.org/10.1016/j.ijpharm.2010.06.034] [PMID:  20599487] 
[158] 
Cevc, G.; Blume, G. Lipid vesicles penetrate into intact skin owing to the transdermal osmotic gradients and hydration force. Biochim. Biophys. Acta,  1992, 1104(1), 226-232.
[http://dx.doi.org/10.1016/0005-2736(92)90154-E] [PMID:  1550849] 
[159] 
El Maghraby, G.M.; Williams, A.C.; Barry, B.W. Skin delivery of 5-fluorouracil from ultradeformable and standard liposomes in-vitro. J. Pharm. Pharmacol.,  2001, 53(8), 1069-1077.
[http://dx.doi.org/10.1211/0022357011776450] [PMID:  11518016] 
[160] 
Sinico, C.; Fadda, A.M. Vesicular carriers for dermal drug delivery. Expert Opin. Drug Deliv.,  2009, 6(8), 813-825.
[http://dx.doi.org/10.1517/17425240903071029] [PMID:  19569979] 
[161] 
Touitou, E.; Dayan, N.; Bergelson, L.; Godin, B.; Eliaz, M. Ethosomes - novel vesicular carriers for enhanced delivery: characterization and skin penetration properties. J. Control. Release,  2000, 65(3), 403-418.
[http://dx.doi.org/10.1016/S0168-3659(99)00222-9] [PMID:  10699298] 
[162] 
Chen, Z.X.; Li, B.; Liu, T.; Wang, X.; Zhu, Y.; Wang, L.; Wang, X.H.; Niu, X.; Xiao, Y.; Sun, Q. Evaluation of paeonol-loaded transethosomes as transdermal delivery carriers. Eur. J. Pharm. Sci.,  2017, 99, 240-245.
[http://dx.doi.org/10.1016/j.ejps.2016.12.026] [PMID:  28039091] 
[163] 
Shahriar, S.M.S.; Mondal, J.; Hasan, M.N.; Revuri, V.; Lee, D.Y.; Lee, Y.K. Electrospinning nanofibers for therapeutics delivery. Nanomaterials (Basel),  2019, 9(4), E532.
[http://dx.doi.org/10.3390/nano9040532] [PMID:  30987129] 
[164] 
Rastogi, V.; Yadav, P.; Bhattacharya, S.S.; Mishra, A.K.; Verma, N.; Verma, A.; Pandit, J.K. Carbon nanotubes: An emerging drug carrier for targeting cancer cells. J. Drug Deliv.,  2014, 2014, 670815.
[http://dx.doi.org/10.1155/2014/670815] [PMID:  24872894] 
[165] 
Ariamoghaddam, A.R.; Ebrahimi-Hosseinzadeh, B.; Hatamian-Zarmi, A.; Sahraeian, R. in vivo anti-obesity efficacy of curcumin loaded nanofibers transdermal patches in high-fat diet induced obese rats. Mater. Sci. Eng. C,  2018, 92, 161-171.
[http://dx.doi.org/10.1016/j.msec.2018.06.030] [PMID:  30184739] 
[166] 
Sahu, P.; Kashaw, S.K.; Kushwah, V.; Sau, S.; Jain, S.; Iyer, A.K. pH responsive biodegradable nanogels for sustained release of bleomycin. Bioorg. Med. Chem.,  2017, 25(17), 4595-4613.
[http://dx.doi.org/10.1016/j.bmc.2017.06.038] [PMID:  28734664] 
[167] 
Ita, K. Transdermal iontophoretic drug delivery: Advances and challenges. J. Drug Target.,  2016, 24(5), 386-391.
[http://dx.doi.org/10.3109/1061186X.2015.1090442] [PMID:  26406291] 
[168] 
Lee, H.; Song, C.; Baik, S.; Kim, D.; Hyeon, T.; Kim, D.H. Device-assisted transdermal drug delivery. Adv. Drug Deliv. Rev.,  2018, 127, 35-45.
[http://dx.doi.org/10.1016/j.addr.2017.08.009] [PMID:  28867296] 
[169] 
Kalia, Y.N.; Naik, A.; Garrison, J.; Guy, R.H. Iontophoretic drug delivery. Adv. Drug Deliv. Rev.,  2004, 56(5), 619-658.
[http://dx.doi.org/10.1016/j.addr.2003.10.026] [PMID:  15019750] 
[170] 
Meidan, V.M.; Al-Khalili, M.; Michniak, B.B. Enhanced iontophoretic delivery of buspirone hydrochloride across human skin using chemical enhancers. Int. J. Pharm.,  2003, 264(1-2), 73-83.
[http://dx.doi.org/10.1016/S0378-5173(03)00390-9] [PMID:  12972337] 
[171] 
Chesnoy, S.; Durand, D.; Doucet, J.; Couarraze, G. Structural parameters involved in the permeation of propranolol HCl by iontophoresis and enhancers. J. Control. Release,  1999, 58(2), 163-175.
[http://dx.doi.org/10.1016/S0168-3659(98)00155-2] [PMID:  10053189] 
[172] 
Raiman, J.; Koljonen, M.; Huikko, K.; Kostiainen, R.; Hirvonen, J. Delivery and stability of LHRH and Nafarelin in human skin: the effect of constant/pulsed iontophoresis. Eur. J. Pharm. Sci.,  2004, 21(2-3), 371-377.
[http://dx.doi.org/10.1016/j.ejps.2003.11.003] [PMID:  14757511] 
[173] 
Burnette, R.R.; Marrero, D. Comparison between the iontophoretic and passive transport of thyrotropin releasing hormone across excised nude mouse skin. J. Pharm. Sci.,  1986, 75(8), 738-743.
[http://dx.doi.org/10.1002/jps.2600750803] [PMID:  3095533] 
[174] 
van der Geest, R.; van Laar, T.; Gubbens-Stibbe, J.M.; Boddé, H.E.; Danhof, M. Iontophoretic delivery of apomorphine. II: An in vivo study in patients with Parkinson’s disease. Pharm. Res.,  1997, 14(12), 1804-1810.
[http://dx.doi.org/10.1023/A:1012152401715] [PMID:  9453072] 
[175] 
Grice, J.E.; Prow, T.W.; Kendall, M.A.F.; Roberts, M.S In: Electrical and physical methods of skin penetration enhancement in: Transdermal and topical drug delivery: principles and practice; Benson, H.A.E.; Watkinson, A.C., Eds.; John Wiley & Sons: Hoboken, New Jersey, 2012; 1, p. 55.
[176] 
Hui, S.W. Overview of drug delivery and alternative methods to electroporation. Methods Mol. Biol.,  2008, 423, 91-107.
[http://dx.doi.org/10.1007/978-1-59745-194-9_6] [PMID:  18370192] 
[177] 
Wong, T.W.; Zhao, Y.L.; Sen, A.; Hui, S.W. Pilot study of topical delivery of methotrexate by electroporation. Br. J. Dermatol.,  2005, 152(3), 524-530.
[http://dx.doi.org/10.1111/j.1365-2133.2005.06455.x] [PMID:  15787822] 
[178] 
Denet, A.R.; Préat, V. Transdermal delivery of timolol by electroporation through human skin. J. Control. Release,  2003, 88(2), 253-262.
[http://dx.doi.org/10.1016/S0168-3659(03)00010-5] [PMID:  12628332] 
[179] 
Vanbever, R.; LeBoulengé, E.; Préat, V. Transdermal delivery of fentanyl by electroporation. I. Influence of electrical factors. Pharm. Res.,  1996, 13(4), 559-565.
[http://dx.doi.org/10.1023/A:1016093920875] [PMID:  8710746] 
[180] 
Hu, Q.; Liang, W.; Bao, J.; Ping, Q. Enhanced transdermal delivery of tetracaine by electroporation. Int. J. Pharm.,  2000, 202(1-2), 121-124.
[http://dx.doi.org/10.1016/S0378-5173(00)00432-4] [PMID:  10915934] 
[181] 
Zhang, L.; Lerner, S.; Rustrum, W.V.; Hofmann, G.A. Electroporation-mediated topical delivery of vitamin C for cosmetic applications. Bioelectrochem. Bioenerg.,  1999, 48(2), 453-461.
[http://dx.doi.org/10.1016/S0302-4598(99)00026-4] [PMID:  10379568] 
[182] 
Fang, J.Y.; Hung, C.F.; Hwang, T.L.; Wong, W.W. Transdermal delivery of tea catechins by electrically assisted methods. Skin Pharmacol. Physiol.,  2006, 19(1), 28-37.
[http://dx.doi.org/10.1159/000089141] [PMID:  16247247] 
[183] 
Sersa, G.; Miklavcic, D.; Cemazar, M.; Rudolf, Z.; Pucihar, G.; Snoj, M. Electrochemotherapy in treatment of tumours. Eur. J. Surg. Oncol.,  2008, 34(2), 232-240.
[http://dx.doi.org/10.1016/j.ejso.2007.05.016] [PMID:  17614247] 
[184] 
Tokumoto, S.; Higo, N.; Sugibayashi, K. Effect of electroporation and pH on the iontophoretic transdermal delivery of human insulin. Int. J. Pharm.,  2006, 326(1-2), 13-19.
[http://dx.doi.org/10.1016/j.ijpharm.2006.07.002] [PMID:  16920293] 
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DOI https://dx.doi.org/10.2174/2210303112666220107113135	Print ISSN 2210-3031
Publisher Name Bentham Science Publisher	Online ISSN 2210-304X
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