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Current Drug Safety

Editor-in-Chief

ISSN (Print): 1574-8863
ISSN (Online): 2212-3911

Mini-Review Article

Polymeric Micelles as Drug Delivery System: Recent Advances, Approaches, Applications and Patents

Author(s): Anushka Jain*, Kamini Bhardwaj and Mukesh Bansal

Volume 19, Issue 2, 2024

Published on: 23 June, 2023

Page: [163 - 171] Pages: 9

DOI: 10.2174/1574886318666230605120433

Price: $65

Open Access Journals Promotions 2
Abstract

Administering therapeutics through the oral route is a pervasive and widely approved medication administration approach. However, it has been found that many drugs show low systemic absorption when delivered through this route. Such limitations of oral drug delivery can be overcome by polymeric micelles acting as vehicles. As a result, they improve drug absorption by protecting loaded drug substances from the gastrointestinal system's hostile conditions, allowing controlled drug release at a specific site, extending the time spent in the gut through mucoadhesion, and inhibiting the efflux pump from reducing therapeutic agent accumulation. To promote good oral absorption of a weakly water-soluble medicinal drug, the loaded medicine should be protected from the hostile atmosphere of the GI tract. Polymeric micelles can be stacked with a broad assortment of ineffectively dissolvable medications, improving bioavailability. This review discusses the major mechanism, various types, advantages, and limitations for developing the polymeric micelle system and certain micellar drug delivery system applications. The primary goal of this review is to illustrate how polymeric micelles can be used to deliver poorly water-soluble medications.

Keywords: Micelles, polymeric micelles, absorption, copolymer, drug delivery system, water-soluble medications.

Graphical Abstract
[1]
Mourya VK, Inamdar N, Nawale RB, Kulthe SS. Polymeric micelles: General considerations and their applications. Indian J Pharm Educ Res 2011; 45(2): 128-38.
[2]
Adams ML, Lavasanifar A, Kwon GS. Amphiphilic block copolymers for drug delivery. J Pharm Sci 2003; 92(7): 1343-55.
[http://dx.doi.org/10.1002/jps.10397] [PMID: 12820139]
[3]
Moroi Y. Micelles: Theoretical and applied aspects. New York: Springer 2005; pp. 41-50.
[4]
Lee SM, Jang WD. Polyion complex micelle formed from tetraphenylethene containing block copolymer. Biomater Res 2017; 21(1): 17.
[http://dx.doi.org/10.1186/s40824-017-0103-9] [PMID: 29046822]
[5]
Ehrlich P. The relationship existing between chemical constitution, distribution, and pharmacological action. In: The collected papers of Paul Ehrlich. 1956; pp. 596-613.
[6]
Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46(1-3): 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[7]
Fernandez AM. Van derpoorten K, Dasnois L, et al. N-Succinyl-(β-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin: An extracellularly tumor-activated prodrug devoid of intravenous acute toxicity. J Med Chem 2001; 44(22): 3750-3.
[http://dx.doi.org/10.1021/jm0108754] [PMID: 11606140]
[8]
Croy S, Kwon G. Polymeric micelles for drug delivery. Curr Pharm Des 2006; 12(36): 4669-84.
[http://dx.doi.org/10.2174/138161206779026245] [PMID: 17168771]
[9]
Kapare HS, Metkar SR. Micellar drug delivery system: A review. Pharm Res 2020; 2(2): 21-6.
[PMID: 31897616]
[10]
Astafieva I, Zhong XF, Eisenberg A. Critical micellization phenomena in block polyelectrolyte solutions. Macromolecules 1993; 26(26): 7339-52.
[http://dx.doi.org/10.1021/ma00078a034]
[11]
Price C. Micelle formation by block copolymers in organic solvents. Pure Appl Chem 1983; 55(10): 1563-72.
[http://dx.doi.org/10.1351/pac198355101563]
[12]
Ulbrich K, Koňák Č, Tuzar Z, Kopeček J. Solution properties of drug carriers based on poly [N‐(2‐hydroxypropyl) methacrylamide] containing biodegradable bonds. Makromol Chem 1987; 188(6): 1261-72.
[http://dx.doi.org/10.1002/macp.1987.021880604]
[13]
Kralchevsky PA, Danov KD, Denkov ND. Chemical physics of colloid systems and interfaces. In: Handbook of surface and colloid chemistry . 1997; p. 2.
[14]
Heimenz PC. Principles of colloid and surface chemistry. New York M. Dekker 1986.
[15]
Zhang L, Eisenberg A. Thermodynamic vs kinetic aspects in the formation and morphological transitions of crew-cut aggregates produced by self-assembly of polystyrene-b-poly (acrylic acid) block copolymers in dilute solution. Macromolecules 1999; 32(7): 2239-49.
[http://dx.doi.org/10.1021/ma981039f]
[16]
Wanka G, Hoffmann H, Ulbricht W. Phase diagrams and aggregation behavior of poly (oxyethylene)-poly (oxypropylene)-poly (oxyethylene) triblock copolymers in aqueous solutions. Macromolecules 1994; 27(15): 4145-59.
[http://dx.doi.org/10.1021/ma00093a016]
[17]
Allen C, Maysinger D, Eisenberg A. Nano-engineering block copolymer aggregates for drug delivery. Colloids Surf B Biointerfaces 1999; 16(1-4): 3-27.
[http://dx.doi.org/10.1016/S0927-7765(99)00058-2]
[18]
Linse P. Micellization of poly(ethylene oxide)-poly(propylene oxide) block copolymers in aqueous solution. Macromolecules 1993; 26(17): 4437-49.
[http://dx.doi.org/10.1021/ma00069a007]
[19]
Nagarajan R. Solubilization of hydrocarbons and resulting aggregate shape transitions in aqueous solutions of Pluronic® (PEO–PPO–PEO) block copolymers. Colloids Surf B Biointerfaces 1999; 16(1-4): 55-72.
[http://dx.doi.org/10.1016/S0927-7765(99)00061-2]
[20]
Chu B, et al. Nonionic Surfactants: Polyoxyethylene block copolymers. 1996; 67-143.
[21]
Kabanov AV, Alakhov VY. Pluronic® block copolymers in drug delivery: From micellar nanocontainers to biological response modifiers. Criti Rev Therap Drug Carrier Sys 2002; 19(1): 1-72.
[22]
Kwon GS. Polymeric micelles for delivery of poorly water-soluble compounds. Criti Rev Therap Drug Carrier Sys 2003; 20(5): 357-403.
[23]
Bai S, Ma X, Zhang T, et al. Polymeric micelles as delivery systems. Nanoengineered Biomaterials for Advanced Drug Delivery 2020; p. 261.
[24]
Bai S, Zhang X, Ma X, et al. Acid-active supramolecular anticancer nanoparticles based on cyclodextrin polyrotaxanes damaging both mitochondria and nuclei of tumor cells. Biomater Sci 2018; 6(12): 3126-38.
[http://dx.doi.org/10.1039/C8BM01020J] [PMID: 30362476]
[25]
Förster S, Abetz V, Müller AHE. Polyelectrolyte block copolymer micelles. Adv Polym Sci 2004; 166: 173-210.
[http://dx.doi.org/10.1007/b11351]
[26]
Lee AS, Gast AP, Bütün V, Armes SP. Characterizing the structure of pH dependent polyelectrolyte block copolymer micelles. Macromolecules 1999; 32(13): 4302-10.
[http://dx.doi.org/10.1021/ma981865o]
[27]
Guo M, Jiang M. Non-covalently connected micelles (NCCMs): The origins and development of a new concept. Soft Matter 2009; 5(3): 495-500.
[http://dx.doi.org/10.1039/B813556H]
[28]
Orfanou K, Topouza D, Sakellariou G, Pispas S. Graftlike interpolymer complexes from poly(2-vinylpyridine) and end-sulfonic acid polystyrene and polyisoprene: Intermediates to noncovalently bonded block copolymer-like micelles. J Polym Sci A Polym Chem 2003; 41(16): 2454-61.
[http://dx.doi.org/10.1002/pola.10791]
[29]
Duncan R. The dawning era of polymer therapeutics. Nat Rev Drug Discov 2003; 2(5): 347-60.
[http://dx.doi.org/10.1038/nrd1088] [PMID: 12750738]
[30]
Bulmus V, Woodward M, Lin L, Murthy N, Stayton P, Hoffman A. A new pH-responsive and glutathione-reactive, endosomal membrane-disruptive polymeric carrier for intracellular delivery of biomolecular drugs. J Control Release 2003; 93(2): 105-20.
[http://dx.doi.org/10.1016/j.jconrel.2003.06.001] [PMID: 14636717]
[31]
Kabanov AV, Vinogradov SV, Suzdaltseva YG, Alakhov VY. Water-soluble block polycations as carriers for oligonucleotide delivery. Bioconjug Chem 1995; 6(6): 639-43.
[http://dx.doi.org/10.1021/bc00036a001] [PMID: 8608176]
[32]
Harada A, Kataoka K. Formation of polyion complex micelles in an aqueous milieu from a pair of oppositely-charged block copolymers with poly (ethylene glycol) segments. Macromolecules 1995; 28(15): 5294-9.
[http://dx.doi.org/10.1021/ma00119a019]
[33]
Kakizawa Y, Kataoka K. Block copolymer micelles for delivery of gene and related compounds. Adv Drug Deliv Rev 2002; 54(2): 203-22.
[http://dx.doi.org/10.1016/S0169-409X(02)00017-0] [PMID: 11897146]
[34]
Kabanov AV, Kabanov VA. Interpolyelectrolyte and block ionomer complexes for gene delivery: physico-chemical aspects. Adv Drug Deliv Rev 1998; 30(1-3): 49-60.
[http://dx.doi.org/10.1016/S0169-409X(97)00106-3] [PMID: 10837601]
[35]
Kabanov AV, Kabanov VA. DNA complexes with polycations for the delivery of genetic material into cells. Bioconjug Chem 1995; 6(1): 7-20.
[http://dx.doi.org/10.1021/bc00031a002] [PMID: 7711106]
[36]
Gaucher G, Dufresne MH, Sant VP, Kang N, Maysinger D, Leroux JC. Block copolymer micelles: preparation, characterization and application in drug delivery. J Control Release 2005; 109(1-3): 169-88.
[http://dx.doi.org/10.1016/j.jconrel.2005.09.034] [PMID: 16289422]
[37]
des Rieux A, Fievez V, Garinot M, Schneider YJ, Préat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: A mechanistic approach. J Control Release 2006; 116(1): 1-27.
[http://dx.doi.org/10.1016/j.jconrel.2006.08.013] [PMID: 17050027]
[38]
Nishiyama N, Kataoka K. Preparation and characterization of size-controlled polymeric micelle containing cis-dichlorodiammineplatinum(II) in the core. J Control Release 2001; 74(1-3): 83-94.
[http://dx.doi.org/10.1016/S0168-3659(01)00314-5] [PMID: 11489486]
[39]
Vila A, Sánchez A, Tobío M, Calvo P, Alonso MJ. Design of biodegradable particles for protein delivery. J Control Release 2002; 78(1-3): 15-24.
[http://dx.doi.org/10.1016/S0168-3659(01)00486-2] [PMID: 11772445]
[40]
Yamanaka YJ, Leong KW. Engineering strategies to enhance nanoparticle-mediated oral delivery. J Biomater Sci Polym Ed 2008; 19(12): 1549-70.
[http://dx.doi.org/10.1163/156856208786440479] [PMID: 19017470]
[41]
Torchilin VP. Targeted polymeric micelles for delivery of poorly soluble drugs. Cell Mol Life Sci 2004; 61(19-20): 2549-59.
[http://dx.doi.org/10.1007/s00018-004-4153-5] [PMID: 15526161]
[42]
Torchilin V. Polymeric contrast agents for medical imaging. Curr Pharm Biotechnol 2000; 1(2): 183-215.
[http://dx.doi.org/10.2174/1389201003378960] [PMID: 11467336]
[43]
Lukyanov AN, Torchilin VP. Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs. Adv Drug Deliv Rev 2004; 56(9): 1273-89.
[http://dx.doi.org/10.1016/j.addr.2003.12.004] [PMID: 15109769]
[44]
Hong S, Yang Y. Transdermal drug delivery using amphiphilic dendron-coil micelles United States patent application US 14/769,704 2016.
[45]
Ahmed TA, Khalid M, Ahmed OA, Aljaeid BM. In situ gelling composition containing tocopherol-loaded micelles as an intranasal drug delivery system. United States patent US 10,736,843, 2020.
[46]
Zhang F, Yuxiang SH, Huoming LI. Amphiphilic block copolymer, preparation method thereof and nanomicelle drug-loading system. United States patent application US 16/969, 397 2021.
[47]
Sosnik AD. Amphiphilic polymers, process of preparing same and uses thereof. United States patent application US 17/251,802 2021.
[48]
Ahmed OA, Khalid M, Aljaeid BM, Badr-Eldin SM, Ahmed TA. Micellles containing alpha lipoic acid as a transdermal drug delivery system. United States patent US 10,799,455 2020.
[49]
Wang CH, Chen CH, Lin J, Chen JY, Liao WC. Chelating complex micelles drug carrier. United States patent US 9,226,967, 2016.
[50]
Smejkalova D, Huerta-Angeles G, Bobek M, et al. C6-C18 acylated hyaluronic acid derivative, method of preparation thereof, on the basis of nanomicellar composition, method of preparation thereof, and method of preparation of a stabilized nanomicellar composition and use thereof. 2018.
[51]
Gao J, Boothman D, Zhou Y, Bey E. PH-sensitive compositions for delivery of beta lapachone and methods of use. United States patent US 9,631,041 2017.
[52]
Wang CH, Chen CH, Lin J, Chen JY, Liao WC. Drug carrier with chelating complex micelles and the application thereof. United States patent US 8,785,569, 2014.
[53]
Hong S, Bae JW. Amphiphilic dendron-coils, micelles thereof and uses. United States patent US 9,770,413, 2017.
[54]
Lewis AL, Armes SP, Lloyd AW, Jonathan P. Drug carriers comprising amphilphilic block copolymers. United States patent US 9,765,213, 2017.
[55]
Saltzman WM, Zhang J, Zhou J, Jiang Z. Formulations for targeted release of agents to low pH tissue environments or cellular compartments and methods of use thereof. United States patent US 9,895,451 2018.
[56]
Kohn JB, Devore D, Sheihet L, Dubin R. Tri-block copolymers for nanosphere-based drug delivery. United States patent US 8,591,951, 2013.
[57]
Wooley KL, Dorshow RB, Freskos JN, et al. Uniform, functionalized, cross-linked nanostructures for monitoring pH. United States patent application US 15/902,759 2018.
[58]
Giri BP, Gregg K, Singh P, Dagli DJ, Giri A. Hypoxia-targeted polymeric micelles for cancer therapy and imaging. United States patent application US 15/970,162, 2019.
[59]
Tawfik SM, Azizov S, Elmasry MR, Sharipov M, Lee YI. Recent advances in nanomicelles delivery systems. Nanomaterials (Basel) 2020; 11(1): 70.
[http://dx.doi.org/10.3390/nano11010070] [PMID: 33396938]
[60]
Zhu L, Perche F, Wang T, Torchilin VP. Matrix metalloproteinase 2-sensitive multifunctional polymeric micelles for tumor-specific co-delivery of siRNA and hydrophobic drugs. Biomaterials 2014; 35(13): 4213-22.
[http://dx.doi.org/10.1016/j.biomaterials.2014.01.060] [PMID: 24529391]
[61]
Howell M, Mallela J, Wang C, et al. Manganese-loaded lipid-micellar theranostics for simultaneous drug and gene delivery to lungs. J Control Release 2013; 167(2): 210-8.
[http://dx.doi.org/10.1016/j.jconrel.2013.01.029] [PMID: 23395689]
[62]
Majumder NG, Das N, Das SK. Polymeric micelles for anticancer drug delivery. Ther Deliv 2020; 11(10): 613-35.
[http://dx.doi.org/10.4155/tde-2020-0008] [PMID: 32933425]
[63]
Wan X, Beaudoin JJ, Vinod N, et al. Co-delivery of paclitaxel and cisplatin in poly(2-oxazoline) polymeric micelles: Implications for drug loading, release, pharmacokinetics and outcome of ovarian and breast cancer treatments. Biomaterials 2019; 192: 1-14.
[http://dx.doi.org/10.1016/j.biomaterials.2018.10.032] [PMID: 30415101]
[64]
Li Z, Liu M, Ke L, et al. Flexible polymeric nanosized micelles for ophthalmic drug delivery: research progress in the last three years. Nanoscale Adv 2021; 3(18): 5240-54.
[http://dx.doi.org/10.1039/D1NA00596K]
[65]
Su H, Wang F, Ran W, et al. The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers. Proc Natl Acad Sci USA 2020; 117(9): 4518-26.
[http://dx.doi.org/10.1073/pnas.1913655117] [PMID: 32071209]
[66]
Cheng H, Fan X, Wang X, et al. Hierarchically Self-assembled supramolecular host–guest delivery system for drug resistant cancer therapy. Biomacromolecules 2018; 19(6): 1926-38.
[http://dx.doi.org/10.1021/acs.biomac.7b01693] [PMID: 29350902]
[67]
Cheng H, Wu Z, Wu C, et al. Overcoming STC2 mediated drug resistance through drug and gene co -delivery by PHB-PDMAEMA cationic polyester in liver cancer cells. Mater Sci Eng C 2018; 83: 210-7.
[http://dx.doi.org/10.1016/j.msec.2017.08.075] [PMID: 29208281]
[68]
Bravo-Osuna I, Noiray M, Briand E, et al. Interfacial interaction between transmembrane ocular mucins and adhesive polymers and dendrimers analyzed by surface plasmon resonance. Pharm Res 2012; 29(8): 2329-40.
[http://dx.doi.org/10.1007/s11095-012-0761-1] [PMID: 22565639]
[69]
Liu X, Fan X, Jiang L, Loh XJ, Wu YL, Li Z. Biodegradable polyester unimolecular systems as emerging materials for therapeutic applications. J Mater Chem B Mater Biol Med 2018; 6(35): 5488-98.
[http://dx.doi.org/10.1039/C8TB01883A] [PMID: 32254961]
[70]
Zheng Y, Ke L, Lu Y, et al. Enhanced healing and antimicrobial efficacy of chitosan-g-polyacrylamide in a rat model of gingival ulcers. Front Chem 2020; 8: 273.
[http://dx.doi.org/10.3389/fchem.2020.00273] [PMID: 32391317]
[71]
Carrillo-Castillo TD, Castro-Carmona JS, Luna-Velasco A, Zaragoza-Contreras EA. pH-responsive polymer micelles for methotrexate delivery at tumor microenvironments. e-Polymers 2020; 20(1): 624-35.
[72]
Sharipov M, Tawfik SM, Gerelkhuu Z, Huy BT, Lee YI. Phospholipase A2-responsive phosphate micelle-loaded UCNPs for bioimaging of prostate cancer cells. Sci Rep 2017; 7(1): 16073.
[http://dx.doi.org/10.1038/s41598-017-16136-4] [PMID: 29167526]
[73]
Tawfik SM, Huy BT, Sharipov M, Abd-Elaal A, Lee YI. Enhanced fluorescence of CdTe quantum dots capped with a novel nonionic alginate for selective optosensing of ibuprofen. Sens Actuators B Chem 2018; 256: 243-50.
[http://dx.doi.org/10.1016/j.snb.2017.10.092]
[74]
Chen S, Yang K, Tuguntaev RG, et al. Targeting tumor microenvironment with PEG-based amphiphilic nanoparticles to overcome chemoresistance. Nanomedicine 2016; 12(2): 269-86.
[http://dx.doi.org/10.1016/j.nano.2015.10.020] [PMID: 26707818]
[75]
Hari SK, Gauba A, Shrivastava N, Tripathi RM, Jain SK, Pandey AK. Polymeric micelles and cancer therapy: an ingenious multimodal tumor-targeted drug delivery system. Drug Deliv Transl Res 2023; 1(13): 135-63.
[http://dx.doi.org/10.1007/s13346-022-01197-4] [PMID: 35727533]
[76]
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotech 2018 Dec; 16(1): 1-33.
[http://dx.doi.org/10.1186/s12951-018-0392-8]
[77]
Edis Z, Wang J, Waqas MK, Ijaz M, Ijaz M. Nanocarriers-mediated drug delivery systems for anticancer agents: an overview and perspectives. Int J Nanomed 2021; 16: 1313.
[http://dx.doi.org/10.2147/2FIJN.S289443]

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