Robotic Pills as Innovative Personalized Medicine Tools: A Mini Review

Komal      Rane; Garima      Kukreja; Siddhi      Deshmukh; Urmisha      Kakad; Pranali      Jadhav; Vinita      Patole

doi:10.2174/0126673878265457231205114925

Abstract

The most common route for drug administration is the oral route due to the various advantages offered by this route, such as ease of administration, controlled and sustained drug delivery, convenience, and non-invasiveness. In spite of this, oral drug absorption faces challenges due to various issues related to its stability, permeability and solubility in the GI tract. Biologic drugs generally face problems when administered by oral route as they are readily degradable and thus required to be injected. To overcome these issues in oral absorption, different approaches like novel drug delivery systems and newer pharmaceutical technologies have been adopted. With a combined knowledge of drug delivery and pharmaceutical technology, robotic pills can be designed and used successfully to enhance the adhesion and permeation of drugs through the mucus membrane of the GI tract to achieve drug delivery at the target site. The potential application of robotic pills in diagnosis and drug dispensing is also discussed. The review highlights recent developments in robotic pill drug-device technology and discusses its potential applications to solve the problems and challenges in oral drug delivery.

Keywords: Robotic pill, oral delivery, biologics, GI tract, non-invasiveness, rheumatoid arthritis.

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[1]
Streubel A, Siepmann J, Bodmeier R. Gastroretentive drug delivery systems. Expert Opin Drug Deliv  2006; 3(2): 217-33.
 [http://dx.doi.org/10.1517/17425247.3.2.217] [PMID:  16506949]

[2]
Macierzanka A, Mackie AR, Krupa L. Permeability of the small intestinal mucus for physiologically relevant studies: Impact of mucus location and ex vivo treatment. Sci Rep  2019; 9(1): 17516.
 [http://dx.doi.org/10.1038/s41598-019-53933-5] [PMID:  31772308]

[3]
Tyagi P, Pechenov S, Subramony JA. Oral peptide delivery:
Translational challenges due to physiological effects. 2018; 287: 167-76.

[4]
Hua S. Advances in oral drug delivery for regional targeting in the gastrointestinal tract - influence of physiological, pathophysiological and pharmaceutical factors. Front Pharmacol  2020; 11: 524.
 [http://dx.doi.org/10.3389/fphar.2020.00524] [PMID:  32425781]

[5]
Philip AK, Philip B. Colon targeted drug delivery systems: A review on primary and novel approaches 2010; 2: 70-8.
 [http://dx.doi.org/10.5001/omj.2010.24]

[6]
Anselmo AC, Gokarn Y, Mitragotri S. Non-invasive delivery strategies for biologics 2018; 18: 19-40.

[7]
Mauritz MA, Morrisby RS, Hutton RS, Legge CH, Kaminski CF. Imaging pharmaceutical tablets with optical coherence tomography. 2010; 99(1): 385-91.
 [http://dx.doi.org/10.1002/jps.21844]

[8]
Quan G, Niu B, Singh V, Zhou Y, Wu CY, Pan X, et al. Super
saturable solid self-micro emulsifying drug delivery system: Precipitation
inhibition and bioavailability enhancement 2017; 12: 8801-11.

[9]
Kumar A, Nautiyal U, Kaur C. Targeted drug delivery system:
Current and novel approach. www.ijpmr.org

[10]
Macadam A. The effect of gastro-intestinal mucus on drug absorption 1993; 11: 201-20.
 [http://dx.doi.org/10.1016/0169-409X(93)90010-2]

[11]
Xu Y, Shrestha N, Préat V, Beloqui A. Overcoming the intestinal barrier: A look into targeting approaches for improved oral drug delivery systems 2020; 322: 486-508.
 [http://dx.doi.org/10.1016/j.jconrel.2020.04.006]

[12]
Caffarel-Salvador E, Abramson A, Langer R, Traverso G. Oral delivery of biologics using drug-device combinations 2017; 36: 8-13.
 [http://dx.doi.org/10.1016/j.coph.2017.07.003]

[13]
Zema L, Loreti G, Melocchi A, Maroni A, Palugan L, Gazzaniga A. Gastroresistant capsular device prepared by injection molding 2013; 440(2): 264-72.
 [http://dx.doi.org/10.1016/j.ijpharm.2012.05.071]

[14]
Zahn JD, Talbot NH, Liepmann D, Pisano AP. Microfabricated polysilicon microneedles for minimally invasive biomedical devices 2000; 2

[15]
Mandsberg NK, Christfort JF, Kamguyan K, Boisen A, Srivastava SK. Orally ingestible medical devices for gut engineering 2020; 165: 142-54.
 [http://dx.doi.org/10.1016/j.addr.2020.05.004]

[16]
Valdivia PC, Robertson AR, De Boer NKH, Marlicz W, Koulaouzidis A. An overview of robotic capsules for drug delivery to the gastrointestinal tract 2021; 10

[17]
Dhalla AK, Al-Shamsie Z, Beraki S, Dasari A, Fung LC, Fusaro L, et al. A robotic pill for oral delivery of biotherapeutics: Safety,
tolerability, and performance in healthy subjects 2022; 12(1): 294-305.
 [http://dx.doi.org/10.1007/s13346-021-00938-1]

[18]
Abramson A, Frederiksen MR, Vegge A, Jensen B, Poulsen M, Mouridsen B, et al. Oral delivery of systemic monoclonal antibodies, peptides and small molecules using gastric auto-injectors 2022; 40(1): 103-9.
 [http://dx.doi.org/10.1038/s41587-021-01024-0]

[19]
Cummins G. Smart pills for gastrointestinal diagnostics and therapy 2021; 177
 [http://dx.doi.org/10.1016/j.addr.2021.113931]

[20]
Tang Q, Jin G, Wang G, Liu T, Liu X, Wang B, et al. Current sampling methods for gut microbiota: A call for more precise devices 2020; 10
 [http://dx.doi.org/10.3389/fcimb.2020.00151]

[21]
Jovel J, Dieleman LA, Kao D, Mason AL, Wine E. The human gut microbiome in health and disease. In: Metagenomics: Perspectives,
Methods, and Applications.   2017; pp. 197-213.

[22]
Hou K, Wu ZX, Chen XY, et al. Microbiota in health and diseases. Signal Transduct Target Ther  2022; 7(1): 135.
 [http://dx.doi.org/10.1038/s41392-022-00974-4] [PMID:  35461318]

[23]
Soto F, Purcell E, Ozen MO, Sinawang PD, Wang J, Akin D, et al. Robotic pill for biomarker and fluid sampling in the gastrointestinal tract 2022; (6): 220-30.

[24]
Engineering IEEE. Engineering in medicine and biology society,
institute of electrical and electronics engineers. 40th Annual international
conference of the IEEE engineering in medicine and biology
society: Learning from the past, looking to the future. Hawaii
Convention Center, Honolulu, Hawaii.   2018; pp. 17-21.

[25]
Le Z, Yu J, Quek YJ, Bai B, Li X, Shou Y, et al. Design principles of microneedles for drug delivery and sampling applications 2022.

[26]
Finocchiaro M, Giosuè C, Drago G, Cibella F, Menciassi A, Sprovieri M, et al. Design of a magnetic actuation system for a microbiota-collection ingestible capsule. IEEE International Conference on Robotics and Automation.  6905-11.
 [http://dx.doi.org/10.1109/ICRA48506.2021.9561142]

[27]
Moglia A, Menciassi A, Schurr MO, Dario P. Wireless capsule
endoscopy: From diagnostic devices to multipurpose robotic systems 2007; 9(2): 235-43.

[28]
Jaison A, Simon A, Christin A, John N, Varghese N. v MY. Robotic pill dispenser. IOSR J Pharm Biol Sci  2014; 9(4): 51-4.
 [http://dx.doi.org/10.9790/3008-09455154]

[29]
Farid SF. Conceptual framework of the impact of health technology on healthcare system  2019; 10
 [http://dx.doi.org/10.3389/fphar.2019.00933]

[30]
Tsai PH, Chen TY, Yu CR, Shih CS, Liu JWS. Smart medication dispenser: Design, architecture and implementation. IEEE Syst J  2011; 5(1): 99-110.
 [http://dx.doi.org/10.1109/JSYST.2010.2070970]

[31]
Aldeer M, Javanmard M, Martin R. A review of medication adherence monitoring technologies. Applied System Innovation  2018; 1(2): 14.
 [http://dx.doi.org/10.3390/asi1020014]

[32]
Mason M, Cho Y, Rayo J, Gong Y, Harris M, Jiang Y. Technologies for medication adherence monitoring and technology assessment criteria: Narrative review. JMIR Mhealth Uhealth  2022; 10(3): e35157.
 [http://dx.doi.org/10.2196/35157] [PMID:  35266873]

[33]
Karagiannis D, Mitsis K, Nikita KS. Development of a low-power IoMT portable pillbox for medication adherence improvement and remote treatment adjustment. Sensors  2022; 22(15): 5818.
 [http://dx.doi.org/10.3390/s22155818] [PMID:  35957374]

[34]
Soto F, Purcell E, Ozen MO, et al. Robotic pill for biomarker and fluid sampling in the gastrointestinal tract. Adv Intell Syst  2022; 4(6): 2200030.
 [http://dx.doi.org/10.1002/aisy.202200030]

[35]
Cummins G. Smart pills for gastrointestinal diagnostics and therapy. Adv Drug Deliv Rev  2021; 177: 113931.
 [http://dx.doi.org/10.1016/j.addr.2021.113931] [PMID:  34416311]

[36]
Rehan M, Al-Bahadly I, Thomas DG, Avci E. Development of a robotic capsule for in vivo sampling of gut microbiota. IEEE Robot Autom Lett  2022; 7(4): 9517-24.
 [http://dx.doi.org/10.1109/LRA.2022.3191177]

[37]
Denecke K, Baudoin CR. A review of artificial intelligence and robotics in transformed health ecosystems. Front Med  2022; 9: 795957.
 [http://dx.doi.org/10.3389/fmed.2022.795957] [PMID:  35872767]

[38]
ElGibreen H, Al Ali G, AlMegren R, AlEid R, AlQahtani S. Telepresence robot system for people with speech or mobility disabilities. Sensors  2022; 22(22): 8746.
 [http://dx.doi.org/10.3390/s22228746] [PMID:  36433341]

[39]
Calatrava-Nicolás FM, Gutiérrez-Maestro E, Bautista-Salinas D, et al. Robotic-based well-being monitoring and coaching system for the elderly in their daily activities. Sensors  2021; 21(20): 6865.
 [http://dx.doi.org/10.3390/s21206865] [PMID:  34696078]

[40]
Gutkin E, Shalomov A, Hussain SA, et al. Pillcam ESO ® is more accurate than clinical scoring systems in risk stratifying emergency room patients with acute upper gastrointestinal bleeding. Therap Adv Gastroenterol  2013; 6(3): 193-8.
 [http://dx.doi.org/10.1177/1756283X13481020] [PMID:  23634183]

[41]
Omori T, Hara T, Sakasai S, et al. Does the PillCam SB3 capsule endoscopy system improve image reading efficiency irrespective of experience? A pilot study. Endosc Int Open  2018; 6(6): E669-75.
 [http://dx.doi.org/10.1055/a-0599-5852] [PMID:  29868632]

[42]
Carvalho PB, Rosa B, Castro FD, Moreira MJ, Cotter J. PillCam COLON 2 © in Crohn’s disease: A new concept of pan-enteric mucosal healing assessment. World J Gastroenterol  2015; 21(23): 7233-41.
 [http://dx.doi.org/10.3748/wjg.v21.i23.7233] [PMID:  26109810]

[43]
Bruaene CV, De Looze D, Hindryckx P. Small bowel capsule endoscopy: Where are we after almost 15 years of use? World J Gastrointest Endosc  2015; 7(1): 13-36.
 [http://dx.doi.org/10.4253/wjge.v7.i1.13] [PMID:  25610531]

[44]
Oh DJ, Kim KS, Lim YJ. A new active locomotion capsule endoscopy under magnetic control and automated reading program. Clin Endosc  2020; 53(4): 395-401.
 [http://dx.doi.org/10.5946/ce.2020.127] [PMID:  32746536]

[45]
Becker D, Zhang J, Heimbach T, et al. Novel orally swallowable IntelliCap(®) device to quantify regional drug absorption in human GI tract using diltiazem as model drug. AAPS PharmSciTech  2014; 15(6): 1490-7.
 [http://dx.doi.org/10.1208/s12249-014-0172-1] [PMID:  25023947]

[46]
Cortegoso Valdivia P, Robertson AR, De Boer NKH, Marlicz W, Koulaouzidis A. An overview of robotic capsules for drug delivery to the gastrointestinal tract. J Clin Med  2021; 10(24): 5791.
 [http://dx.doi.org/10.3390/jcm10245791] [PMID:  34945087]

[47]
Lawenko RMA, Lee YY. Evaluation of gastroesophageal reflux disease using the bravo capsule pH system. J Neurogastroenterol Motil  2015; 22(1): 25-30.
 [http://dx.doi.org/10.5056/jnm15151] [PMID:  26717929]

[48]
Enns C, Galorport C, Ou G, Enns R. Assessment of capsule endoscopy utilizing capsocam plus in patients with suspected small bowel disease including pilot study with remote access patients during pandemic. J Can Assoc Gastroenterol  2021; 4(6): 269-73.
 [http://dx.doi.org/10.1093/jcag/gwaa042] [PMID:  34988365]

[49]
Miyazu T, Osawa S, Tamura S, et al. Modified method of patency judgement using patency capsule prior to capsule endoscopy in clinical practice. Sci Rep  2022; 12(1): 14335.
 [http://dx.doi.org/10.1038/s41598-022-18569-y] [PMID:  35995963]

[50]
Xu Y, Zhang W, Ye S, et al. The evaluation of the OMOM capsule endoscopy with similar pictures elimination mode. Clin Res Hepatol Gastroenterol  2014; 38(6): 757-62.
 [http://dx.doi.org/10.1016/j.clinre.2014.05.009] [PMID:  25282556]

[51]
Shamsudhin N, Zverev VI, Keller H, et al. Magnetically guided capsule endoscopy. Med Phys  2017; 44(8): e91-e111.
 [http://dx.doi.org/10.1002/mp.12299] [PMID:  28437000]

[52]
Angle TC, Gillette RL. Telemetric measurement of body core temperature in exercising unconditioned Labrador retrievers. Can J Vet Res  2011; 75(2): 157-9.
 [PMID:  21731189]

[53]
Kalantar-zadeh K, Ha N, Ou JZ, Berean KJ. Ingestible sensors. ACS Sens  2017; 2(4): 468-83.
 [http://dx.doi.org/10.1021/acssensors.7b00045] [PMID:  28723186]

[54]
Sehyuk Yim, Gultepe E, Gracias DH, Sitti M. Biopsy using a magnetic capsule endoscope carrying, releasing, and retrieving untethered microgrippers. IEEE Trans Biomed Eng  2014; 61(2): 513-21.
 [http://dx.doi.org/10.1109/TBME.2013.2283369] [PMID:  24108454]

[55]
Kyoungchul K, Jinhoon C, Doyoung J, Dong-il C. A rotational micro biopsy device for the capsule endoscope. Proceedings of the IEEE/RSJ international conference on intelligent robots and systems. 1839-43.

[56]
Singeap AM, Stanciu C, Trifan A. Capsule endoscopy: The road ahead. World J Gastroenterol  2016; 22(1): 369-78.
 [http://dx.doi.org/10.3748/wjg.v22.i1.369] [PMID:  26755883]

[57]
Jarow JP, Baxley JH. Medical devices: US medical device regulation. Urol Oncol  2015; 33(3): 128-32.
 [http://dx.doi.org/10.1016/j.urolonc.2014.10.004] [PMID:  25458071]

[58]
French-Mowat E, Burnett J. How are medical devices regulated in the European Union? J R Soc Med  2012; 105 (Suppl. 1): S22-8.

[59]
Tcheng JE, Nguyen MV, Brann HW, et al. The medical device unique device identifier as the single source of truth in healthcare enterprises – roadmap for implementation of the clinically integrated supply chain. Med Devices  2021; 14: 459-67.
 [http://dx.doi.org/10.2147/MDER.S344132] [PMID:  34992475]

[60]
Institute of medicine (US) committee on accelerating rare diseases research and orphan product development: Rare diseases and orphan products: Accelerating research and development. Field mj, Boat tf, Eds. Medical Devices: Research and Development for Rare Diseases. Washington (DC): : National Academies Press (US) 2010; 7.

[61]
Kheir O, Smedts S, Jacoby A, Verwulgen S. Efficient quality management in medtech start-ups (Based on ISO 13485). Med Devices  2021; 14: 313-9.
 [http://dx.doi.org/10.2147/MDER.S320583] [PMID:  34703329]

[62]
Cohen G, Gerke S, Kramer DB. Ethical and legal implications of remote monitoring of medical devices. Milbank Q  2020; 98(4): 1257-89.
 [http://dx.doi.org/10.1111/1468-0009.12481] [PMID:  33078879]

[63]
Baisakhiya S, Ganeasn R, Das SK. IEC 60601-1-2,2001: New EMC requirements for medical equipment 8th International Conference on Electromagnetic Interference and Compatibility. Chennai, India  2003; pp. 409-14.
 [http://dx.doi.org/10.1109/ICEMIC.2003.238092]

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DOI https://dx.doi.org/10.2174/0126673878265457231205114925	Print ISSN 2667-3878
Publisher Name Bentham Science Publisher	Online ISSN 2667-3886

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Robotic Pills as Innovative Personalized Medicine Tools: A Mini Review

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