Bridging the Gap: Investigating the State-of-the-Art Approaches in Oral Biologic Delivery and Their Role in Redefining Therapeutic Possibilities
DOI:
https://doi.org/10.22270/ijmspr.v10i4.100Keywords:
Biologics, intestinal mucosa, permeability, oral delivery, gastrointestinal tract, macromoleculesAbstract
Biopharmaceutical medications that originate from biological sources and processes are known as biologics. Biologics are now the most promising medications for oral use in treating a variety of illnesses. These illnesses may involve problems with inflammation and metabolism. It has been established that the most practical way to provide medication is by oral delivery of biologics. Due to the simplicity of taking doses, patients are observed to be directed towards the oral drug, demonstrating its great effectiveness. Even though biologicals are the most promising medicine, oral delivery of these drugs still faces numerous challenges because of a number of extremely strict limitations. The two major obstacles are the sensitivity and the difficulty of delivering the biologics through the gastrointestinal tract. Because oral administration of biologicals has been shown to be crucial for achieving the desired long-term effects from the treatment, it is the most researched topic and continues to attract the attention of several researchers. Since it is more convenient for patients, taking medications orally is preferred; however, biologics cannot currently be administered orally. Multiple barriers are present in the gastrointestinal tract due to its physiological role, which restricts the absorption of complex macromolecules into the body after intake. Because biologics are relatively large molecules, they have very limited permeability across the intestinal mucosa in addition to being exceedingly vulnerable to the harsh environment of the digestive tract. The history of research on oral delivery of biologics is extensive, and the recent surge in biologics has further intensified this body of work. The primary physiological obstacles to oral biologic delivery are outlined in this article along with many research approaches that may be used to facilitate or enhance oral biological delivery.
Keywords: Biologics, intestinal mucosa, permeability, oral delivery, gastrointestinal tract, macromolecules
References
New R, "Oral Delivery of Biologics via the Intestine," Pharmaceutics, vol. 13, no. 1, p. 18, Dec. 2020. https://doi.org/10.3390/pharmaceutics13010018
Urquhart L. Top drugs and companies by sales in 2018. Nat Rev Drug Discov 2019;18(245). https://doi.org/10.1038/d41573-019-00049-0
Gedawy A, Martinez J, Al-Salami H & Dass CR. Oral insulin delivery: existing barriers and current counter-strategies. J Pharm Pharmacol 2018;70(2):197-213. https://doi.org/10.1111/jphp.12852
Liang, F.; Loré, K. Local innate immune responses in the vaccine adjuvant-injected muscle. Clin. Transl. Immunol. 2016, 5, 74-81. https://doi.org/10.1038/cti.2016.19
Herzog, R.W.; Hagstrom, J.N.; Kung, S.H.; Tai, S.J.; Wilson, J.M.; Fisher, K.J.; High, K.A. Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus. Proc. Natl. Acad. Sci. USA 1997, 94, 5804-5809. https://doi.org/10.1073/pnas.94.11.5804
Nanaki, S.; Siafaka, P.I.; Zachariadou, D.; Nerantzaki, M.; Giliopoulos, D.J.; Triantafyllidis, K.S.; Kostoglou, M.; Nikolakaki, E.; Bikiaris, D.N. PLGA/SBA-15 mesoporous silica composite microparticles loaded with paclitaxel for local chemotherapy. Eur. J. Pharm. Sci. 2017, 99, 32-44. https://doi.org/10.1016/j.ejps.2016.12.010
Moeller, E.H.; Jorgensen, L. Alternative routes of administration for systemic delivery of protein pharmaceuticals. Drug Discov. Today Technol. 2008, 5, 89-94. https://doi.org/10.1016/j.ddtec.2008.11.005
9.Kale, T.R. Needle free injection technology-An overview. Inov. Pharm. 2014, 5, 1-8. https://doi.org/10.24926/iip.v5i1.330
A. C. Anselmo, Y. Gokarn, and S. Mitragotri, "Non-invasive Delivery Strategies for Biologics," Nature Reviews Drug Discovery, vol. 18, no. 1, pp. 19-40, Nov. 2018. https://doi.org/10.1038/nrd.2018.183
Khanvilkar K, Donovan MD & Flanagan DR. Drug transfer through mucus. Adv Drug Deliv Rev 2001;48(2-3):173-193. https://doi.org/10.1016/S0169-409X(01)00115-6
Mantaj J, Abu-Shams T, Enlo-Scott Z et al. Role of the basement membrane as an intestinal barrier to absorption of macromolecules and nanoparticles. Mol Pharm 2018;15(12):5802-5808. https://doi.org/10.1021/acs.molpharmaceut.8b01053
13 Vllasaliu D, Falcone FH, Stolnik S & Garnett M. Basement membrane influences intestinal epithelial cell growth and presents a barrier to the movement of macromolecules. Exp Cell Res 2014;323(1):218-231. https://doi.org/10.1016/j.yexcr.2014.02.022
Mahato RI, Narang AS, Thoma L & Miller DD. Emerging trends in oral delivery of peptide and protein drugs. Crit Rev Ther Drug Carrier Syst 2003;20(2-3):153-214. https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v20.i23.30
Maher S, Ryan B, Duffy A & Brayden DJ. Formulation strategies to improve oral peptide delivery. Pharm Pat Anal 2014;3(3):313-336. https://doi.org/10.4155/ppa.14.1
Bruno BJ, Miller GD & Lim CS. Basics and recent advances in peptide and protein drug delivery. Ther Deliv 2013;4(11):1443-1467. https://doi.org/10.4155/tde.13.104
Crowe JS, Roberts KJ, Carlton TM et al. Preclinical development of a novel, orally-administered anti-tumour necrosis factor domain antibody for the treatment of inflammatory bowel disease. Sci Rep 2018;8(1):4941. https://doi.org/10.1038/s41598-018-23277-7
Bernkop-Schnürch A. Mucoadhesive systems in oral drug delivery. Drug Discov Today Technol 2005;2(1):83-87. https://doi.org/10.1016/j.ddtec.2005.05.001
Homayun B, Lin X & Choi HJ. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals. Pharmaceutics 2019;11(3):129. https://doi.org/10.3390/pharmaceutics11030129
Gupta V, Hwang BH, Lee J et al. Mucoadhesive intestinal devices for oral delivery of salmon calcitonin. J Control Release 2013;172(3):753-762. https://doi.org/10.1016/j.jconrel.2013.09.004
Gupta V, Hwang BH, Doshi N et al. Delivery of exenatide and insulin using mucoadhesive intestinal devices. Ann Biomed Eng 2016;44(6):1993-2007. https://doi.org/10.1007/s10439-016-1558-x
Homayun B, Lin X & Choi HJ. Challenges and recent progress in oral drug delivery systems for biopharmaceuticals. Pharmaceutics 2019;11(3):129. https://doi.org/10.3390/pharmaceutics11030129
. Vllasaliu D, Thanou M, Stolnik S & Fowler R. Recent advances in oral delivery of biologics: nanomedicine and physical modes of delivery. Expert Opin Drug Deliv 2018;15(8): 759-770. https://doi.org/10.1080/17425247.2018.1504017
Anderberg EK, Nystrom C & Artursson P. Epithelial transport of drugs in cell culture. VII: Effects of pharmaceutical surfactant excipients and bile acids on transepithelial permeability in monolayers of human intestinal epithelial (Caco-2) cells. J Pharm Sci 1992;81(9):879-887. https://doi.org/10.1002/jps.2600810908
McCartney F, Gleeson JP & Brayden DJ. Safety concerns over the use of intestinal permeation enhancers: a mini-review. Tissue Barriers 2016;4(2):e1176822. https://doi.org/10.1080/21688370.2016.1176822
Amet N, Wang W & Shen WC. Human growth hormone-transferrin fusion protein for oral delivery in hypophysectomized rats. J Control Release 2010;141(2):177-182. https://doi.org/10.1016/j.jconrel.2009.09.007
Pridgen EM, Alexis F, Kuo TT et al. Transepithelial transport of Fc-targeted nanoparticles by the neonatal fc receptor for oral delivery. Sci Transl Med 2013;5(213):213ra167. https://doi.org/10.1126/scitranslmed.3007049
Vllasaliu D, Thanou M, Stolnik S & Fowler R. Recent advances in oral delivery of biologics: nanomedicine and physical modes of delivery. Expert Opin Drug Deliv 2018;15(8): 759-770. https://doi.org/10.1080/17425247.2018.1504017
Shi Y, Sun X, Zhang L et al. Fc-modifled exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice. Sci Rep 2018;8(1):726. https://doi.org/10.1038/s41598-018-19170-y
Shen S, Wu Y, Liu Y & Wu D. High drug-loading nanomedicines: progress, current status, and prospects. Int J Nanomedicine 2017;12:4085-4109. https://doi.org/10.2147/IJN.S132780
BioSpace. First human study of "robotic" RaniPill capsule to replace injections announced by Rani Therapeutics. 2019. Available at: https://www.biospace.com/article/releases/flrst-human-study-of-and-quot-robotic-and-quot-ranipill-capsule-to-replace-injections-announced-by-rani-therapeutics/
Traverso G, Schoellhammer CM, Schroeder A et al. Microneedles for drug delivery via the gastrointestinal tract. J Pharm Sci 2015;104(2):362-367. https://doi.org/10.1002/jps.24182
Abramson A, Caffarel-Salvador E, Khang M et al. An ingestible self-orienting system for oral delivery of macromolecules. Science 2019;363(6427):611-615. https://doi.org/10.1126/science.aau2277
Liebowitz D, Lindbloom JD, Brandl JR, Garg SJ, Tucker SN. 2015. High Titre neutralising antibodies to influenza after oral tablet immunisation: a phase 1 ,randomised, placebo-controlled trial. Lancet Infect.Dis. 15(9):1041-48 https://doi.org/10.1016/S1473-3099(15)00266-2
Gurwith M, Lock M, Taylor EM, Ishioka G, Alexander J,et al.2013.Safety and immunogenicity of an oral, replicating adenovirus serotype 4 vector vaccine for H5N1 influenza:a randomised, double-blind, placebo-controlled, phase 1 study. Lancet Infect.Dis.13(3):238-50 https://doi.org/10.1016/S1473-3099(12)70345-6
Abramson A, Caffarel-Salvador E, Khang M et al. An ingestible self-orienting system for oral delivery of macromolecules. Science 2019;363(6427):611-615. https://doi.org/10.1126/science.aau2277
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