Abstract
Background: Due to the lifestyle of people in the community in recent years, the prevalence of diabetes mellitus has increased, so New drugs and related treatments are also being developed.
Introduction: One of the essential treatments for diabetes today is injectable insulin forms, which have their problems and limitations, such as invasive and less admission of patients and high cost of production. According to the mentioned issues, Theoretically, Oral insulin forms can solve many problems of injectable forms.
Methods: Many efforts have been made to design and introduce Oral delivery systems of insulin, such as lipid-based, synthetic polymer-based, and polysaccharide-based nano/microparticle formulations. The present study reviewed these novel formulations and strategies in the past five years and checked their properties and results.
Results: According to peer-reviewed research, insulin-transporting particles may preserve insulin in the acidic and enzymatic medium and decrease peptide degradation; in fact, they could deliver appropriate insulin levels to the intestinal environment and then to blood. Some of the studied systems increase the permeability of insulin to the absorption membrane in cellular models. In most investigations, in vivo results revealed a lower ability of formulations to reduce BGL than subcutaneous form, despite promising results in in vitro and stability testing.
Conclusion: Although taking insulin orally currently seems unfeasible, future systems may be able to overcome mentioned obstacles, making oral insulin delivery feasible and producing acceptable bioavailability and treatment effects in comparison to injection forms.
Graphical Abstract
[http://dx.doi.org/10.1016/S2221-1691(12)60067-7] [PMID: 23569941]
[http://dx.doi.org/10.1007/s12010-009-8871-x] [PMID: 19957208]
[http://dx.doi.org/10.1007/s13300-019-00743-7] [PMID: 31902063]
[http://dx.doi.org/10.1016/j.ijbiomac.2018.08.152] [PMID: 30170057]
[http://dx.doi.org/10.1016/j.addr.2011.12.009] [PMID: 22212900]
[http://dx.doi.org/10.1016/j.apsb.2021.04.001] [PMID: 34522593]
[http://dx.doi.org/10.4103/0250-474X.42967] [PMID: 20046732]
[http://dx.doi.org/10.1080/17425247.2020.1789585] [PMID: 32602795]
[http://dx.doi.org/10.1016/j.ijbiomac.2019.10.233] [PMID: 31794824]
[http://dx.doi.org/10.1021/bm200083n] [PMID: 21388145]
[http://dx.doi.org/10.1016/j.jddst.2019.101250]
[http://dx.doi.org/10.1081/DDC-120003853] [PMID: 12149954]
[http://dx.doi.org/10.1016/j.jconrel.2016.04.012] [PMID: 27074369]
[http://dx.doi.org/10.4103/0250-474X.58165] [PMID: 20502564]
[http://dx.doi.org/10.3390/md18010055] [PMID: 31952203]
[http://dx.doi.org/10.1021/acs.jafc.8b02525] [PMID: 30346766]
[http://dx.doi.org/10.1016/j.bmcl.2016.11.083] [PMID: 27956345]
[http://dx.doi.org/10.1038/nature19764] [PMID: 27734871]
[http://dx.doi.org/10.1038/s41598-017-02014-6] [PMID: 28512335]
[http://dx.doi.org/10.1016/j.xphs.2020.07.004] [PMID: 32663595]
[http://dx.doi.org/10.1016/j.carbpol.2019.115617] [PMID: 31887888]
[http://dx.doi.org/10.1248/bpb.28.1801] [PMID: 16141566]
[http://dx.doi.org/10.3390/molecules24234371] [PMID: 31795385]
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v24.i1.30] [PMID: 17430100]
[http://dx.doi.org/10.1186/s12951-020-00662-x] [PMID: 32711522]
[http://dx.doi.org/10.34172/apb.2020.022] [PMID: 32373486]
[http://dx.doi.org/10.1080/21691401.2018.1511575] [PMID: 30280608]
[http://dx.doi.org/10.1007/s00360-015-0937-1] [PMID: 26510419]
[http://dx.doi.org/10.1080/10717544.2016.1261381] [PMID: 28165858]
[http://dx.doi.org/10.1016/j.jconrel.2020.05.045] [PMID: 32479845]
[http://dx.doi.org/10.1016/j.xphs.2019.04.020] [PMID: 31047941]
[http://dx.doi.org/10.1080/17425247.2016.1178233] [PMID: 27102882]
[http://dx.doi.org/10.1080/10717544.2018.1469685] [PMID: 29791242]
[http://dx.doi.org/10.4155/tde-2019-0010] [PMID: 31789106]
[http://dx.doi.org/10.1039/C4BM00203B] [PMID: 32481954]
[http://dx.doi.org/10.1002/star.202000002]
[http://dx.doi.org/10.1016/j.ijbiomac.2021.06.077] [PMID: 34144062]
[http://dx.doi.org/10.1002/star.201800040]
[http://dx.doi.org/10.1016/j.scitotenv.2021.150213] [PMID: 34571232]
[http://dx.doi.org/10.1016/j.colsurfb.2017.07.044] [PMID: 28750341]
[http://dx.doi.org/10.1039/D1FO01411K] [PMID: 34606530]
[http://dx.doi.org/10.1016/j.gaost.2022.01.001]
[http://dx.doi.org/10.1016/j.carbpol.2013.02.021] [PMID: 23618232]
[http://dx.doi.org/10.5001/omj.2010.24] [PMID: 22125706]
[http://dx.doi.org/10.1016/j.ijpharm.2014.03.038] [PMID: 24657577]
[http://dx.doi.org/10.1016/j.ejpb.2017.11.012] [PMID: 29175551]
[http://dx.doi.org/10.1016/j.enzmictec.2018.06.014] [PMID: 30143195]
[http://dx.doi.org/10.3390/coatings11080922]
[http://dx.doi.org/10.1080/17425247.2016.1182485] [PMID: 27116988]
[http://dx.doi.org/10.3390/pharmaceutics12060533] [PMID: 32531886]
[http://dx.doi.org/10.3390/jfb10010004] [PMID: 30626094]
[http://dx.doi.org/10.1016/j.apsb.2021.02.020] [PMID: 33996411]
[http://dx.doi.org/10.1093/advances/nmy059] [PMID: 30689684]
[http://dx.doi.org/10.1016/j.jddst.2022.103141]
[http://dx.doi.org/10.1016/j.jconrel.2021.11.020] [PMID: 34793919]
[http://dx.doi.org/10.1016/S0142-9612(00)00286-6] [PMID: 11336306]
[http://dx.doi.org/10.1016/j.jconrel.2020.02.034] [PMID: 32097672]
[http://dx.doi.org/10.1016/j.pmatsci.2019.01.001]
[http://dx.doi.org/10.1016/j.actbio.2021.08.046] [PMID: 34487859]
[http://dx.doi.org/10.4155/tde.14.91] [PMID: 25565440]
[http://dx.doi.org/10.1016/j.matdes.2020.108805]
[http://dx.doi.org/10.1007/s00592-015-0714-3] [PMID: 25655131]
[http://dx.doi.org/10.1002/ddr.21545] [PMID: 31140629]
[http://dx.doi.org/10.1016/j.abb.2020.108485] [PMID: 32712288]
[http://dx.doi.org/10.2217/nnm-2017-0372] [PMID: 30338724]
[http://dx.doi.org/10.3390/pharmaceutics13040500] [PMID: 33917577]
[http://dx.doi.org/10.1016/S0378-5173(02)00483-0] [PMID: 12433441]
[http://dx.doi.org/10.3390/pharmaceutics13040541] [PMID: 33924355]
[http://dx.doi.org/10.1016/j.jconrel.2017.05.028] [PMID: 28536049]
[http://dx.doi.org/10.1002/slct.202004210]
[http://dx.doi.org/10.2174/1381612825666190425163424] [PMID: 31465282]
[http://dx.doi.org/10.1016/j.eurpolymj.2018.04.039]
[http://dx.doi.org/10.1016/B978-0-12-814031-4.00003-9]
[http://dx.doi.org/10.3390/pharmaceutics10030074] [PMID: 29937483]
[http://dx.doi.org/10.1016/j.ijpharm.2018.02.038] [PMID: 29476783]
[http://dx.doi.org/10.2147/IJN.S215941] [PMID: 31616141]
[http://dx.doi.org/10.1208/s12248-012-9339-4] [PMID: 22407288]
[http://dx.doi.org/10.1016/j.jddst.2019.02.017]
[http://dx.doi.org/10.1016/j.numecd.2020.09.020] [PMID: 33131992]
[http://dx.doi.org/10.3390/pharmaceutics13040437] [PMID: 33804945]
[http://dx.doi.org/10.1016/j.ejps.2012.05.010] [PMID: 22664358]
[http://dx.doi.org/10.5530/ijper.55.2.76]
[http://dx.doi.org/10.1007/s13346-021-00963-0] [PMID: 33761101]
[http://dx.doi.org/10.1016/j.carbon.2021.02.091]
[http://dx.doi.org/10.1016/j.nbt.2020.10.003] [PMID: 33068793]
[http://dx.doi.org/10.1002/mame.202000799]
[http://dx.doi.org/10.1039/D1TB00645B] [PMID: 34018540]
[http://dx.doi.org/10.1080/17425247.2018.1420050] [PMID: 29257904]
[http://dx.doi.org/10.1080/10837450.2020.1849282] [PMID: 33183103]
[http://dx.doi.org/10.1016/j.ijpharm.2021.120571] [PMID: 33812967]
[http://dx.doi.org/10.1186/s12951-020-00657-8] [PMID: 32680576]
[http://dx.doi.org/10.1016/j.jconrel.2011.12.012] [PMID: 22285551]
[http://dx.doi.org/10.1016/j.jconrel.2021.02.031] [PMID: 33652113]
[http://dx.doi.org/10.1007/s13346-021-00920-x] [PMID: 33575972]
[http://dx.doi.org/10.1016/j.jconrel.2021.08.013] [PMID: 34384795]
[http://dx.doi.org/10.1016/B978-0-12-814031-4.00006-4]
[http://dx.doi.org/10.1016/j.ejps.2020.105272] [PMID: 32084584]