Development of an Insulin Nano-delivery System through Buccal Administration

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Abstract

Aim: The aim of the study was to develop a new nano-delivery system for buccal administration of insulin.

Background: Biodegradable polymeric nanoparticles (PNPs) had undergone countless breakthroughs in drug delivery systems. The main objective of PNPs application in delivering and carrying different promising drugs is to make sure that the drugs are being delivered to their action sites, maximizing the desired effect and overcoming their limitations and drawbacks.

Objective: The main goals of this study were to produce an insulin consumable nano-delivery system for buccal administration and enhance the mucoadhesive effect in sustaining insulin release.

Methods: Water-oil-water (W-O-W) microemulsion solvent evaporation technique was used for the preparation of nanoparticles consisting of positively charged poly (D, L-lactide-co-glycolide) coated with chitosan and loaded with insulin. Later, a consumable buccal film was prepared by the spin coating method and loaded with the previously prepared nanoparticles.

Results: The newly prepared nanoparticle was assessed in terms of size, charge and surface morphology using a Scanning Electron Microscope (SEM), zeta potential, Atomic Force Microscope (AFM), and Fourier Transform Infra-red (FTIR) spectroscopy. An in vitro investigation of the insulin release from nanoparticles and buccal film demonstrated controlled as well as sustained delivery over 6 hrs. The cumulative insulin release decreased to about 28.9% with buccal film compared to the nanoparticle (50%).

Conclusion: The buccal film acted as a barrier for insulin release. Therefore, the release was sustained.

Keywords: Insulin, buccal administration, chitosan, poly (lactic-co-glycolic acid), bioadhesion, w-o-w microemulsion, nanoparticles.

Graphical Abstract

[1]
Chan, J.M.; Valencia, P.M.; Zhang, L.; Langer, R.; Farokhzad, O.C. Polymeric nanoparticles for drug delivery. Methods Mol. Biol., 2010, 624, 163-175.
[http://dx.doi.org/10.1007/978-1-60761-609-2_11] [PMID: 20217595]
[2]
Begines, B.; Ortiz, T.; Pérez-Aranda, M.; Martínez, G.; Merinero, M.; Argüelles-Arias, F.; Alcudia, A. Polymeric nanoparticles for drug delivery: recent developments and future prospects. Nanomaterials (Basel), 2020, 10(7), 1403-1441.
[http://dx.doi.org/10.3390/nano10071403] [PMID: 32707641]
[3]
Bolhassani, A.; Javanzad, S.; Saleh, T.; Hashemi, M.; Aghasadeghi, M.R.; Sadat, S.M. Polymeric nanoparticles: potent vectors for vaccine delivery targeting cancer and infectious diseases. Hum. Vaccin. Immunother., 2014, 10(2), 321-332.
[http://dx.doi.org/10.4161/hv.26796] [PMID: 24128651]
[4]
Zielińska, A.; Carreiró, F.; Oliveira, A.M.; Neves, A.; Pires, B.; Venkatesh, D.N.; Durazzo, A.; Lucarini, M.; Eder, P.; Silva, A.M.; Santini, A.; Souto, E.B. Polymeric nanoparticles: production, characterization, toxicology and ecotoxicology. Molecules, 2020, 25(16), 3731-3751.
[http://dx.doi.org/10.3390/molecules25163731] [PMID: 32824172]
[5]
El-Say, K.M.; El-Sawy, H.S. Polymeric nanoparticles: Promising platform for drug delivery. Int. J. Pharm., 2017, 528(1-2), 675-691.
[http://dx.doi.org/10.1016/j.ijpharm.2017.06.052] [PMID: 28629982]
[6]
Hines, D.J.; Kaplan, D.L. Poly(lactic-co-glycolic) acid-controlled-release systems: experimental and modeling insights. Crit. Rev. Ther. Drug Carrier Syst., 2013, 30(3), 257-276.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2013006475] [PMID: 23614648]
[7]
Croll, T.I.; O’Connor, A.J.; Stevens, G.W.; Cooper-White, J.J. Controllable surface modification of poly(lactic-co-glycolic acid) (PLGA) by hydrolysis or aminolysis I: physical, chemical, and theoretical aspects. Biomacromolecules, 2004, 5(2), 463-473.
[http://dx.doi.org/10.1021/bm0343040] [PMID: 15003007]
[8]
Yurtdaş-Kırımlıoglu, G.; Gorgulu, S. Surface modification of PLGA nanoparticles with chitosan or Eudragit® RS 100: characterization, prolonged release, cytotoxicity, and enhanced antimicrobial activity. J. Drug Deliv. Sci. Technol., 2021, 61, 102145.
[http://dx.doi.org/10.1016/j.jddst.2020.102145]
[9]
Wang, M.; Zhang, Y.; Feng, J.; Gu, T.; Dong, Q.; Yang, X.; Sun, Y.; Wu, Y.; Chen, Y.; Kong, W. Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4. Int. J. Nanomed., 2013, 8, 1141-1154.
[PMID: 23658482]
[10]
Alshetaili, A.S. Gefitinib loaded PLGA and chitosan coated PLGA nanoparticles with magnified cytotoxicity against A549 lung cancer cell lines. Saudi J. Biol. Sci., 2021, 28(9), 5065-5073.
[http://dx.doi.org/10.1016/j.sjbs.2021.05.025] [PMID: 34466084]
[11]
Wang, J.; Li, J.; Ren, J. Surface modification of poly(lactic-co-glycolic acid) microspheres with enhanced hydrophilicity and dispersibility for arterial embolization. Materials (Basel), 2019, 12(12), 1959-1970.
[http://dx.doi.org/10.3390/ma12121959] [PMID: 31216635]
[12]
Ward, P.D.; Tippin, T.K.; Thakker, D.R. Enhancing paracellular permeability by modulating epithelial tight junctions. Pharm. Sci. Technol. Today, 2000, 3(10), 346-358.
[http://dx.doi.org/10.1016/S1461-5347(00)00302-3] [PMID: 11050459]
[13]
Lang, X.; Wang, T.; Sun, M.; Chen, X.; Liu, Y. Advances and applications of chitosan-based nanomaterials as oral delivery carriers: A review. Int. J. Biol. Macromol., 2020, 154, 433-445.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.03.148] [PMID: 32194103]
[14]
Sogias, I.A.; Williams, A.C.; Khutoryanskiy, V.V. Why is chitosan mucoadhesive? Biomacromolecules, 2008, 9(7), 1837-1842.
[http://dx.doi.org/10.1021/bm800276d] [PMID: 18540644]
[15]
Abouhussein, D.; El Nabarawi, M.A.; Shalaby, S.H.; Abd El-Bary, A. Cetylpyridinium chloride chitosan blended mucoadhesive buccal films for treatment of pediatric oral diseases. J. Drug Deliv. Sci. Technol., 2020, 57, 101676.
[http://dx.doi.org/10.1016/j.jddst.2020.101676]
[16]
Li, D.; Fu, D.; Kang, H.; Rong, G.; Jin, Z.; Wang, X.; Zhao, K. Advances and potential applications of chitosan nanoparticles as a delivery carrier for the mucosal immunity of vaccine. Curr. Drug Deliv., 2017, 14(1), 27-35.
[http://dx.doi.org/10.2174/1567201813666160804121123] [PMID: 27494157]
[17]
van der Lubben, I.M.; Verhoef, J.C.; Borchard, G.; Junginger, H.E. Chitosan and its derivatives in mucosal drug and vaccine delivery. Eur. J. Pharm. Sci., 2001, 14(3), 201-207.
[http://dx.doi.org/10.1016/S0928-0987(01)00172-5] [PMID: 11576824]
[18]
Pardeshi, C.V.; Belgamwar, V.S. Improved brain pharmacokinetics following intranasal administration of N,N,N-trimethyl chitosan tailored mucoadhesive NLCs. Mater. Tech., 2019, 35, 1-18.
[19]
Sorli, C.; Heile, M.K. Identifying and meeting the challenges of insulin therapy in type 2 diabetes. J. Multidiscip. Healthc., 2014, 7, 267-282.
[20]
Forst, T.; Choudhary, P.; Schneider, D.; Linetzky, B.; Pozzilli, P. A practical approach to the clinical challenges in initiation of basal insulin therapy in people with type 2 diabetes. Diabetes Metab. Res. Rev., 2021, 37(6), e3418.
[http://dx.doi.org/10.1002/dmrr.3418] [PMID: 33098260]
[21]
Chen, J.W.; Christiansen, J.S.; Lauritzen, T. Limitations to subcutaneous insulin administration in type 1 diabetes. Diabetes Obes. Metab., 2003, 5(4), 223-233.
[http://dx.doi.org/10.1046/j.1463-1326.2003.00266.x] [PMID: 12795655]
[22]
Choudhary, P.; Amiel, S.A. Hypoglycaemia in type 1 diabetes: technological treatments, their limitations and the place of psychology. Diabetologia, 2018, 61(4), 761-769.
[http://dx.doi.org/10.1007/s00125-018-4566-6] [PMID: 29423581]
[23]
Holpuch, A.S.; Hummel, G.J.; Tong, M.; Seghi, G.A.; Pei, P.; Ma, P.; Mumper, R.J.; Mallery, S.R. Nanoparticles for local drug delivery to the oral mucosa: proof of principle studies. Pharm. Res., 2010, 27(7), 1224-1236.
[http://dx.doi.org/10.1007/s11095-010-0121-y] [PMID: 20354767]
[24]
Pawar, R.R.; Raut, D.B.; Karde, V.K.; Wadikar, J.C.; Jadhav, A.S.; Chintale, A.G. Mucoadhesive buccal drug delivery system: A review. Res. J. Pharm. Technol., 2013, 6, 506-515.
[25]
Shirvan, A.R.; Bashari, A.; Hemmatinejad, N. New Insight into the Fabrication of Smart Mucoadhesive Buccal Patches as a Novel Controlled-Drug Delivery System. Eur. Polym. J., 2019, 119, 541-550.
[http://dx.doi.org/10.1016/j.eurpolymj.2019.07.010]
[26]
Ramesh, B.; Saravanakumar, K.; Nagaveni, P.; Mohan Kumar, A.; Jaya Preethi, P.; Vivek Kumar, P. A review on buccal drug delivery system. Int. J. Res. Pharm. Sci., 2014, 5, 200-204.
[27]
Fonseca-Santos, B.; Chorilli, M. An overview of polymeric dosage forms in buccal drug delivery: State of art, design of formulations and their in vivo performance evaluation. Mater. Sci. Eng. C, 2018, 86, 129-143.
[http://dx.doi.org/10.1016/j.msec.2017.12.022] [PMID: 29525088]
[28]
Giovino, C.; Ayensu, I.; Tetteh, J.; Boateng, J.S. Development and characterisation of chitosan films impregnated with insulin loaded PEG-b-PLA nanoparticles (NPs): a potential approach for buccal delivery of macromolecules. Int. J. Pharm., 2012, 428(1-2), 143-151.
[http://dx.doi.org/10.1016/j.ijpharm.2012.02.035] [PMID: 22405987]
[29]
Mahdizadeh Barzoki, Z.; Emam-Djomeh, Z.; Mortazavian, E.; Akbar Moosavi-Movahedi, A.; Rafiee, T.M. Formulation, in vitro evaluation and kinetic analysis of chitosan-gelatin bilayer muco-adhesive buccal patches of insulin nanoparticles. J. Microencapsul., 2016, 33(7), 613-624.
[http://dx.doi.org/10.1080/02652048.2016.1234513] [PMID: 27606816]
[30]
Mortazavian, E.; Dorkoosh, F.A.; Rafiee-Tehrani, M. Design, characterization and ex vivo evaluation of chitosan film integrating of insulin nanoparticles composed of thiolated chitosan derivative for buccal delivery of insulin. Drug Dev. Ind. Pharm., 2014, 40(5), 691-698.
[http://dx.doi.org/10.3109/03639045.2014.886590] [PMID: 24524272]
[31]
Hinds, K.D.; Campbell, K.M.; Holland, K.M.; Lewis, D.H.; Piché, C.A.; Schmidt, P.G. PEGylated insulin in PLGA microparticles. In vivo and in vitro analysis. J. Control. Release, 2005, 104(3), 447-460.
[http://dx.doi.org/10.1016/j.jconrel.2005.02.020] [PMID: 15911045]
[32]
Liu, T.; Wang, Y.; Zhong, W.; Li, B.; Mequanint, K.; Luo, G.; Xing, M. Biomedical applications of layer-by-layer self assembly for cell encapsulation: current status and future perspectives. Adv. Healthc. Mater., 2019, 8(1), e1800939.
[http://dx.doi.org/10.1002/adhm.201800939] [PMID: 30511822]
[33]
Chinna Reddy, P.; Chaitanya, K.S.C.; Madhusudan, R.Y. A review on bioadhesive buccal drug delivery systems: current status of formulation and evaluation methods. Daru, 2011, 19(6), 385-403.
[PMID: 23008684]
[34]
Chokshi, R.; Zia, H. Hot-melt extrusion technique: A review. IJPR, 2004, 3, 3-16.
[35]
Moreira, J.; Vale, A.C.; Alves, N.M. Spin-coated freestanding films for biomedical applications. J. Mater. Chem. B Mater. Biol. Med., 2021, 9(18), 3778-3799.
[http://dx.doi.org/10.1039/D1TB00233C] [PMID: 33876170]
[36]
Zhang, X.; Sun, M.; Zheng, A.; Cao, D.; Bi, Y.; Sun, J. Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration. Eur. J. Pharm. Sci., 2012, 45(5), 632-638.
[http://dx.doi.org/10.1016/j.ejps.2012.01.002] [PMID: 22248882]
[37]
Chen, H.; Xie, L.Q.; Qin, J.; Jia, Y.; Cai, X.; Nan, W.; Yang, W.; Lv, F.; Zhang, Q.Q. Surface modification of PLGA nanoparticles with biotinylated chitosan for the sustained in vitro release and the enhanced cytotoxicity of epirubicin. Colloids Surf. B Biointerfaces, 2016, 138, 1-9.
[http://dx.doi.org/10.1016/j.colsurfb.2015.11.033] [PMID: 26638176]
[38]
Shi, Y.; Xue, J.; Jia, L.; Du, Q.; Niu, J.; Zhang, D. Surface-modified PLGA nanoparticles with chitosan for oral delivery of tolbutamide. Colloids Surf. B Biointerfaces, 2018, 161, 67-72.
[http://dx.doi.org/10.1016/j.colsurfb.2017.10.037] [PMID: 29040836]
[39]
Patel, D.A.; Patel, M.R.; Patel, K.R.; Patel, N.M. Buccal mucosa as a route for systemic drug delivery: A review. Int. J. Drug Dev. Res., 2012, 4, 99-116.
[40]
Silva, M.M.; Calado, R.; Marto, J.; Bettencourt, A.; Almeida, A.J.; Gonçalves, L.M.D. Chitosan nanoparticles as a mucoadhesive drug delivery system for ocular administration. Mar. Drugs, 2017, 15(12), 370-382.
[http://dx.doi.org/10.3390/md15120370] [PMID: 29194378]
[41]
Chaiyasan, W.; Srinivas, S.P.; Tiyaboonchai, W. Mucoadhesive chitosan-dextran sulfate nanoparticles for sustained drug delivery to the ocular surface. J. Ocul. Pharmacol. Ther., 2013, 29(2), 200-207.
[http://dx.doi.org/10.1089/jop.2012.0193] [PMID: 23356788]
[42]
Chaves, P.D.; Ourique, A.F.; Frank, L.A.; Pohlmann, A.R.; Guterres, S.S.; Beck, R.C. Carvedilol-loaded nanocapsules: Mucoadhesive properties and permeability across the sublingual mucosa. Eur. J. Pharm. Biopharm., 2017, 114, 88-95.
[http://dx.doi.org/10.1016/j.ejpb.2017.01.007] [PMID: 28119104]
[43]
Yan, S.; Zhu, J.; Wang, Z.; Yin, J.; Zheng, Y.; Chen, X. Layer-by-layer assembly of poly(L-glutamic acid)/chitosan microcapsules for high loading and sustained release of 5-fluorouracil. Eur. J. Pharm. Biopharm., 2011, 78(3), 336-345.
[http://dx.doi.org/10.1016/j.ejpb.2010.12.031] [PMID: 21195174]
[44]
Tamburaci, S.; Tihminlioglu, F. Diatomite reinforced chitosan composite membrane as potential scaffold for guided bone regeneration. Mater. Sci. Eng. C, 2017, 80, 222-231.
[http://dx.doi.org/10.1016/j.msec.2017.05.069] [PMID: 28866160]
[45]
Ratih, D.N.; Enggardipta, R.A.; Kartikaningtyas, A.T. The effect of chitosan nanoparticle as A final irrigation solution on the smear layer removal, micro-hardness and surface roughness of root canal dentin. Open Dent. J., 2020, 14, 19-26.
[http://dx.doi.org/10.2174/1874210602014010019]
[46]
Miyata, T.; Masuko, T. Crystallization behaviour of poly(L-lactide). Polymer (Guildf.), 1998, 39, 5515-5521.
[http://dx.doi.org/10.1016/S0032-3861(97)10203-8]
[47]
Fernandes Queiroz, M.; Melo, K.R.; Sabry, D.A.; Sassaki, G.L.; Rocha, H.A. Does the use of chitosan contribute to oxalate kidney stone formation? Mar. Drugs, 2014, 13(1), 141-158.
[http://dx.doi.org/10.3390/md13010141] [PMID: 25551781]
[48]
Zhao, K.; Zhang, Y.; Zhang, X.; Shi, C.; Wang, X.; Wang, X.; Jin, Z.; Cui, S. Chitosan-coated poly(lactic-co-glycolic) acid nanoparticles as an efficient delivery system for Newcastle disease virus DNA vaccine. Int. J. Nanomedicine, 2014, 9, 4609-4619.
[http://dx.doi.org/10.2147/IJN.S70633] [PMID: 25356070]
[49]
Houchin, M.L.; Topp, E.M. Chemical degradation of peptides and proteins in PLGA: a review of reactions and mechanisms. J. Pharmacol. Sci., 2008, 97(7), 2395-2404.
[http://dx.doi.org/10.1002/jps.21176] [PMID: 17828756]
[50]
Fang, Y.; Zhang, N.; Li, Q.; Chen, J.; Xiong, S.; Pan, W. Characterizing the release mechanism of donepezil-loaded PLGA microspheres in vitro and in vivo. J. Drug Deliv. Sci. Technol., 2019, 51, 430-437.
[http://dx.doi.org/10.1016/j.jddst.2019.03.029]
[51]
Anwer, M.K.; Mohammad, M.; Ezzeldin, E.; Fatima, F.; Alalaiwe, A.; Iqbal, M. Preparation of sustained release apremilast-loaded PLGA nanoparticles: In vitro characterization and in vivo pharmacokinetic study in rats. Int. J. Nanomedicine, 2019, 14, 1587-1595.
[http://dx.doi.org/10.2147/IJN.S195048] [PMID: 30880967]
[52]
Abd El Hady, W.E.; Mohamed, E.A.; Soliman, O.A.E.; El-Sabbagh, H.M. In vitro-in vivo evaluation of chitosan-PLGA nanoparticles for potentiated gastric retention and anti-ulcer activity of diosmin. Int. J. Nanomedicine, 2019, 14, 7191-7213.
[http://dx.doi.org/10.2147/IJN.S213836] [PMID: 31564873]
[53]
Fredenberg, S.; Wahlgren, M.; Reslow, M.; Axelsson, A. The mechanisms of drug release in poly(lactic-co-glycolic acid)-based drug delivery systems-a review. Int. J. Pharm., 2011, 415(1-2), 34-52.
[http://dx.doi.org/10.1016/j.ijpharm.2011.05.049] [PMID: 21640806]
[54]
Almoustafa, H.A.; Alshawsh, M.A.; Chik, Z. Technical aspects of preparing PEG-PLGA nanoparticles as carrier for chemotherapeutic ‎agents by nanoprecipitation method. Int. J. Pharm., 2017, 533(1), 275-284.
[http://dx.doi.org/10.1016/j.ijpharm.2017.09.054] [PMID: 28943210]
[55]
Lima, I.A.; Khalil, N.M.; Tominaga, T.T.; Lechanteur, A.; Sarmento, B.; Mainardes, R.M. Mucoadhesive chitosan-coated PLGA nanoparticles for oral delivery of ferulic acid. Artif. Cells Nanomed. Biotechnol., 2018, 46(sup2), 993-1002.
[http://dx.doi.org/10.1080/21691401.2018.1477788] [PMID: 29842790]
[56]
Romainor, A.; Chin, S.; Pang, S.; Maurice Bilung, L. Preparation and characterization of chitosan nanoparticles-doped cellulose films with antimicrobial property. J. Nanomater., 2014, 2014, 1-10.
[http://dx.doi.org/10.1155/2014/710459]
[57]
Salehi, S.; Boddohi, S. New formulation and approach for mucoadhesive buccal film of rizatriptan benzoate. Prog. Biomater., 2017, 6(4), 175-187.
[http://dx.doi.org/10.1007/s40204-017-0077-7] [PMID: 29110144]
[58]
Alopaeus, J.F.; Hellfritzsch, M.; Gutowski, T.; Scherließ, R.; Almeida, A.; Sarmento, B.; Škalko-Basnet, N.; Tho, I. Mucoadhesive buccal films based on a graft co-polymer - A mucin-retentive hydrogel scaffold. Eur. J. Pharm. Sci., 2020, 142, 105142.
[http://dx.doi.org/10.1016/j.ejps.2019.105142] [PMID: 31707042]
[59]
Semalty, M.; Semalty, A.; Kumar, G. Formulation and characterization of mucoadhesive buccal films of glipizide. Indian J. Pharm. Sci., 2008, 70(1), 43-48.
[http://dx.doi.org/10.4103/0250-474X.40330] [PMID: 20390079]