The Impact of Natural and Synthetic Polymers in Formulating Micro and Nanoparticles for Anti-Diabetic Drugs

Author(s): Nihad Al-hashimi, Mai Babenko, Maria Saaed, Negeen Kargar, Amr ElShaer*

Journal Name: Current Drug Delivery

Volume 18 , Issue 3 , 2021

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Diabetes mellitus is one of the long-known chronic diseases. Today, over 400 million people have been diagnosed with diabetes, yet curing it is still a challenge. Over the decades, the approaches of treating diabetes mellitus have evolved and polymeric materials have played an integral part in developing and manufacturing anti-diabetic medications. However, injection of insulin remains a conventional therapy for the treatment of diabetes. Oral administration is generally the most preferred route; yet, physiological barriers lead to a challenge in the formulation development for oral delivery of antidiabetic peptide and protein drugs. This present review focuses on the role of different types of biodegradable polymers (e.g., synthetic and natural) that have been used to develop micro and nanoparticles based formulations for anti-diabetic drugs (Type 1 and Type 2) and how the various encapsulation strategies impact its therapeutic effect, including pharmacokinetics studies, drug release profiles, and efficacy of the encapsulated drugs. This review also includes studies of different dosage forms such as oral, nasal, inhalation, and sublingual for the treatment of diabetes that have been investigated using synthetic and natural biodegradable polymers in order to develop an alternative route to subcutaneous route for better control of serum glucose levels.

Keywords: Diabetes mellitus, microparticles, nanoparticles, pharmacokinetics, polymers, biodegradable.

WHO. Gloabl report on diabetes; WHO Press: France, 2016, p. 83.
Hamman, R.F.; Bell, R.A.; Dabelea, D.; D’Agostino, R.B., Jr; Dolan, L.; Imperatore, G.; Lawrence, J.M.; Linder, B.; Marcovina, S.M.; Mayer-Davis, E.J.; Pihoker, C.; Rodriguez, B.L.; Saydah, S. SEARCH for diabetes in youth study group. The SEARCH for diabetes in youth study: rationale, findings, and future directions. Diabetes Care, 2014, 37(12), 3336-3344.
[ ] [PMID: 25414389]
Ugalmugle, S. Antidiabetics market size industry share analysis report 2018-2024. Industry ARC 2020. https://www.gminsights. com/industry-analysis/antidiabetics-market[Jan 22, 2020]
Sheikh, H.A.; Sapin, A.; Damgé, C.; Leroy, P.; Socha, M.; Maincent, P. Reduction of the in vivo burst release of insulin-loaded microparticles. J. Drug Deliv. Sci. Technol., 2015, 30, 486-493.
Lengyel, M.; Kállai-Szabó, N.; Antal, V.; Laki, A.; Antal, I. Microparticles, microspheres, and microcapsules for advanced drug delivery. Sci. Pharm., 2019, 87(3), 20.
Royal pharmaceutical society of Great Britain, British medical association. BNF: British National Formulary - NICE 2019.
Trulicity 0.75 mg solution for injection in pre-filled pen - Summary of Product Characteristics (SmPC) - (emc). https://www. INETIC_PROPS [Jan 17, 2020]
Park, K.; Skidmore, S.; Hadar, J.; Garner, J.; Park, H.; Otte, A.; Soh, B.K.; Yoon, G.; Yu, D.; Yun, Y.; Lee, B.K.; Jiang, X.; Wang, Y. Injectable, long-acting PLGA formulations: analyzing PLGA and understanding microparticle formation. J. Control. Release, 2019, 304, 125-134.
[ ] [PMID: 31071374]
Wong, C.Y.; Al-Salami, H.; Dass, C.R. Microparticles, microcapsules and microspheres: a review of recent developments and prospects for oral delivery of insulin. Int. J. Pharm., 2018, 537(1-2), 223-244.
[ ] [PMID: 29288095]
Wu, Z.M.; Zhou, L.; Guo, X.D.; Jiang, W.; Ling, L.; Qian, Y.; Luo, K.Q.; Zhang, L.J. HP55-coated capsule containing PLGA/RS nanoparticles for oral delivery of insulin. Int. J. Pharm., 2012, 425(1-2), 1-8.
[ ] [PMID: 22248666]
Rekha, M.R.; Sharma, C.P. Oral delivery of therapeutic protein/peptide for diabetes--future perspectives. Int. J. Pharm., 2013, 440(1), 48-62.
[ ] [PMID: 22503954]
Cai, Y.; Wei, L.; Ma, L.; Huang, X.; Tao, A.; Liu, Z.; Yuan, W. Long-acting preparations of exenatide. Drug Des. Devel. Ther., 2013, 7, 963-970.
[PMID: 24039406]
Hamishehkar, H.; Emami, J.; Najafabadi, A.R.; Gilani, K.; Minaiyan, M.; Hassanzadeh, K.; Mahdavi, H.; Koohsoltani, M.; Nokhodchi, A. Pharmacokinetics and pharmacodynamics of controlled release insulin loaded PLGA microcapsules using dry powder inhaler in diabetic rats. Biopharm. Drug Dispos., 2010, 31(2-3), 189-201.
[ ] [PMID: 20238376]
Keles, H.; Naylor, A.; Clegg, F.; Sammon, C. Investigation of factors influencing the hydrolytic degradation of single PLGA microparticles. Polym. Degrad. Stabil., 2015, 119, 228-241.
Guarino, V.; Gentile, G.; Sorrentino, L.; Ambrosio, L. Polycaprolactone: synthesis, properties, and applications; Encycloped. Polymer Sci. Technol, 2017, pp. 1-36.
Gagliardi, M.; Michele, F.; Mazzolai, B.; Bifone, A. Chemical synthesis of a biodegradable PEGylated copolymer from ε-caprolactone and γ-valerolactone: evaluation of reaction and functional properties. J. Polym. Res., 2015, 22, 1-12.
Zhu, C.; Huang, Y.; Zhang, X.; Mei, L.; Pan, X.; Li, G.; Wu, C. Comparative studies on exenatide-loaded poly (D,L-lactic-co-glycolic acid) microparticles prepared by a novel ultra-fine particle processing system and spray drying. Colloids Surf. B Biointerfaces, 2015, 132, 103-110.
[ ] [PMID: 26037698]
Moonschi, F.H.; Hughes, C.B.; Mussman, G.M.; Fowlkes, J.L.; Richards, C.I.; Popescu, I. Advances in micro- and nanotechnologies for the GLP-1-based therapy and imaging of pancreatic beta-cells. Acta Diabetol., 2018, 55(5), 405-418.
[ ] [PMID: 29264724]
Yu, M.; Benjamin, M.M.; Srinivasan, S.; Morin, E.E.; Shishatskaya, E.I.; Schwendeman, S.P.; Schwendeman, A. Battle of GLP-1 delivery technologies. Adv. Drug Deliv. Rev., 2018, 130, 113-130.
[ ] [PMID: 30009885]
Song, R.; Murphy, M.; Li, C.; Ting, K.; Soo, C.; Zheng, Z. Current development of biodegradable polymeric materials for biomedical applications. Drug Des. Devel. Ther., 2018, 12, 3117-3145.
[ ] [PMID: 30288019]
Wang, J.; Jin, X.; An, P.; Yu, S.; Mu, Y. The Effects of Exenatide Once Weekly (EXQW) and Exenatide Twice a Day (EXBID) on beta-cell function in type 2 diabetes: a systematic review and network meta-analysis. J. Diabetes Res., 2019, 20198083417
[ ] [PMID: 31772945]
Pinho, A.R.; Fortuna, A.; Falcão, A.; Santos, A.C.; Seiça, R.; Estevens, C.; Veiga, F.; Ribeiro, A.J. Comparison of ELISA and HPLC-MS methods for the determination of exenatide in biological and biotechnology-based formulation matrices. J. Pharm. Anal., 2019, 9(3), 143-155.
[ ] [PMID: 31297291]
Ji, L.; Onishi, Y.; Ahn, C.W.; Agarwal, P.; Chou, C.W.; Haber, H.; Guerrettaz, K.; Boardman, M.K. Efficacy and safety of exenatide once-weekly vs exenatide twice-daily in Asian patients with type 2 diabetes mellitus. J. Diabetes Investig., 2013, 4(1), 53-61.
[ ] [PMID: 24843631]
Shiehzadeh, F.; Tafaghodi, M.; Dehghani, M.; Mashhoori, F.; Bazzaz, B.S.F.; Imenshahidi, M. Preparation and characterization of a dry powder inhaler composed of PLGA large porous particles encapsulating gentamicin sulfate. Adv. Pharm. Bull., 2019, 9(2), 255-261.
Ungaro, F.; d’Emmanuele di Villa Bianca, R.; Giovino, C.; Miro, A.; Sorrentino, R.; Quaglia, F.; La Rotonda, M.I. Insulin-loaded PLGA/cyclodextrin large porous particles with improved aerosolization properties: in vivo deposition and hypoglycaemic activity after delivery to rat lungs. J. Control. Release, 2009, 135(1), 25-34.
[ ] [PMID: 19154761]
Hamishehkar, H.; Emami, J.; Najafabadi, A.R.; Gilani, K.; Minaiyan, M.; Mahdavi, H.; Nokhodchi, A. Effect of carrier morphology and surface characteristics on the development of respirable PLGA microcapsules for sustained-release pulmonary delivery of insulin. Int. J. Pharm., 2010, 389(1-2), 74-85.
[ ] [PMID: 20085803]
Malathi, S.; Nandhakumar, P.; Pandiyan, V.; Webster, T.J.; Balasubramanian, S. Novel PLGA-based nanoparticles for the oral delivery of insulin. Int. J. Nanomedicine, 2015, 10, 2207-2218.
[PMID: 25848248]
França, D.; Morais, D.; Bezerra, E.; Araújo, E.; Wellen, R. Photodegradation mechanisms on Poly(E-Caprolactone) (PCL). Mater. Res., 2018, 21(5)e20170837
Barakat, N.S.; Shazly, G.A.; Almedany, A.H. Influence of polymer blends on the characterization of gliclazide--encapsulated into poly (ε-caprolactone) microparticles. Drug Dev. Ind. Pharm., 2013, 39(2), 352-362.
[ ] [PMID: 22540378]
Wischke, C.; Schneider, C.; Neffe, A.T.; Lendlein, A. Polyalkylcyanoacrylates as in situ formed diffusion barriers in multimaterial drug carriers. J. Control. Release, 2013, 169(3), 321-328.
[ ] [PMID: 23462672]
Graf, A.; Rades, T.; Hook, S.M. Oral insulin delivery using nanoparticles based on microemulsions with different structure-types: optimisation and in vivo evaluation. Eur. J. Pharm. Sci., 2009, 37(1), 53-61.
[ ] [PMID: 19167488]
Luo, Y.Y.; Xiong, X.Y.; Tian, Y.; Li, Z.L.; Gong, Y.C.; Li, Y.P. A review of biodegradable polymeric systems for oral insulin delivery. Drug Deliv., 2016, 23(6), 1882-1891.
[PMID: 26066036]
Bakshi, P.; Selvakumar, D.; Kadirvelu, K.; Kumar, N. Chitosan as an environment friendly biomaterial – a review on recent modifications and applications. Int. J. Biol. Macromol., 2020, 150, 1072-1083.
[PMID: 31739057]
Su, F.Y.; Lin, K.J.; Sonaje, K.; Wey, S.P.; Yen, T.C.; Ho, Y.C.; Panda, N.; Chuang, E.Y.; Maiti, B.; Sung, H.W. Protease inhibition and absorption enhancement by functional nanoparticles for effective oral insulin delivery. Biomaterials, 2012, 33(9), 2801-2811.
[ ] [PMID: 22243802]
Palacio, J.; Orozco, V.; López, B. Effect of the molecular weight on the physicochemical properties of poly(lactic acid) nanoparticles and on the amount of ovalbumin adsorption. J. Braz. Chem. Soc., 2011, 22, 2304-2311.
Li, J.; Sabliov, C. PLA/PLGA nanoparticles for delivery of drugs across the blood-brain barrier. Nanotechnol. Rev., 2013, 2, 241.
Khutoryanskiy, V.V. Advances in mucoadhesion and mucoadhesive polymers. Macromol. Biosci., 2011, 11(6), 748-764.
[ ] [PMID: 21188688]
Lai, S.K.; Wang, Y.Y.; Hanes, J. Mucus-penetrating nanoparticles for drug and gene delivery to mucosal tissues. Adv. Drug Deliv. Rev., 2009, 61(2), 158-171.
[ ] [PMID: 19133304]
Ensign, L.M.; Cone, R.; Hanes, J. Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers. Adv. Drug Deliv. Rev., 2012, 64(6), 557-570.
[ ] [PMID: 22212900]
Yoncheva, K.; Gómez, S.; Campanero, M.A.; Gamazo, C.; Irache, J.M. Bioadhesive properties of pegylated nanoparticles. Expert Opin. Drug Deliv., 2005, 2(2), 205-218.
[ ] [PMID: 16296748]
Palacio, J.; Agudelo, N.; Lopez, B. Pegylation of PLA nanoparticles to improve mucus-penetration and colloidal stability for oral delivery systems. Curr. Opin. Chem. Eng., 2016, 11, 14-19.
Ibrahim, M.A.; Ismail, A.; Fetouh, M.I.; Göpferich, A. Stability of insulin during the erosion of poly(lactic acid) and poly(lactic-co-glycolic acid) microspheres. J. Control. Release, 2005, 106(3), 241-252.
[ ] [PMID: 15970349]
Xiong, X.Y.; Li, Y.P.; Li, Z.L.; Zhou, C.L.; Tam, K.C.; Liu, Z.Y.; Xie, G.X. Vesicles from pluronic/poly(lactic acid) block copolymers as new carriers for oral insulin delivery. J. Control. Release, 2007, 120(1-2), 11-17.
[ ] [PMID: 17509718]
Vijayan, V.; Reddy, K.R.; Sakthivel, S.; Swetha, C. Optimization and charaterization of repaglinide biodegradable polymeric nanoparticle loaded transdermal patchs: in vitro and in vivo studies. Colloids Surf. B Biointerfaces, 2013, 111, 150-155.
[ ] [PMID: 23792547]
Barwal, I.; Sood, A.; Sharma, M.; Singh, B.; Yadav, S.C. Development of stevioside pluronic-F-68 copolymer based PLA-nanoparticles as an antidiabetic nanomedicine. Colloids Surf. B Biointerfaces, 2013, 101, 510-516.
[ ] [PMID: 23022553]
Shan, W.; Zhu, X.; Tao, W.; Cui, Y.; Liu, M.; Wu, L.; Li, L.; Zheng, Y.; Huang, Y. Enhanced oral delivery of protein drugs using zwitterion-functionalized nanoparticles to overcome both the diffusion and absorption barriers. ACS Appl. Mater. Interfaces, 2016, 8(38), 25444-25453.
[ ] [PMID: 27588330]
Mokale, V.J.; Nalk, J.B.; Verma, U.; Patil, J.S.; Yadava, S.K. Preparation and characterization of biodegradable glimepiride loaded PLA Nanoparticles by O/W solvent evaporation method using high pressure homogenizer: a factorial design approach. Scholarena J. Pharm. Pharmacol., 2014, 1, 1.
Elwerfalli, A.M.; Al-Kinani, A.; Alany, R.G.; ElShaer, A. Nano-engineering chitosan particles to sustain the release of promethazine from orodispersables. Carbohydr. Polym., 2015, 131, 447-461.
[ ] [PMID: 26256206]
Tsai, L.C.; Chen, C.H.; Lin, C.W.; Ho, Y.C.; Mi, F.L. Development of mutlifunctional nanoparticles self-assembled from trimethyl chitosan and fucoidan for enhanced oral delivery of insulin. Int. J. Biol. Macromol., 2019, 126, 141-150.
[ ] [PMID: 30586591]
Eilleia, S.; Soliman, M.; Mansour, S.; Geneidi, S. Novel technique of insulin loading into porous carriers for oral delivery. Asian. J. Pharm. Sci., 2018, 13, 297-309.
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.
[ ] [PMID: 22248882]
Momoh, A.; Mumuni, F.C.K.; Kenneth, C.; Ofokansi, A.A.; Attama, D.D.D. Insulin-loaded mucoadhesive nanoparticles based on mucin-chitosan complexes for oral delivery and diabetes treatment. Carbohydr. Polym., 2019, 11, 5506.
Avram, I.; Lupaşcu, F.G.; Confederat, L.; Constantin, S.M.; Stan, C.I.; Profire, L. Chitosan microparticles loaded with antidiabetic drugs-preparation and characterization. Farmacia, 2017, 65(3), 443-448.
Erel, G.; Kotmakçı, M.; Akbaba, H.; Sözer Karadağlı, S.; Kantarcı, A. Nanoencapsulated chitosan nanoparticles in emulsion-based oral delivery system: in vitro and in vivo evaluation of insulin loaded formulation. J. Drug Deliv. Sci. Technol., 2016, 36, 161-167.
El Leithy, E.S.; Abdel-Bar, H.M.; Ali, R.A. Folate-chitosan nanoparticles triggered insulin cellular uptake and improved in vivo hypoglycemic activity. Int. J. Pharm., 2019, 571118708
[ ] [PMID: 31593805]
Mukhopadhyay, P.; Maity, S.; Mandal, S.; Chakraborti, A.S.; Prajapati, A.K.; Kundu, P.P. Preparation, characterization and in vivo evaluation of pH sensitive, safe quercetin-succinylated chitosan-alginate core-shell-corona nanoparticle for diabetes treatment. Carbohydr. Polym., 2018, 182, 42-51.
[ ] [PMID: 29279124]
Rehm, B.H.A. Alginates: biology and applications; Springer-verlag: Berlin, Heidelberg, 2009.
George, M.; Abraham, T.E. Polyionic hydrocolloids for the intestinal delivery of protein drugs: alginate and chitosan--a review. J. Control. Release, 2006, 114(1), 1-14.
[ ] [PMID: 16828914]
Matricard, P.; Meo, C.D. coviello, T., Allhaique, F., Recent advances and perspectives on coated alginate microspheres for midifying drug delivery. Expert Opin. Drug Deliv., 2008, 5, 417-425.
[ ] [PMID: 18426383]
Kar, M.; Pratim, H.; Pillai, S.; Nagendra, S. Formulation and release characterisation of Polymer- blended alginate microspheres for an antidiabetic drug. Int. J. Innovat. Sci. Technol. 2016, pp. 16-21.
Szekalska, M.; Wróblewska, M.; Sosnowska, K.; Winnicka, K. Influence of sodium alginate on hypoglycemic activity of metformin hydrochloride in the microspheres obtained by the spray drying. Int. J. Polym. Sci., 2016, 2016, 1-12.
Chakra, B.; Karan, S.; Das, B.; Debnath, S.; Chatterjee, T. A controlled release microsphere formulation of an anti-diabetic drug and characterization of the microsphere. Int. J. Pharm. Pharm. Sci., 2018, 10, 30.
Reis, C.P.; Ribeiro, A.J.; Neufeld, R.J.; Veiga, F. Alginate microparticles as novel carrier for oral insulin delivery. Biotechnol. Bioeng., 2007, 96(5), 977-989.
[ ] [PMID: 17001630]
Szekalska, M.; Sosnowska, K.; Zakrzeska, A.; Kasacka, I.; Lewandowska, A.; Winnicka, K. The influence of chitosan cross-linking on the properties of alginate microparticles with metformin hydrochloride-in vitro and in vivo evaluation. Molecules, 2017, 22(1), 182.
[ ] [PMID: 28117747]
Patil, N.H.; Devarajan, P.V. Insulin-loaded alginic acid nanoparticles for sublingual delivery. Drug Deliv., 2016, 23(2), 429-436.
[ ] [PMID: 24901208]
Alfatama, M.; Lim, L.Y.; Wong, T.W. Alginate-C18 conjugate nanoparticles loaded in tripolyphosphate-cross-linked chitosan-oleic acid conjugate-coated calcium alginate beads as oral insulin carrier. Mol. Pharm., 2018, 15(8), 3369-3382.
[ ] [PMID: 29996652]
Al-Kassas, R.S.; Al-Gohary, O.M.; Al-Faadhel, M.M. Controlling of systemic absorption of gliclazide through incorporation into alginate beads. Int. J. Pharm., 2007, 341(1-2), 230-237.
[ ] [PMID: 17507189]
Shamekhi, F.; Tamjid, E.; Khajeh, K. Development of chitosan coated calcium-alginate nanocapsules for oral delivery of lirag-lutide to diabetic patients. Int. J. Biol. Macromol., 2018, 120(Pt A), 460-467.
[] [PMID: 30125628]
Fernández-Urrusuno, R.; Calvo, P.; Remuñán-López, C.; Vila-Jato, J.L.; Alonso, M.J. Enhancement of nasal absorption of insulin using chitosan nanoparticles. Pharm. Res., 1999, 16(10), 1576-1581.
[ ] [PMID: 10554100]
Sarmento, B.; Ribeiro, A.; Veiga, F.; Sampaio, P.; Neufeld, R.; Ferreira, D. Alginate/chitosan nanoparticles are effective for oral insulin delivery. Pharm. Res., 2007, 24(12), 2198-2206.
[ ] [PMID: 17577641]
Ma, Z.; Lim, T.M.; Lim, L.Y. Pharmacological activity of peroral chitosan-insulin nanoparticles in diabetic rats. Int. J. Pharm., 2005, 293(1-2), 271-280.
[ ] [PMID: 15778065]
Li, H.; Zhang, Z.; Bao, X.; Xu, G.; Yao, P. Fatty acid and quaternary ammonium modified chitosan nanoparticles for insulin delivery. Colloids Surf. B Biointerfaces, 2018, 170, 136-143.
[ ] [PMID: 29894834]
Aditi Bhattacharyya, D.M.; Roshnara Mishra, P.P. Kundu, Preparation of polyurethane–alginate/chitosan core shell nanoparticles for the purpose of oral insulin delivery. Eur. Polym. J., 2017, 92, 294-313.
Zhang, N.; Li, J.; Jiang, W.; Ren, C.; Li, J.; Xin, J.; Li, K. Effective protection and controlled release of insulin by cationic β-cyclodextrin polymers from alginate/chitosan nanoparticles. Int. J. Pharm., 2010, 393(1-2), 212-218.
[ ] [PMID: 20394813]
Chinnaiyan, S.K.; Deivasigamani, K.; Gadela, V.R. Combined synergetic potential of metformin loaded pectin-chitosan biohybrids nanoparticle for NIDDM. Int. J. Biol. Macromol., 2019, 125, 278-289.
[ ] [PMID: 30521906]
Tahereh Azizi Vahed, M.R.N-J. Leila Panahi, Alginate-coated ZIF-8 metal-organic framework as a green and bioactive platform for controlled drug release. J. Drug Deliv. Sci. Technol., 2019, 49, 570-576.
Amiya kumar Prusty, a. S. K. S., Development and evaluation of insulin incorporated. ISRN Nanotechnol., 2013, 2013, 6.
Qi, F.; Wu, J.; Li, H.; Ma, G. Recent research and development of PLGA/PLA microspheres/nanoparticles: a review in scientific and industrial aspects front. Chem. Sci. Eng., 2019, 13, 14-27.
Courts, A. The N-terminal amino acid residues of gelatin. Biochem. J., 1955, 59(3), 382-386.
[ ] [PMID: 14363105]
Jones, R. Gelatin manufacture and physio-chemical properties; Pharmaceut. Capsules, 2004, pp. 23-29.
Marty, J.J.; Oppenheim, R.C.; Speiser, P. Nanoparticles--a new colloidal drug delivery system. Pharm. Acta Helv., 1978, 53(1), 17-23.
[PMID: 643885]
Lai, P.; Daear, W.; Löbenberg, R.; Prenner, E.J. Overview of the preparation of organic polymeric nanoparticles for drug delivery based on gelatine, chitosan, poly(d,l-lactide-co-glycolic acid) and polyalkylcyanoacrylate. Colloids Surf. B Biointerfaces, 2014, 118, 154-163.
[ ] [PMID: 24769392]
Inoo, K.; Bando, H.; Tabata, Y. Insulin secretion of mixed insulinoma aggregates-gelatin hydrogel microspheres after subcutaneous transplantation. Regen. Ther., 2018, 8, 38-45.
[ ] [PMID: 30271864]
Inoo, K.; Bando, H.; Tabata, Y. Enhanced survival and insulin secretion of insulinoma cell aggregates by incorporating gelatin hydrogel microspheres. Regen. Ther., 2018, 8, 29-37.
[ ] [PMID: 30271863]
Wang, J.; Tabata, Y.; Morimoto, K. Aminated gelatin microspheres as a nasal delivery system for peptide drugs: evaluation of in vitro release and in vivo insulin absorption in rats. J. Control. Release, 2006, 113(1), 31-37.
[ ] [PMID: 16707188]
Zhao, Y.Z.; Li, X.; Lu, C.T.; Xu, Y.Y.; Lv, H.F.; Dai, D.D.; Zhang, L.; Sun, C.Z.; Yang, W.; Li, X.K.; Zhao, Y.P.; Fu, H.X.; Cai, L.; Lin, M.; Chen, L.J.; Zhang, M. Experiment on the feasibility of using modified gelatin nanoparticles as insulin pulmonary administration system for diabetes therapy. Acta Diabetol., 2012, 49(4), 315-325.
[ ] [PMID: 22124766]
Sonaje, K.; Lin, K.J.; Wey, S.P.; Lin, C.K.; Yeh, T.H.; Nguyen, H.N.; Hsu, C.W.; Yen, T.C.; Juang, J.H.; Sung, H.W. Biodistribution, pharmacodynamics and pharmacokinetics of insulin analogues in a rat model: oral delivery using pH-responsive nanoparticles vs. subcutaneous injection. Biomaterials, 2010, 31(26), 6849-6858.
[ ] [PMID: 20619787]
Sung, H.W.; Sonaje, K.; Liao, Z.X.; Hsu, L.W.; Chuang, E.Y. pH-responsive nanoparticles shelled with chitosan for oral delivery of insulin: from mechanism to therapeutic applications. Acc. Chem. Res., 2012, 45(4), 619-629.
[ ] [PMID: 22236133]
Kratz, F. Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J. Control. Release, 2008, 132(3), 171-183.
[ ] [PMID: 18582981]
Mahobia, S.; Bajpai, J.; Bajpai, A.K. An in-vitro investigation of swelling controlled delivery of insulin from egg albumin nanocarriers. Iran. J. Pharm. Res., 2016, 15(4), 695-711.
[PMID: 28243266]
Lopes, M.; Shrestha, N.; Correia, A.; Shahbazi, M.A.; Sarmento, B.; Hirvonen, J.; Veiga, F.; Seiça, R.; Ribeiro, A.; Santos, H.A. Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of insulin. J. Control. Release, 2016, 232, 29-41.
[ ] [PMID: 27074369]
Woitiski, C.B.; Neufeld, R.J.; Veiga, F.; Carvalho, R.A.; Figueiredo, I.V. Pharmacological effect of orally delivered insulin facilitated by multilayered stable nanoparticles. Eur. J. Pharm. Sci., 2010, 41(3-4), 556-563.
[ ] [PMID: 20800679]
Soudry-Kochavi, L.; Naraykin, N.; Di Paola, R.; Gugliandolo, E.; Peritore, A.; Cuzzocrea, S.; Ziv, E.; Nassar, T.; Benita, S. Pharmacodynamical effects of orally administered exenatide nanoparticles embedded in gastro-resistant microparticles. Eur. J. Pharm. Biopharm., 2018, 133, 214-223.
[ ] [PMID: 30342089]
Oramed reports positive results in the final cohort of its phase 2b oral insulin trial - oramed pharmaceuticals. 2020, Mar 9.
Oramed pharmaceutical's ORMD-0901 found safe and well tolerated in phase IB study. [Mar 9, 2020];
Araújo, F.; Fonte, P.; Santos, H.A.; Sarmento, B. Oral delivery of glucagon-like peptide-1 and analogs: alternatives for diabetes control? J. Diabetes Sci. Technol., 2012, 6(6), 1486-1497.
[ ] [PMID: 23294796]

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2021
Published on: 10 August, 2020
Page: [271 - 288]
Pages: 18
DOI: 10.2174/1567201817666200810111726
Price: $65

Article Metrics

PDF: 36