Formulation of New Drug Delivery Systems for Insulin from Natural Bioactive Biocompatible Polymers

Overview

Journal Sci Rep

Date 2025 Jan 31

PMID 39890852

Authors

Howida A Fetouh

Engy E A Aleem

Najiyah H Mohammed

Jihad M Abd-Almajeed Aldesouky

Amel M Ismail

Affiliations

Soon will be listed here.

Abstract

New insulin drug delivery systems (IDDs): insulin@chitin; insulin@chitin-grafted (g)-guar gum were prepared by using a modified sol-gel method. Insulin vials were loaded on the safe natural inert bioactive polymers (chitin and chitin-g-GG copolymer) carriers using water green solvent. Traces amount additives were below toxicity limits. Guar gum increased the numbers of the functional groups of the polymer carrier. Insulin release monitored at 37 ± 0.5 °C and buffer solutions of pH (1.2, 6.8 and 7.4) simulating physiological body fluids: stomach, intestine colon and blood stream. Insulin released from insulin@chitin only at pH 7.4. No release observed at pH 1.2, 6.8 due strong bonding to acetyl group of chitin. Insulin@chitin-GG system showed sustained targeting insulin-release at pH: 6.8 > 7.4 > 1.2. Release data obeyed pseudo second order kinetic model indicating that IDDs is heterogeneous solid surface of energetically different active sites. Each insulin molecule occupied two active sites. The slow release at pH 1.2 indicated protection against stomach juice. Release kinetic depend on physicochemical characteristics (porosity, swelling ratio as well as peptide and amino acid sequence). Both IDDs showed negative zeta potential indicating stability against aggregation. Gaur gum improved particle size distribution and insulin release.

References

Ghanbari Mehrabani M, Karimian R, Mehramouz B, Rahimi M, Kafil H . Preparation of biocompatible and biodegradable silk fibroin/chitin/silver nanoparticles 3D scaffolds as a bandage for antimicrobial wound dressing. Int J Biol Macromol. 2018; 114:961-971. DOI: 10.1016/j.ijbiomac.2018.03.128. View

Shinya S, Fukamizo T . Interaction between chitosan and its related enzymes: A review. Int J Biol Macromol. 2017; 104(Pt B):1422-1435. DOI: 10.1016/j.ijbiomac.2017.02.040. View

Zhang S, Xin P, Ou Q, Hollett G, Gu Z, Wu J . Poly(ester amide)-based hybrid hydrogels for efficient transdermal insulin delivery. J Mater Chem B. 2020; 6(42):6723-6730. DOI: 10.1039/c8tb01466c. View

Jamwal S, Ram B, Ranote S, Dharela R, Chauhan G . New glucose oxidase-immobilized stimuli-responsive dextran nanoparticles for insulin delivery. Int J Biol Macromol. 2018; 123:968-978. DOI: 10.1016/j.ijbiomac.2018.11.147. View

Tolesa L, Gupta B, Lee M . Chitin and chitosan production from shrimp shells using ammonium-based ionic liquids. Int J Biol Macromol. 2019; 130:818-826. DOI: 10.1016/j.ijbiomac.2019.03.018. View

Ye S, Jiang L, Su C, Zhu Z, Wen Y, Shao W . Development of gelatin/bacterial cellulose composite sponges as potential natural wound dressings. Int J Biol Macromol. 2019; 133:148-155. DOI: 10.1016/j.ijbiomac.2019.04.095. View

Muniyappa R, Gubbi S . COVID-19 pandemic, coronaviruses, and diabetes mellitus. Am J Physiol Endocrinol Metab. 2020; 318(5):E736-E741. PMC: 7191633. DOI: 10.1152/ajpendo.00124.2020. View

Sudhakar S, Chandran S, Selvamurugan N, Nazeer R . Biodistribution and pharmacokinetics of thiolated chitosan nanoparticles for oral delivery of insulin in vivo. Int J Biol Macromol. 2020; 150:281-288. DOI: 10.1016/j.ijbiomac.2020.02.079. View

Homayun B, Lin X, Choi H . Challenges and Recent Progress in Oral Drug Delivery Systems for Biopharmaceuticals. Pharmaceutics. 2019; 11(3). PMC: 6471246. DOI: 10.3390/pharmaceutics11030129. View

10.

Kumar D, Rub M, Asiri A . Synthesis and characterization of geminis and implications of their micellar solution on ninhydrin and metal amino acid complex. R Soc Open Sci. 2020; 7(7):200775. PMC: 7428287. DOI: 10.1098/rsos.200775. View

11.

Paixao M, Balaban R . Application of guar gum in brine clarification and oily water treatment. Int J Biol Macromol. 2017; 108:119-126. DOI: 10.1016/j.ijbiomac.2017.11.166. View

12.

Fan W, Xia D, Zhu Q, Li X, He S, Zhu C . Functional nanoparticles exploit the bile acid pathway to overcome multiple barriers of the intestinal epithelium for oral insulin delivery. Biomaterials. 2017; 151:13-23. DOI: 10.1016/j.biomaterials.2017.10.022. View

13.

Robbins D, Andersen L, Bowsher R, Chance R, Dinesen B, Frank B . Report of the American Diabetes Association's Task Force on standardization of the insulin assay. Diabetes. 1996; 45(2):242-56. DOI: 10.2337/diab.45.2.242. View

14.

Fetouh H, Ismail A, Hamid H, Bashier M . Synthesis of promising nanocomposites from an antitumer and biologically active heterocyclic compound uploaded by clay and chitosan polymers. Int J Biol Macromol. 2019; 137:1211-1220. DOI: 10.1016/j.ijbiomac.2019.06.187. View

15.

Alfatama M, Lim L, Wong T . 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. DOI: 10.1021/acs.molpharmaceut.8b00391. View

16.

Bak J, Yoo B . Intrinsic viscosity of binary gum mixtures with xanthan gum and guar gum: Effect of NaCl, sucrose, and pH. Int J Biol Macromol. 2018; 111:77-81. DOI: 10.1016/j.ijbiomac.2017.12.144. View

17.

Wong C, Al-Salami H, Dass C . Microparticles, microcapsules and microspheres: A review of recent developments and prospects for oral delivery of insulin. Int J Pharm. 2017; 537(1-2):223-244. DOI: 10.1016/j.ijpharm.2017.12.036. View

18.

Patriota Y, Arruda I, de Jesus Oliveira A, Oliveira T, Vasconcelos Silva E, Chaves L . Synthesis of Eudragit® L100-coated chitosan-based nanoparticles for oral enoxaparin delivery. Int J Biol Macromol. 2021; 193(Pt A):450-456. DOI: 10.1016/j.ijbiomac.2021.10.111. View

19.

Tapdigov S . The bonding nature of the chemical interaction between trypsin and chitosan based carriers in immobilization process depend on entrapped method: A review. Int J Biol Macromol. 2021; 183:1676-1696. DOI: 10.1016/j.ijbiomac.2021.05.059. View

20.

Mallakpour S, Hatami M . Fabrication and characterization of pH-sensitive bio-nanocomposite beads havening folic acid intercalated LDH and chitosan: Drug release and mechanism evaluation. Int J Biol Macromol. 2018; 122:157-167. DOI: 10.1016/j.ijbiomac.2018.10.166. View