Effective oral delivery of insulin in animal models using vitamin B12-coated dextran nanoparticles
Abstract
The potential utility of vitamin B12 carrier system for the oral delivery of conjugated peptides/proteins and enhancement of nanoparticles (NPs) transport has been demonstrated. The present study aims to optimize the effectiveness of VB12-NPs conjugates using different levels of cross-linking, linked with different VB(12)-coatings and evaluates in animal models to investigate an efficient insulin carrier. Amino alkyl VB12 derivatives suitable for oral delivery were synthesized at 5'hydoxy ribose and e-propionamide sites via carbamate and ester/amide linkages, and were coupled to succinic acid modified dextran NPs of varied cross-linking. VB12 binding was confirmed by XPS analysis, and was quantified by HPLC (4.0 to 5.7% w/w of NPs). These polydisperse NPs conjugates showed higher size, high insulin entrapment and faster insulin release with low levels of cross-linking. These VB12-NPs conjugates (150-300 nm) showed profound (70-75% blood glucose reductions) and prolonged (54 h) anti-diabetic effects with biphasic behaviour in STZ diabetic rats. NPs with the low levels of cross-linking were found to be superior carriers, and were more effective with VB12 derivatives of carbamate linkage. The pharmacological availability relative to SC insulin was found to be 29.4%, which was superior compared to NPs conjugate of ester linked VB12 (1.5 fold) and relatively higher cross-linked particles (1.1 fold). Further, the NPs carrier demonstrated a similar oral insulin efficacy in congenital diabetic mice (60% reduction at 20 h). Significant quantities of plasma insulin were found in both animal models (231 and 197 muIU/ml). At two investigated doses, the carrier system shows dose response. Pre-dosing with a large excess of free VB12 minimized the observed activity, indicating predominance of VB12 mediated uptake. It is concluded that VB12-dextran NPs conjugate is a viable carrier for peroral insulin delivery to treat diabetics.
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In diabetic rats, vitamin B12-NPs reduce blood glucose level (~70-75%) for 54 h with biphasic behavior.
“In diabetic rats, these vitamin B12-NPs conjugate effectively and reduce the blood glucose level (~70–75%) for an extended period of time (54 h) with biphasic behavior.”
From Targeted therapy in chronic diseases using nanomaterial-based drug delivery vehicles (2019) · cites this paper as [87]
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- Authors
- Chalasani, K. B., Russell-Jones, G. J., Jain, A. K., Diwan, P. V., & Jain, S. K.
- Affiliations
- Indian Institute of Chemical Technology (IN)
- Dr. Hari Singh Gour University (IN)
- Corresponding author
- Jain, Akhlesh K.
- Jain, Sanjay K.
- Venue
- Journal of Controlled Release
- Publisher
- Elsevier BV
- Published
- 2007-09
- Volume
- 122
- Issue
- 2
- Pages
- 141-150
- ISSN
- 0168-3659 (ISSN-L)
- OpenAlex
- W2093416811
- Cited by
- 257
- References
- 52
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 4 · 2023: 16 · 2022: 20 · 2021: 20 · 2020: 26 · 2019: 10 · 2018: 12 · 2017: 15 · 2016: 17 · 2015: 11 · 2014: 22 · 2013: 19 · 2012: 20
- FWCI
- 4.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Controlled Release (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Council of Scientific and Industrial Research, India
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- oral insulin delivery, vitamin B12, dextran nanoparticles, insulin, carbamate linkage, ester linkage, insulin secretion, blood glucose reduction, streptozotocin-induced diabetes, congenital diabetes
- MeSH terms
- Administration, Oral, Animals, Blood Glucose, Chemistry, Pharmaceutical, Cross-Linking Reagents, Dextrans, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, Dose-Response Relationship, Drug, Drug Carriers, Drug Compounding, Epichlorohydrin, Female, Hypoglycemic Agents, Insulin, Particle Size, Solubility, Species Specificity, Vitamin B 12, Mice, Inbred NOD, Rats, Wistar, Mice, Rats, Nanoparticles
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