Cited by 257Advanced Drug Delivery SystemsNanoparticle-Based Drug DeliveryDrug Solubulity and Delivery Systems

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Effective oral delivery of insulin in animal models using vitamin B12-coated dextran nanoparticles

Chalasani, Kishore B., Russell-Jones, Gregory J., Jain, Akhlesh K., Diwan, Prakash V., Jain, Sanjay K.·2007·Journal of Controlled Release

DOI 10.1016/j.jconrel.2007.05.019

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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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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.
ORCID: Jain, Akhlesh K.
Diwan, Prakash V.
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)
DOI: 10.1016/j.jconrel.2007.05.019
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Effective oral delivery of insulin in animal models using vitamin B12-coated dextran nanoparticles

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