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Chitosan-zinc-insulin complex incorporated thermosensitive polymer for controlled delivery of basal insulin in vivo.

ABSTRACT: Thermosensitive polymeric delivery system (PLA-PEG-PLA) loaded with chitosan-zinc-insulin complex was designed for continuous in vivo insulin delivery at basal level for prolonged period after a single subcutaneous injection. Chitosan-zinc-insulin complex was optimized to restrict the diffusion of insulin from the delivery system by forming large complexes and thereby reducing the initial burst release. The in vivo absorption and bioactivity of insulin released from the delivery systems were studied in streptozotocin-induced diabetic rat model. The amount of insulin released in vivo was quantified using the Enzyme Linked Immunosorbent Assay (ELISA), and its bioactivity was determined by its ability to reduce the blood glucose levels in diabetic rats. An indirect ELISA was performed to determine the immunogenic potential of insulin released from the formulations. Furthermore, the in vitro and in vivo biocompatibility of the delivery system was studied using an MTT assay, and by studying the histology of skin samples, respectively. Chitosan-zinc-insulin complex significantly (P<0.05) reduced the initial burst release of insulin from the polymeric delivery system in comparison to zinc-insulin or insulin alone. The delivery system released insulin for ~3 months in biologically active form with corresponding reduction in blood glucose levels in diabetic rats. The insulin released from the delivery systems did not provoke any immune response. The delivery systems demonstrated excellent biocompatibility both in vitro and in vivo and were non-toxic. The results indicate that the chitosan-zinc-insulin complex incorporated in the thermosensitive polymeric delivery system can be used as an alternative to the conventional daily basal insulin therapy.

SUBMITTER: Oak M

PROVIDER: S-EPMC6172955 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Chitosan-zinc-insulin complex incorporated thermosensitive polymer for controlled delivery of basal insulin in vivo.

Oak Mayura M Singh Jagdish J

Journal of controlled release : official journal of the Controlled Release Society 20120807 2

Thermosensitive polymeric delivery system (PLA-PEG-PLA) loaded with chitosan-zinc-insulin complex was designed for continuous in vivo insulin delivery at basal level for prolonged period after a single subcutaneous injection. Chitosan-zinc-insulin complex was optimized to restrict the diffusion of insulin from the delivery system by forming large complexes and thereby reducing the initial burst release. The in vivo absorption and bioactivity of insulin released from the delivery systems were stu ...[more]

PMID: 22902516

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Project description:Purpose:Osteomyelitis, particularly chronic osteomyelitis, remains a major challenge for orthopedic surgeons. The traditional treatment for osteomyelitis, which involves antibiotics and debridement, does not provide a complete solution for infection and bone repair. Antibiotics such as vancomycin (VCM) are commonly used to treat osteomyelitis in clinical settings. VCM use is limited by a lack of effective delivery methods that provide sustained, high doses to entirely fill irregular bone tissue to treat infections. Methods:We engineered a chitosan (CS)-based thermosensitive hydrogel to produce a VCM-nanoparticle (NPs)/Gel local drug delivery system. The VCM-NPs were formed with quaternary ammonium chitosan and carboxylated chitosan nanoparticles (VCM-NPs) by positive and negative charge adsorption to enhance the encapsulation efficiency and drug loading of VCM, with the aim of simultaneously preventing infection and repairing broken bones. This hydrogel was evaluated in a rabbit osteomyelitis model. Results:The VCM-NPs had high encapsulation efficiency and drug loading, with values of 60.1±2.1% and 24.1±0.84%, respectively. When embedded in CS-Gel, the VCM-NPs maintained their particle size and morphology, and the injectability and thermosensitivity of the hydrogel, which were evaluated by injectability test and rheological measurement, were retained. The VCM-NPs/Gel exhibited sustained release of VCM over 26 days. In vitro tests revealed that the VCM-NPs/Gel promoted osteoblast proliferation and activity against Staphylococcus aureus. In vivo, VCM-NPs/Gel (with 10 mg vancomycin per rabbit) was used to treat rabbits with osteomyelitis. The VCM-NPs/Gel showed excellent anti-infection properties and accelerating bone repair under osteomyelitis conditions. Conclusion:The reported multifunctional NPs hydrogel system for local antibiotic delivery (VCM-NPs/Gel) showed bone regeneration promotion and anti-infection properties, demonstrating significant potential as a scaffold for effective treatment of osteomyelitis.

Dataset Information

Chitosan-zinc-insulin complex incorporated thermosensitive polymer for controlled delivery of basal insulin in vivo.

Publications

Chitosan-zinc-insulin complex incorporated thermosensitive polymer for controlled delivery of basal insulin in vivo.

Similar Datasets

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