Controlled Delivery of Basal Level of insulin From Chitosan–Zinc–Insulin-Complex-Loaded Thermosensitive Copolymer

Oak, Mayura; Singh, Jagdish

doi:10.1002/jps.22823

Cited by 19 publications

(21 citation statements)

References 39 publications

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“…The optimized chitosan-zinc-insulin complex loaded thermosensitive polymeric delivery systems (PLA-PEG-PLA chain length: 1500-1500-1500, molecular weight 4500 Da) were formulated as described previously [27]. The formulations were injectable through 25 G needle, and formed gel depot quickly after incubation at body temperature.…”

Section: Resultsmentioning

confidence: 99%

“…In our previously published work [27], we developed a controlled release delivery system to deliver insulin at basal level by incorporating chitosan-zinc-insulin complex into PLA-PEG-PLA (4500 Da) thermosensitive triblock copolymer. A combination approach was employed by utilizing the characteristic properties of insulin, such as self-assembly into hexamers in presence of zinc and their ability to interact with chitosan electrostatically to form chitosan-zinc-insulin complexes.…”

Section: Discussionmentioning

confidence: 99%

“…Our in vitro release studies indicated that the increased size of chitosan-zinc-insulin complex helped to reduce complex diffusion from the thermosensitive polymer gel matrix, and prolonged the insulin release in vitro. This slow diffusion of insulin resulted in reduced initial burst release, and further the complex helped to stabilize insulin during release and storage, while providing controlled release over extended duration in vitro [27]. Various analytical techniques such as circular dichroism (CD), differential scanning Calorimetry (DSC), polyacrylamide gel electrophoresis (PAGE)/SDS-PAGE, high-performance liquid chromatography (HPLC), and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) confirmed the conformational and chemical stability of insulin released from the delivery systems.…”

Section: Discussionmentioning

confidence: 99%

“…The details about the synthesis and characterization procedures are discussed earlier [14]. Chitosan-zinc-insulin complexes were designed, characterized, optimized, and incorporated into the triblock copolymer based delivery systems as described in our earlier publication [27]. Briefly, the delivery system was prepared by dissolving the triblock copolymer (30% w/w) in water at 4°C under continuous stirring.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous work, we have demonstrated the ability of chitosan-zinc-insulin complex incorporated in thermosensitive copolymer poly(D,L-lactide)-poly(ethylene glycol)-poly(D,L-lactide) (PLA-PEG-PLA, 4500 Da) based delivery system to control the release of insulin for prolonged period while maintaining its structural integrity in vitro [27]. It was observed that the complex formation played an important role in reducing the initial burst release of insulin from the polymer gel matrix, due to increased size and slow dissociation from chitosan-zinc-insulin complex, and also helped to stabilize insulin during release and storage.…”

Section: Introductionmentioning

confidence: 99%

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

Oak

Singh

2012

Journal of Controlled Release

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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 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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Oak

Singh

2012

Journal of Controlled Release

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Controlled‐Release Systems for Biologics

Oak¹,

Mandke²,

Layek³

et al. 2013

Pharmaceutical Sciences Encyclopedia

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It is evident by the progress in new drug delivery technologies that much attention has been devoted toward the way in which biologics are delivered. As shown in this chapter, present efforts in the field of delivery of biologics have accelerated and widened the possibility of their use with therapeutic agents for treatment of various chronic disorders. From the times when achieving a zero‐order release profile was just an imaginary concept and controlled release technology was known only to a few scientists, it has now been established widely and has gained significant applications in variety of fields ranging from gene therapy to tissue engineering.

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In Vitro and In Vivo Evaluation of a Once-weekly Formulation of an Antidiabetic Peptide Drug Exenatide in an Injectable Thermogel

Liu

et al. 2013

Journal of Pharmaceutical Sciences

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Controlled Delivery of Basal Level of insulin From Chitosan–Zinc–Insulin-Complex-Loaded Thermosensitive Copolymer

Cited by 19 publications

References 39 publications

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

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

Controlled‐Release Systems for Biologics

In Vitro and In Vivo Evaluation of a Once-weekly Formulation of an Antidiabetic Peptide Drug Exenatide in an Injectable Thermogel

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