Design and evaluation of biodegradable, biosensitive in situ gelling system for pulsatile delivery of insulin

Kashyap, Naresh; Viswanad, Bhoomi; Sharma, Gaurav; Bhardwaj, V.; Ramarao, P.; Kumar, M. N. V. Ravi

doi:10.1016/j.biomaterials.2007.01.007

Cited by 107 publications

(49 citation statements)

References 21 publications

(24 reference statements)

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“…[14][15][16] Recent studies have shown that a mixture of chitosan and glycerol phosphate (GP) disodium salt is capable of forming a gel in situ. 17 The ammonium cations of the chitosan chains and the phosphate anions of the GP induce electrostatic interactions, which are the main molecular forces involved in forming a gel with the desired mechanical properties (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Chitosan Gel as an In Situ–Forming Scaffold for Rat Bone Marrow Mesenchymal Stem Cells In Vivo

Cho

Kim

Ahn

et al. 2008

Tissue Engineering Part A

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We herein formulated and characterized an in situ-forming chitosan gel consisting of chitosan and glycerol phosphate (GP) disodium salt, and examined its use as an in vivo scaffold for rat bone marrow mesenchymal stem cells (rBMSCs). First, the phase transition behaviors of chitosan solutions formulated with and without GP were characterized as a function of temperature. Chitosan solutions containing > 20 wt % GP became a gel at 37 degrees C and maintained this form for 28 days in vitro and in vivo. Next, we examined whether the chitosan gel could act as a suitable biocompatible substrate for the attachment and proliferation of rBMSCs. Immunohistochemistry clearly demonstrated that rBMSCs survived well on the scaffold created by in situ-forming chitosan gel in rats. Injection of chitosan gel alone induced macrophage accumulation in the host tissue and at the edge of the chitosan, whereas injection of chitosan gel containing rBMSCs was associated with decreased macrophage accumulation, indicating immunosuppression by the transplanted rBMSCs. Our results collectively show for the first time that chitosan gel could serve as an in situ-forming gel scaffold for entrapped rBMSCs in vivo.

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Section: Introductionmentioning

confidence: 99%

Chitosan Gel as an In Situ–Forming Scaffold for Rat Bone Marrow Mesenchymal Stem Cells In Vivo

Cho

Kim

Ahn

et al. 2008

Tissue Engineering Part A

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“…In situ forming gels: may provide a very promising mechanism for achieving well-controlled delivery of peptides and proteins. Gel formation and drug release are also affected by multiple interacting variables such as temperature, drug loading, pH, and adhesiveness to host tissues [ 38 ] . Challenges in these systems include the control of burst release and surface-to-volume ratio of the in vivo gel formation.…”

Section: Microspherementioning

confidence: 99%

Regulatory Issues and Challenges Associated with the Development of Performance Specifications for Modified Release Parenteral Products

Martinez

Khan

2011

Long Acting Injections and Implants

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Once a parenteral product has been shown to be safe and effective, specifi cations need to be developed to ensure consistent product performance across batches and throughout the shelf life of that product. This in turn necessitates an appreciation of the physiological variables and critical quality attributes that infl uence product performance. The assessment of the critical quality attributes and manufacturing processes of new drugs provides the basis for establishing these important quality standards. This chapter provides an overview of the questions and background information that regulators of human or veterinary parenteral dosage forms may consider when establishing the criteria that will ensure repeatable product quality and performance. IntroductionThe evolution of parenteral extended release platforms pushes the bounds of our understanding of host physiology, pharmaceutical technology, and the regulatory sciences. In human medicine, these ingenious formulations ensure patient compliance, minimize undesirable fl uctuations in systemic drug concentrations, and can minimize the generalized systemic side effects associated with the administration of highly

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“…Kataoka et al synthesized hydrogels composed of poly( N -isopropylacrylamide) [poly(NIPAAm)] derivatized with a defi nite fraction of a phenylboronic acid group as a glucose sensing moiety [23] . Kashyap et al immobilized a glucose oxidase enzyme, which converts glucose into gluconic acid, on physically crosslinked hydrogels made of chitosan/ β -glycerol phosphate disodium [24] . The hydrogels demonstrated insulin release in response to glucose concentration change ( Figure 6.2 ).…”

Section: In Drug Deliverymentioning

confidence: 99%

“…Similarly, pH -regulated drug release has been obtained by using pH -responsive poly(methacrylic acid -gethylene glycol) hydrogels and benzaldehyde acetal crosslinked polyacrylamide [33 -34] . As described previously, glucose -induced insulin release has been observed in PNIPAAm hydrogels derivatized with a phenylboronic acid moiety and chitosan/ β -glycerol phosphate disodium sol -gels immobilized with glucose oxidase enzyme [23,24] .…”

Section: In Drug Deliverymentioning

confidence: 99%

In the Biomedical Arena

Misra

Gil

Lowe

2008

Polymer Grafting and Crosslinking

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Design and evaluation of biodegradable, biosensitive in situ gelling system for pulsatile delivery of insulin

Cited by 107 publications

References 21 publications

Chitosan Gel as an In Situ–Forming Scaffold for Rat Bone Marrow Mesenchymal Stem Cells In Vivo

Chitosan Gel as an In Situ–Forming Scaffold for Rat Bone Marrow Mesenchymal Stem Cells In Vivo

Regulatory Issues and Challenges Associated with the Development of Performance Specifications for Modified Release Parenteral Products

In the Biomedical Arena

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