Mucoadhesive Microspheres of Chitosan and Polyvinyl Alcohol as A Carrier for Intranasal Delivery of Insulin: In Vitro and In Vivo Studies

Abstract

The aim of this study was to investigate the capabilities of chitosan microspheres as drug carrier system in co-formulation with polyvinyl alcohol (PVA), to improve the systemic absorption of intranasal insulin delivery.Insulin loaded microspheres was developed from varying ratio of chitosan solutions along with polyvinyl alcohol (PVA) as additive polymer using spray drying method. Different formulations were developed and morphological studies of the optimized formulas showed that the size range of spherical shaped particulate matters existed from 200 nm to 2 μm. It was clearly observed that physicochemical properties of the microspheres were extensively affected by changing the concentration ratio of the two polymeric materials. In vitro studies of insulin release pattern was performed in various time intervals up to 24 h. It was evident that microspheres made up of chitosan showed initial burst release but slower release as the experiment continued. Microspheres made up of combination of the aforementioned two polymers had instant, sharp and burst drug release. Surprisingly there was no absorption after intranasal delivery of chitosan-PVA microspheres in groups of rats comparing to formulated chitosan microspheres having profound absorption due to their smaller particle size, slower drug release rate and better mucoadhesive properties. Therefore, significant reduction in the plasma blood glucose level for chitosan based optimized formulation was seen right after 4.5 hours compared with control group. The aim of the present study was to fabricate an appropriate application of polymeric microspheres for intranasal delivery of insulin using a novel optimized formulation based on industrial level spray drying technique and to realize the possible barriers in scale up process of its large scale production, considering the effectiveness of polyvinyl alcohol (PVA) and chitosan to increase mucoadhesivness, gelling ability and ultimately effective release behavior pattern of insulin. According to this study, the combination of the polymers used and the mean particle size of formulated microspheres were found to be key factors in insulin drug release resulting for further enhancement of insulin absorption via intranasal route of delivery. Furthermore, avoidance of hepatic first pass metabolism makes it a preferred route for the delivery of small drug molecules but not basically the macromolecules as the permeability and degradability are rate-limiting steps in their systemic absorptions. KeywordsFeasibility of intranasal route for delivery of peptides and proteins has already been evaluated as mentioned before, due to the perceived less demanding barriers to peptides and proteins transport across the nasal epithelium as compared to the oral mucosa and nasal cavity comprising lower enzymatic content, higher leakiness of the membrane and high vascularity and no hepatic first pass metabolism But still there are few nasal peptide based products which have appeared on the market e.g. calcitonin (Miacalcin These prod...

Synthesis and Study of Modified Polyvinyl Alcohol Containing Amino acid moieties as Anticancer Agent

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Polyvinyl Alcohol-Chitosan Scaffold for Tissue Engineering and Regenerative Medicine Application: A Review

“…This suggests that slow release was achieved via the PVA-CS network. In 2017, a similar study was conducted to evaluate the potential of PVA-CS microspheres as a vehicle for insulin drug delivery via intranasal administration [ 84 ]. The authors developed different formulations, and morphological analysis of the optimized formulas showed that the size range was between 200 nm to 2 µm.…”

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