The objective of this present study was to develop a Novel-pH sensitive interpenetrating polymeric network micro gels based on Chitosan-acrylamide-grafted-poly- ethylene glycol followed by hydrolysis that are cross-linked with glutaradehyde. The resulting matrix is used in the controlled release of Doxorubicin an anti cancer drug. Further, prepared hydro gels were evaluated for swelling index, drug content, in-vitro release results performed in both acidic and basic media. Chitosan beads are characterized by FTIR, X-ray diffraction, SEM, and DSC, The IPN matrix these studies were able to extend the release rate from conventional dosage release time.
Key words: Chitosan, poly (ethylene glycol), hydro gels cross-linking, Controlled release Doxorubicin,
These days biocompatible and biodegradable hydro gels find a wide application in the field of medicine,Pharmaceuticals,tissues engineering, This has promoted scientists and technologists to give more attention to develop effective, useful and biodegradable hydro gels from a sustainable resource1-2Hydrogel may be chemically stable and degrade and eventually disintegrates and dissolve3 to avoid this avoid this a controlled cross linking is introduced within the hydrogels,stimuli responsive hydro gels which swell and in contract in responsive hydro gels with swells and contract in response to external pH have been explored4 Many structural factor such as concentration pKa of the ionizable group, degree of ionization cross linking densiy,hydrophillicity,influence the degree of swelling of ionic polymers5 in addition properties of the swelling medium such as pH ,ionic strength, affect the swelling characteristics 6
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A number of methods have been used for the cross linking of chitosan such as chemical cross linking with glutarldehyde10-11 This seems to be good approach to improve wet strength of hydro gels .A number of methods have been used for preparing IPN polymeric network of chitosan has been reported by12 We further promote their work and observe the external stimuli on swelling behavior of these hydro gel we used PEG for synthesizing IPN polymeric network and also we done antimicrobial activities against gram positive and gram negative bacteria The present study report novel pH sensitive IPN polymeric net work for sustain release of Cefadroxil in different acidic and basic medium, Drug loaded hydro gel were charactd by FTIR,SEM DSC.
To our best of our knowledge no work has done so for by using this polymer for synthesizing IPN network, The present work deals with in-vitro release studies on IPN hydro gel formulation loaded with different amount of drug, The spectroscopic characteristic (FTIR) of prepared IPN hygrogel, effect of extent of cross linking and effect of temperature pH,ionic strength of swelling medium on swelling behavior of IPN were observed. The prepared IPN matrix exhibit better swelling behavior than the other reported chitosan hydro gels experimental
Doxorubicin USP Grade ,Chitosan poly(D-glucosamine)purchased from sigma Aldrich product of china,acrylamid were purchased from Qualigens,Mumbai India,poly ethylene glycol 4000(PEG),Hydrochloric acid, Glutardehyde,Glacial acetic acid, sodium hydroxide and other chemical purchased from Sd. fine chemicals and were of AR grade
Preparation of Poly ethylene glycol grafted acryl amide:
Poly ethylene glycol grafted acryl amide prepared as per reported method12, accordingly PEG was dissolved in water on heating at 60-65 oC and treated with acryl amide under nitrogen gas to this solution potassium per sulfate was introduced in a small quantity under constant stirring at a temperature 65 co for 5 h.The obtained product was precipitated in methanol and then with water-methanol (1:1 v/v).The final product was filtered and kept in a vacuum for drying at 60 oC The resultant product to make acidic 1 wt% solution of polymer blend was heated in a hot plate at 60 oC 25 ml of equimolar concentration of sodium hydroxide was added and then mixture was stirred with magnetic stirrer at 60 oC for 5 hr to complete the hydrolysis of prepared polymer blend, then 2N hydrochloric acid was added with a solution of methanol the obtained products were precipitated in methanol and washed with a solution of methanol, filter and vacuum dried at 60 oC and stored in a an airtight desiccators for further use.
Preparation of drug loaded polymer blend:
To a 1% solution of chitosan in 2% aqueous acetic acid prepared by gentle heating and stirred with a magnetic stirrer on a hot plate, a required amount of drug was added until a complete desperation of the drug in the polymer solution was obtained a portion of drug loaded polymer solution was added drop wise in to solution of ethanol solution. The required amount of glutardehyde12added, the obtained IPN network formed were removed from methanol and were repeatedly washed with distilled water to remove any unreacted materials in order to know the drug release characteristic different formulation with varying drug concentration and chitosan with polymeric blend concentration were prepared and studied.
Characterization of drug loaded polymer blend;
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The synthesized polymeric blend were evaluated for their physical properties like water content, surface pH and SEM The formation of grafted blend during the reaction was confirmed by FTIR spectral analysis
Fourier transforms Infrared Spectroscopy: IR Spectra of was carried out using KBr disc technique (Make-JASCO-4100, Japan) to identify the chemical structure of the prepared network.
Differential Scanning Calorimetry: Furthermore to find out the nature of drug in the polymeric network Differential Scanning Calorimetry (DSC) (Model DSC Q 1000 V9.4 Build 287) study was carried out at a scanning rate of 10 °C/min.
Scanning Electron Microscope (SEM) Study;
The morphology and surface topography of the prepared network was examined by SEM using model (FEI Quanta FEG 200 - High Resolution Scanning Electron Microscope).
X-ray diffraction studies (XRD): XRD Studies help to find the crystallinity of drug in the cross-linked network was performed (Brand: Bucker Germany, CuKÎ¬ radiation, Nickel filter). The XRD patterns o Doxorubicin loaded Chitosan -PEG Hydro gel blend, Placebo Doxorubicin loaded Chitosan -PEG Hydro gel blend, and XRD pattern of pure drug are compared
Results and discussion:
Characterization of drug loaded polymer blend;
This study was carried out to confirm the grafting of acryl amide as well as hydro gel PEG-grafted-Copolymer (Hydrolyzed) are presented in Figure 1. A broad band appearing at 3435.09 cm-1 corresponds to associated -OH stretching vibrations of the hydroxyl group of grafted copolymer. A new peak appeared at 3251.24 cm-1 and the related peak at 1630.35/cm corresponds to-NH bending vibrations of the primary amides of acryl amide. A relatively high intense peak at 292.51 cm-1 (Figure 1), which is characteristic to aliphatic-CH stretching vibrations in the grafted copolymer, confirms the completion of reaction. In the spectra of hydrolyzed PEG-grafted copolymer, the shoulder peak disappeared but two new peaks appeared around 1500 cm-1 and 1450 cm-1 which are due to antisymmetric vibrations of -COOH groups.
Figure 2 chitosan hydrolyzed complex observed around 1575-1590cm-1 due to NH3
The hydrophilic nature of polyacrylamide modified poly ethylene glycol was used to synthesis the micro gels blended with chitosan, this could be used for the carrier for Doxorubicin release