HYBRID POLYVINYL ALCOHOL/ LINSEED DUAL CROSSLINKED NANOCOMPOSITE HYDROGEL LOADED WITH DOXYCYCLINE FOR THE PRODUCTION OF ACNE PATCHES

Abstract

A hydrogel nanocomposite based acne treatment patch loaded with doxycycline and a method of developing thereof is described herein. The present invention relates to the preparation of biocompatible hydrogel matrix comprising polyvinyl alcohol, linseed mucilage extract, nano zinc-oxide crosslinked dually via covalent linkages and free radical polymerization by electronic beam exposure. The pore size of the hydrogel acne patch ranges between 0.1-0.5 μm. The doxycycline loaded acne patches were able to inhibit the growth of S. aureus in an in-vitro bacterial growth inhibition assay.

Claims

1. A hydrogel formulation comprising an equal-volume of 10% (w/v) Polyvinyl alcohol and 2% (w/v) Linseed mucilage extract mixture.

2. The formulation in claim 1 wherein 0.5% (w/v) ZnO nanoparticles were incorporated into it.

3. A method of dually crosslinking the formulation claimed in claim 2 by 2% (w/v) citric acid and 30 KGY electron beam exposure to obtained hydrogel/hydrocolloid sheets.

4. The formulation claimed in claim 3, wherein the formed hydrogel sheet which were loaded with Doxycycline after being cut into smaller acne patches.

5. The formulation claimed in claim 4, wherein, it manifested a bactericidal potential against Staphylococcus aureus in an in vitro bacterial growth inhibition assay.

6. The formulation claimed in claim 3, wherein it is the first doxycycline containing hydrogel based formulation for topical application of acne treatment.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIG. 1 represents a photograph of the synthesized hydrogel sheet.

[0012] FIG. 2 represents a photograph of PVA/LS/ZnO hydrogel Patches of 1 inch diameter.

[0013] FIG. 3 shows a photograph representing dried vs swollen PVA/LS/ZnO hydrogel disk.

[0014] FIG. 4 is the SEM micrographs of (a) PVA/LS hydrogel (b) PVA/LS/ZnO hydrogel.

[0015] FIG. 5 shows the swelling behavior of PVA/LS and PVA/LS/ZnO hydrogel.

[0016] FIG. 6 is a comparison of the IR spectra of PVA/LS, PVA/LS/Dox and Doxycycline.

[0017] FIG. 7 is a comparison of the IR spectra of PVA/LS/ZnO, PVA/LS/ZnO/Dox and Doxycycline.

[0018] FIG. 8 shows the In vitro bacterial growth inhibition observed after 24 hrs for (a) PVA/LS/Dox (b) PVA/LS/ZnO/Dox

DETAILED DESCRIPTION OF THE INVENTION

[0019] The invention described herein involves the synthesis of PVA/Linseed mucilage extract nanocomposite hydrogels and their subsequent development into doxycycline loaded acne patches. The embodiment disclosed provides several benefits over the conventional acne patches including biocompatibility, ECM like wound healing potential, cooling effect, anti-microbial potential and release of drug at the target site. The formulation comprising PVA and Linseed is biocompatible and cheap, is impregnated with ZnO, dually crosslinked and subsequently loaded with doxycycline to develop into acne patches.

[0020] Synthesis of hydrogels: A 10% (w/v) Polyvinyl alcohol solution was made by dissolving the required amount of PVA in distilled water at 80° C. A homogenizer was employed to ensure thorough mixing of solution.

[0021] A 2% (w/v) linseed solution was prepared by suspending the required weight of dry linseeds in distilled water. The resulting mixture was allowed to stir at 60° C. for two hours following which the mucilage extract was strained using a strainer.

[0022] Equal volumes of 10% polyvinyl alcohol and 2% Linseed mucilage extract were mixed together and 2% (w/v) citric acid was added to it. The resulting mixture was allowed to stir for 30 minutes to yield PVA/LS based formulations

[0023] For the preparation of ZnO based formulation, 0.5% (w/v) of ZnO was added to the above mixture and the mixture was homogenized thoroughly to yield PVA/LS/ZnO based formulation.

[0024] The above formulations (were poured into polystyrene trays and exposed to 30 KGY electron beam intensity at a conveyer belt speed of 3 m/min following which they assumed a sheet like morphology; individual sheets being 3 mm in thickness as shown in FIG. 1.

[0025] Fabrication of acne patches: The freshly prepared sheet hydrogels were cut into circular patches of 1 inch diameter (as shown in FIG. 2) and allowed to dry in a vacuum oven at 50° C. before they were immersed in 3 uM doxycycline solution for drug loading. The dry and freshly prepared hydrogels sheet are shown in FIG. 3.

[0026] The PVA/LS and PVA/LS/ZnO hydrogel sheets after freeze drying were analyzed for their surface morphology by scanning electron microscopy (HVSEM) (Model; JSM-5300, Japan). FIG. 4 (a and b) shows the surface of morphology of the hydrogel sheets. The PVA/LS hydrogel sheet manifests a porous honey comb like microstructure with random closed to open cells and pore size lying in the range of 100-400 nm (0.1-0.4 μm).

[0027] SEM analysis of the PVA/LS/ZnO as shown in FIG. 4(b) revealed a transition to nanocrystalline morphology with aggregates of ZnO nanostructures adorning the hydrogel sheet surface.

[0028] Swelling behavior is an intrinsic property of hydrogels, where the hydrogels expand due to solvent penetration into the voids between the polymeric chain networks. For swelling experiments, fresh hydrogel sheets were cut into 3 cm×3 cm squares and were kept in oven to dry until constant weight. The dried squares were immersed in distilled water and their weight was periodically measured after wiping the excess water using tissue paper (FIG. 3). The timed water absorption percentages of hydrogels are presented in FIG. 5. Both PVA/LS and PVA/LS/ZnO hydrogels manifested a fast swelling behavior, swelling rather quickly in the first 10 hours, following which they attained an equilibrium swelling after a passage of 45 hours. The integrity of the sheet/disk remained unaffected in the swelling process and even after a week of immersion in distilled water. The percent swelling of PVA/LS/ZnO was evidently less than PVA/LS hydrogels since the incorporated ZnO particles occupied quite many of the water binding sites within the hydrogel network.

[0029] For drug loading and in vitro bacterial growth inhibition assay individual dried disks of PVA/LS and PVA/LS/ZnO hydrogel were subsequently immersed in a 0.3 μM doxycycline solution for 48 hours. The individual disks loaded approximately 45±0.5 μg of doxycycline. IR spectroscopy was carried out to verify the successful loading of doxycycline within the disks. As shown in FIG. 6 and FIG. 7, the appearance of specific peaks in the IR spectrum confirmed the successful loading of the drug in the PVA/LS and PVA/LS/ZnO hydrogel disk. In both spectra the peak appearing in the region of 3400 cm.sup.−1 to 3550 cm.sup.−1 corresponds to —OH of the hydrogel network. The peaks at 2932 cm.sup.−1, 2940 cm.sup.−1, and 1450 cm.sup.−1 are due to the —CH vibration and stretching. The aryl —C═O stretch at 1635 cm.sup.−1, aromatic —C═C ring stretch bands at 1520 cm.sup.−1 and peaks at 1238 cm.sup.−1, 1047 cm.sup.−1 arising from stretching of C—O in phenols and —C—O—C stretch and bending in ketones are all characteristic peaks arising from the tetracycline structure of doxycycline. In FIG. 7, the peak at 544 cm .sup.−1 corresponds to ZnO.

[0030] In the in vitro bacterial growth inhibition assay against S. aureus the PVA/LS/Dox and PVA/LS/ZnO/Dox hydrogel disks respectively manifested a zone of inhibition (ZOI) equal to 2.5±0.1 cm and 3.1±0.1 cm after 24 hours with respect to the control as shown in FIG. 8.