Folic acid conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel for site specific delivery of hydrophobic drugs to cancer cells.

Gopalakrishnapillai Sankaramangalam Kumar,Ashwanikumar Narayanan,Devika Nandan Chithralekha,Ruby John Anto,Arun Kumar Theralikattu Thulasidasan,Jisha Jayadevan Pillai

doi:10.1186/1477-3155-12-25

Gopalakrishnapillai Sankaramangalam Kumar, Ashwanikumar Narayanan + Show 4 more

Open Access

https://doi.org/10.1186/1477-3155-12-25

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Abstract

BackgroundThe hydrogel based system is found to be rarely reported for the delivery of hydrophobic drug due to the incompatibility of hydrophilicity of the polymer network and the hydrophobicity of drug. This problem can be solved by preparing semi-interpenetrating network of cross-linked polymer for tuning the hydrophilicity so as to entrap the hydrophobic drugs. The current study is to develop a folic acid conjugated cross-linked pH sensitive, biocompatible polymeric hydrogel to achieve a site specific drug delivery. For that, we have synthesized a folic acid conjugated PEG cross-linked acrylic polymer (FA-CLAP) hydrogel and investigated its loading and release of curcumin. The formed polymer hydrogel was then conjugated with folic acid for the site specific delivery of curcumin to cancer cells and then further characterized and conducted the cell uptake and cytotoxicity studies on human cervical cancer cell lines (HeLa).ResultsIn this study, we synthesized folic acid conjugated cross-linked acrylic hydrogel for the delivery of hydrophobic drugs to the cancer site. Poly (ethyleneglycol) (PEG) diacrylate cross-linked acrylic polymer (PAA) was prepared via inverse emulsion polymerization technique and later conjugated it with folic acid (FA-CLAP). Hydrophobic drug curcumin is entrapped into it and investigated the entrapment efficiency. Characterization of synthesized hydogel was done by using Fourier Transform-Infrared spectroscopy (FT-IR), Transmission Electron Microscopy (TEM), Differential Scanning Calorimetry (DSC). Polymerization and folate conjugation was confirmed by FT-IR spectroscopy. The release kinetics of drug from the entrapped form was studied which showed initial burst release followed by sustained release due to swelling and increased cross-linking. In vitro cytotoxicity and cell uptake studies were conducted in human cervical cancer (HeLa) cell lines.ConclusionsResults showed that curcumin entrapped folate conjugated cross-linked acrylic polymer (FA-CLAP) hydrogel showed higher cellular uptake than the non folate conjugated form. So this can be suggested as a better delivery system for site specific release of hydrophobic cancer drugs.

Highlights

The hydrogel based system is found to be rarely reported for the delivery of hydrophobic drug due to the incompatibility of hydrophilicity of the polymer network and the hydrophobicity of drug
We prepared acrylic polymer cross-linked with polyethylene glycol diacrylate by inverse micro emulsion polymerization method which is cross-linked with folic acid through ethylenediamine for targeted delivery of curcumin to cancer cells
Folic acid is conjugated with the hydrogel that helps in the targeted delivery of the drug encapsulated hydrogel towards the cancer cells since many cancer cells are expressing folic acid on its surface and pH sensitivity helps in the swelling of the hydrogel in the required site with the sustained release of drug on that particular site

Summary

Introduction

The hydrogel based system is found to be rarely reported for the delivery of hydrophobic drug due to the incompatibility of hydrophilicity of the polymer network and the hydrophobicity of drug. The current study is to develop a folic acid conjugated cross-linked pH sensitive, biocompatible polymeric hydrogel to achieve a site specific drug delivery. Hydrogels are polymeric networks having three-dimensional configuration capable of imbibing high amounts of water or biological fluids. Their water absorbing property is mainly attributed to the presence of hydrophilic groups such as – OH, −CONH–, −CONH2–, and –SO3H in the polymers. The porosity of hydrogel can be tuned to the required size of the drug by the addition of cross linker to it It help in the controlled release of drug [9,10]. Even though natural polymers have good bioactive properties [11] they are found to have low mechanical strength so we make use of synthetic polymers because of their good mechanical strength and well-defined structure which can be modified to improve the biocompatibility and biodegradability [12,13]

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