Curcumin encapsulated pH sensitive gelatin based interpenetrating polymeric network nanogels for anti cancer drug delivery

Curcumin (CUR), a yellow bioactive compound of the Indian spice, turmeric, has antibacterial, antifungal, antioxidant, anti amoebic anti-inflammatory, anti-diabetic, antispasmodic applications as well as antiproliferative activity in vitro against many different types of cancer cells, including cancers of the colon, prostate, and breast. The poor solubility and slow dissolution rates are contributing factors because of its low bioavailability, which is approximately 60% and rapid degradation in physiological pH. Despite its various therapeutic properties, CUR lacks bioavailability due mainly to its poor solubility in water. On the other hand, the encapsulation of hydrophobic drugs into responsive nanogels (NGs) is advantageous because of its structural stability, which prevents environmental degradation and also improves their bioavailability. In this work, interpenetrating polymeric network nanogels (IPN-NGs) composed of gelatin (GL) and acrylamidoglycolic acids (AGA) were developed by emulsion polymerization. In this method, multi cross linkers were used for the fabrication of NGs. The hydrophobic CUR was encapsulated successfully into hydrophilic IPN-NGs via in situ by dissolving in an acetone–water mixture, which was then added to the reaction mixture during polymerization. FTIR, DLS, and zeta potential data showed IPN-NGs exhibited good pH sensitive properties with higher stability due to dual crosslinking as well as the inter- and intra-molecular hydrogen bonds developed between the polymer chains. XRD and DSC data showed molecular level distribution of CUR in the NG networks.  TEM results support the size of NGs and were spherical in nature. From, an Invitro release study indicates that there was no burst release of CUR. According to Peppas equation the n values were obtained for in vitro release data between 0.23 and 0.47, indicating a complete Fickian diffusion trend. Environmental degradation of the CUR was prevented because the drug molecules were well dispersed and stable in the networks. The CUR loaded NGs were highly dispersible in aqueous solutions and exhibited enhanced anti cancer activity on the colorectal cancer cells than pristine CUR. Because, the CUR loaded NGs could improve the aqueous dispersability of the drug and make it more bioavailable.