Enhancing the Kinetic Stability of Polymeric Nanomicelles (PLGA) Using Nano-Montmorillonite for Effective Targeting of Cancer Tumors

Abstract

The toxic profile of chemical cross-linkers used in enhancing the stability of self-assembled nanomicelles made of amphiphilic polymeric materials hinders their use in clinical applications. This study was aimed to use the layered structure of Na-montmorillonite (MMT) as a stabilizer for nanomicelles made of poly(D,L-lactide-co-glycolide) (PLGA) amphiphilic polymer. The size of Na-MMT was reduced below 40 nm (nano-MMT) by processing in an attritor prior to its incorporation with PLGA. Hybrid PLGA nano-MMT (PM) nanoparticles (NPs) were prepared using dialysis nanoprecipitation. The size distribution was measured using dynamic light scattering (DLS). Loading 1250 mu g of the model drug molecule curcumin to PM (PMC) resulted in obtaining 88 nm-sized particles, suitable for passive targeting of cancer tumors. The structure of nano-MMT and its position in PMC were investigated using FT-IR, differential scanning chalorimetry (DSC), XRF, XRD, ESEM, and EDAX assays, all of which showed the exfoliated structure of nano-MMT incorporated with both hydrophilic and hydrophobic blocks of PLGA. Curcumin was mutually loaded to PLGA and nano-MMT. This firm incorporation caused a serious extension in the release of curcumin from PMC compared to PLGA (PC). Fitting the release profile to different mathematical models showed the remarkable role of nano-MMT in surface modification of PLGA NPs. The ex vivo dynamic model showed the enhanced stability of PMC in simulated blood flow, while cytotoxicity assays showed that nano-MMT does not aggravate the good toxic profile of PLGA but improves the anticancer effect of payload. Nano-MMT could be used as an effective nontoxic stabilizer agent for self-assembled NPs.