Cholesterol-grafted chitosan micelles as a nanocarrier system for drug-siRNA co-delivery to the lung cancer cells.

Combined delivery of a therapeutic small interfering RNA (siRNA) and a chemotherapeutic agent to cancer cells is promising as anticancer therapy, which could offer enhanced cell killing potential and low side effect. However, simultaneous delivery to tumor is challenging. In our study, cholesterol-modified low molecular weight chitosan (MW ~ 15 kDa) was employed as a self-assembled delivery system for both siRNA and a hydrophobic chemotherapeutic agent, curcumin to cancer cells. The siRNA/curcumin loaded nanoparticles (C-CCM/siRNA) were physico-chemically characterized for particle size (165 ±â€¯2.6 nm) and zeta potential (+24.8 ±â€¯2.2 mV). The ability of CCM to condense siRNA was determined by ethidium bromide exclusion and gel retardation assay using electrophoresis. The result demonstrated that the condensation of C-CCM with siRNA was optimum at minimum N/P ratio of 40. C-CCM/siRNA was stable at 4 °C for a period of >1 month. C-CCM/siRNA was taken up efficiently by human lung carcinoma cells, A549 in a time-dependent manner. The cellular internalization of C-CCM/siRNA was observed via clathrin-mediated endocytosis as determined by using specific endocytosis inhibitors. The study demonstrated the feasibility of the use of cholesterol conjugated chitosan as a co-delivery system for both siRNA and a hydrophobic drug for combination cancer therapy.

Formulation optimization, characterization, and evaluation of in vitro cytotoxic potential of curcumin loaded solid lipid nanoparticles for improved anticancer activity.

The aim of the present research was to develop a novel, biocompatible, amenable to industrial scale up and affordable solid lipid nanoparticles (SLN) preparation of curcumin and evaluate the therapeutic efficacy in vitro using cancer cells. We have incorporated cholesterol as the lipid to prepare SLN along with the Poloxamer-188 as stabilizer. High shear homogenization was used to prepare the SLN and formulation was optimized using Quality by Design The optimized Chol CUR SLN exhibited a narrow size distribution with a particle size of 166.4±3.5nm. Percentage encapsulation (%EE) was found to be 76.9±1.9%. The SLN were further characterized by DSC, FTIR, XRD and drug release. In vitro cell studies in MDA-MB-231 (Human Breast cancer) cell line revealed that the Chol CUR SLN showed superior cytotoxicity and uptake in comparison to the free curcumin. Furthermore, Chol CUR SLN induced a significantly higher apoptosis compared to free CUR treatment. These results indicated that the curcumin encapsulated in Chol SLN was able to significantly improve the cytotoxic potential and induction of apoptosis in MDA-MB-231 cells. The promising result from our study could lead a further exploration of this nanoparticle formulation to be utilized clinically for cancer treatment.