No abstract

Simultaneous prolonged delivery of therapeutic gene, hydrophilic and hydrophobic anticancer drugs using biocompatible pH-sensitive LipoNiosome has been considered as a novel and promising method in order to treatment multi-drug resistant cancer.

A novel approach was developed for the preparation of stealth controlled-release liposomal doxorubicin. Various liposomal formulations were prepared by employing both thin film and pH gradient hydration techniques. The optimum formulation contained phospholipid and cholesterol in 1:0.43 molar ratios in the presence of 3% DSPE-mPEG (2000). The liposomal formulation was evaluated by determining mean size of vesicle, encapsulation efficiency, polydispersity index, zeta potentials, carrier's functionalization, and surface morphology. The vesicle size, encapsulation efficiency, polydispersity index, and zeta potentials of purposed formula were 93.61 nm, 82.8%, 0.14, and -23, respectively. Vesicles were round-shaped and smooth-surfaced entities with sharp boundaries. In addition, two colorimetric methods for cytotoxicity assay were compared and the IC (the half maximal inhibitory concentration) of both methods for encapsulated doxorubicin was determined to be 0.1 μg/ml. The results of kinetic drug release were investigated at several different temperatures and pH levels, which showed that purposed formulation was thermo and pH sensitive.

This study focuses on the development of a universal mathematical model for drug release kinetics from liposomes to allow in silico prediction of optimal conditions for fine-tuned controlled drug release. As a prelude for combined siRNA-drug delivery, nanoliposome formulations were optimized using various mole percentages of a cationic lipid (1,2-dioleoyl-3-trimethylammonium-propane, DOTAP) in the presence or absence of 3 mol% distearoyl phosphoethanolamine, polyethylene glycol (PEG-2000mDSPE). Outcome parameters were particle size, zeta potential, entrapment efficiency, in vitro drug release, and tumor cell kill efficiency. The optimized formula (containing 20% DOTAP with 3% DSPE-mPEG(2000) was found to be stable for six months, with round-shaped particles without aggregate formation, an average diameter of 71 nm, a suitable positive charge, and 89% drug encapsulation efficiency (EE). The 41% drug release during 6 h confirmed controlled release. Furthermore, the release profiles as functions of pH and temperature were investigated and the kinetics of the drug release could adequately be fitted to Korsmeyer-Peppas' model by multiple regression analysis. The statistical parameters confirmed good conformity of final models. Functionality of the novel cationic liposome formulations (± DOX) was tested on osteosarcoma (OS) cell lines. Increased OS cell toxicity (1.3-fold) was observed by the DOX-loaded vs. the free DOX. A feasibility pilot showed that siRNA could be loaded efficiently as well. In conclusion, we have established a predictive mathematical model for the fine-tuning of controlled drug release from liposomal formulations, while creating functional drug-delivery liposomes with potential for siRNA co-delivery to increase specificity and efficacy.