Multifunctional polymeric micelles for the simultaneous delivery of siRNA and chemotherapeutic agents: A promising strategy to reverse the drug resistance in the treatment of cancer
Giuseppina Salzano
Kuwait University, Kuwait
: J Pharm Drug Deliv Res
Abstract
Meloxicam is a non-steroidal anti-inflammatory drug of the oxicam class, used to relieve the symptoms of dental pain, arthritis, primary dysmenorrhea, fever and as an analgesic, especially where there is an inflammatory component. Meloxicam inhibits cyclooxygenase (COX) synthesis. This enzyme is responsible for converting arachidonic acid into prostaglandin H2. This is the first step in the synthesis of prostaglandins, which are mediators of inflammation. Meloxicam has been shown, especially at its low therapeutic dose, selectively to inhibit COX-2 over COX-1. The co-grinding technique, unlike the other solid dispersion techniques, was economically and environmentally desirable. In co-grinding approach, the use of toxic organic solvents could be easily avoided. Therefore, it was suitable for industrial manufacture on a large scale. Co-grinding of poorly water soluble drug (Meloxicam) particles with different hydrophilic polymers like PEG and / or PVP-K25 resulted in the formation of amorphous powders having enhanced drug solubility and dissolution properties , even if much smaller amount of hydrophilic polymers were used (MLX/hydrophilic polymers =1:1, w/w). According to percentage of drug dissolved, dissolution rate of MLX – PEG co-ground binary mixture prepared by ball mill or vibrational mill > MLX – PEG – PVP co-ground ternary mixture > MLX – PVP co-ground binary mixture > MLX – polymer physical mixture > MLX alone. As regards to the grinding techniques, co-ground mixtures prepared with ball mill has a relatively higher dissolution rate than those prepared with vibrational mill for all of the selected polymers at all of the employed ratios. An increase in the concentration of carrier in the co-ground blends resulted in an increase in the dissolution rate of MLX. The enhancement of dissolution of MLX from co-ground mixtures could be due to the reduction of crystalline nature of the drug in coground mixtures. Among all the prepared mixtures in this study, co-ground mixture of MLX and PEG in 1:4 ratio by ball mill showed the best results in terms of extent and rate of dissolution in water and phosphate buffer. This effect was not only due to particle size reduction, but also loss of crystalline nature of the drug during co-grinding. DSC and PXRD studies indicated that crystalline nature of drug was reduced after co-grinding with PEG and / or PVP as compared to their corresponding physical mixtures. SEM images showed that particle size of MLX was reduced after co-grinding with hydrophilic polymer PEG using ball mill.