Predicting the solubility of the anti-cancer agent docetaxel in small molecule excipients using computational methods.

Purpose: To develop an in silico model that provides an accurate prediction of the relative solubility of the lipophilic anticancer agent docetaxel in various excipients.

Materials And Methods: The in silico solubility of docetaxel in the excipients was estimated by means of the solubility (delta) and Flory-Huggins interaction (chi (FH)) parameters. The delta values of docetaxel and excipients were calculated using semi-empirical methods and molecular dynamics (MD) simulations.

Long-circulating poly(ethylene glycol)-coated emulsions to target solid tumors.

The purpose of this study was to develop oil-in-water emulsions (100-120 nm in diameter) and to correlate the surface properties of the emulsions with blood residence time and accumulation into neoplastic tissues by passive targeting. We investigated the effect of phospholipid and sphingolipid emulsifiers, hydrogenated soybean phosphatidylcholine (HSPC) and egg sphingomyelin (ESM), in combination with polysorbate 80 (PS-80) and 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine (DSPE)-PEG lipids of various PEG chain lengths and structures in prolonging circulation time and enhancing accumulation into B16 melanoma or C26 colon adenocarcinoma. The relationship between amphiphile molecular packing at the air/water interface on emulsion stability upon dilution in albumin and circulation longevity in vivo was also explored for non-PEGylated emulsions.

Novel long-circulating lipid nanocapsules.

Purpose: To develop and evaluate novel long-circulating lipid nanocapsules (LN) designed for tumor delivery of lipophilic drugs.

Methods: Nanocapsules were produced by a solvent-free phase inversion process and were coated with polyethylene glycoldistearoylphosphatidylethanolamine conjugate (DSPE-PEG) during preparation or by a post-insertion step. In vivo studies were conducted in rats to assess LN pharmacokinetics and biodistribution.

In situ-forming pharmaceutical organogels based on the self-assembly of L-alanine derivatives.

Purpose: To characterize novel pharmaceutical organogels based on the self-assembly of L-alanine derivatives in hydrophobic vehicles.

Methods: The gelation properties of N-lauroyl-L-alanine (LA) and N-lauroyl-L-alanine methyl ester (LAM) were investigated in the presence of various solvents. Gel-sol and sol-gel transitions were evaluated by the inverse flow method, and gelation kinetics were determined by turbidimetry.