Paclitaxel (PTX) is a potent anticancer agent whose clinical usefulness is marred by a delivery problem that is caused by its unfavorable pharmacokinetic and physical properties. Paclitaxel is currently formulated in a mixture of Cremophor EL and ethanol, which is diluted 5-20 times with normal saline or 5% dextrose prior to administration via slow infusion to avoid precipitation in plasma. Many adverse reactions to the PTX formulation have been reported because of the presence of Cremophor EL, including hypersensitivity reactions, nephrotoxicity, and neurotoxicity. Cremophor EL also causes vasodilation, labored breathing, lethargy, hypotension, and leaching of plasticizers, such as diethylhexylpthalate, from the polyvinylchloride infusion bags/sets. Significant research efforts have been conducted to develop an alternative formulation approach to increase the aqueous solubility of PTX without using Cremophor, thereby decreasing its toxicity. This article reviews the various investigated formulation approaches including pastes; liposomes; conjugates with antibodies, peptides, and fatty acids; nanospheres and microspheres; cyclodextrin complexes; emulsions; mucoadhesive gel; prodrugs; and nanoparticulate systems. The pros and cons of each approach are also discussed. Finally, this review concludes with a discussion of nanoparticulate delivery, which is the most promising PTX delivery system of the future because it incorporates the benefits of other approaches such as conjugation, complexation, and prodrugs.

The purpose of this study was to investigate the stabilizing action of polyols against various protein degradation mechanisms (eg, aggregation, deamidation, oxidation), using a model protein lysozyme. Differential scanning calorimeter (DSC) was used to measure the thermodynamic parameters, mid point transition temperature and calorimetric enthalpy, in order to evaluate conformational stability. Enzyme activity assay was used to corroborate the DSC results. Mannitol, sucrose, lactose, glycerol, and propylene glycol were used as polyols to stabilize lysozyme against aggregation, deamidation, and oxidation. Mannitol was found to stabilize lysozyme against aggregation, sucrose against deamidation both at neutral pH and at acidic pH, and lactose against oxidation. Stabilizers that provided greater conformational stability of lysozyme against various degradation mechanisms also protected specific enzyme activity to a greater extent. It was concluded that DSC and bioassay could be valuable tools for screening stabilizers in protein formulations.

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