Cremophor EL (CrEL) is commonly used to solubilize paclitaxel (Ptx); a widely established anticancer agent used against many types of cancer. Using laser-based microplate nephelometry, in this work we assessed the precipitation kinetics of Ptx in CrEL-containing formulations upon dilutions with different infusion media or upon introduction into rat plasma. The precipitation profile of Ptx was assessed for a Taxol-like formulation and compared with a preparation with reduced CrEL content. These two formulations were diluted at various ratios in compatible infusion media and with or without rat plasma. The percentages of Ptx precipitated in dilution media and protein-binding in plasma were quantified using HPLC. The findings of turbidity measurements were in good agreement with HPLC. Despite the presence of albumin, it was possible to assess turbidity within infusion solutions and predict Ptx precipitation. Upon addition to plasma, no precipitation in Taxol-like formulation occurred after 2 h. In contrast, precipitation occurred immediately in CrEL-reduced formulation. It is possible that the high percentage of protein-bound Ptx in plasma (98.5-99.2%) has inhibited drug precipitation. Turbidity measurements using laser nephelometry can provide a rapid screening tool when developing intravenous formulations for poorly soluble drugs, such as Ptx and assess its stability upon dilution in animal plasma.

Chitosan has unique physicochemical and biological features that suggest it as a good candidate for the development of safe and effective drug delivery systems. Linking drug molecules with chitosan through a functional spacer enables formulation of prodrugs that have appropriate pharmacological activities at specific desired sites. The development of formulations of targeted delivery systems for the chemotherapeutic agents, especially those with unfavorable pharmacokinetic features, like paclitaxel (PTX), can potentially alleviate the systemic cytotoxicity as well as directing therapy to the specific lesions. The main aim of this literature review is to critically evaluate the use of chitosan microspheres as a drug delivery system to enhance PTX distribution and efficacy in specific targeted sites.