ABSTRACT
Paclitaxel, a naturally occurring diterpenoid originally extracted from the Pacific
Yew tree in the early 1960s, has been considered by the National Cancer Institute
(NCI) as the most significant advance in drug discovery for chemotherapy
and has become commercially most successful antineoplastic agent. The drug
has been known to exhibit a significant activity against a wide spectrum of
cancers, including breast cancer, ovarian cancer, colon cancer, bladder cancer,
lung cancer, head and neck carcinomas, and acute leukemia [1-4]. The main
limitation for its clinical application is its low solubility in water and most of the
pharmaceutical solvents [5]. The dosage form in its clinical application is Taxol R©, which is formulated in an adjuvant called Cremophor EL (CrEL) and dehydrated
alcohol at a 50:50 (v/v) ratio, which is diluted 5-20-fold in normal saline or
dextrose solution (5%). This adjuvant has been found associated with severe
side effects including hypersensitivity reactions, nephrotoxicity, neurotoxicity
and cardiotoxicity [6-9]. Alternative paclitaxel formulation strategies have been
suggested to eliminate the CrEL-based vehicle and to improve the therapeutic
efficacy of the drug, which include parenteral emulsions [10, 11], liposomes
[12, 13], micelles [14], nanoparticles (NPs) [15-17] and microspheres [18, 19].
Among them, NPs of biodegradable polymers could provide an ideal solution for
the alternative formulation devoid of CrEL, which may also provide a sustained,
controlled and targeted delivery of the drug and with further development,
promote oral chemotherapy [20, 21].
