Paclitaxel, liposomal encapsulation

Also, paclitaxel is the most widely used anticancer agent for non-small cell lung cancer [420], Liposomal encapsulated paclitaxel faces the problem of formulation due to the drug s high hydrophobicity. However, a phase I trial with liposomal paclitaxel reported dose-limiting toxicity at the dose of 150 mg/m2/week. Besides, the whole blood clearance of paclitaxel was similar for liposomal and free paclitaxel. 

Preparations of liposomes via SCF processing are designated as critical fluid liposomes (CFLs). CFLs have successfully encapsulated hydrophobic drugs such as taxoids, camptothecins, doxorubicin, vincristine, and cisplatin. In addition, stable paclitaxel liposomes with a size of 150-250 nm were obtained. Aphios Co. s patent (US Patent 5,776,486) on Super-Fluids CFL describes a method that is useful for the nanoencapsulation of paclitaxel and campothecin in aqueous liposomal formulations called Taxosomes and Camposomes , respectively. 

Since the discovery of vesicular structures, termed liposomes, by Alec Bangham, a tremendous amount of work on applications of liposomes has emerged. The use of small unilamellar liposomes as carriers of drugs for therapeutic applications has become one of the major fields in liposome research. The majority of these applications are based on the encapsulation of water-soluble molecules within the trapped volume of the liposomes. Long circulating poly(ethylene glycol) (PEG) modified liposomes with cytotoxic drugs doxorubicin, paclitaxel, vincristine, and lurtotecan are examples of clinically applied chemotherapeutic liposome formulations (1,2). 

Recently, easy to use paclitaxel formulation LEP-ETU , demonstrated bio-equivalence with Taxol (Bristol-Myers Squibb, New York, NY) and promising activity in Phase I trials. This is mainly due to a superior paclitaxel loading capacity in the liposome bilayer, at a maximum mole percent of about 3.5%. Similarly, paclitaxel has also been encapsulated in other modern formulations of cationic lipid complexes (MBT-0206) that have been shown to be bounded and internalized selectively by angiogenic tumoral endothelial cells after intravenous administration (29). 

Liposomes are predominantly used as carriers for hydrophilic molecules that are encapsulated within the aqueous inner volume which is confined by the lipid bilayer. These molecules generally do not interact with the lipid moiety of the vesicle. Long circulating liposomes modified with poly (ethylene glycol) (PEG) and other formulations carrying encapsulated cytotoxic drugs such as doxoru-bicine, paclitaxel, vincristine, lurtotecan and others are clinically approved chemotherapeutic liposome formulations (1-5). 

Kunstfeld R, Wickenhauser G, Michaehs U, Teifel M, Umek W, Naujoks K, Wolff K, Petzelbauer P. Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a humanized SCID mouse model. J Invest Dermatol. 2003 120 476-82. 

A biomedical or biotechnological application of such polymersome sttuctures is obvious because of their similarity to liposomes. On the one hand, hydrophobic drugs (e.g., doxombicin (DOX) or paclitaxel) and hydrophilic bioactive molecules (e.g., proteins, siRNA, DNA) can be encapsulated and then transported to and delivered at the target area (dmg delivery system). On the other hand, they can carry catalysts (e.g., enzymes) that are stabilized and protected by the polymersome membrane and selectively addressed when needed. Polymersomes, however, differ a lot from liposomes. Firstly, with... 

Supercritical fluids/gas/anti- solvent method PEG/PLA, PLGA, PVP, Poly(3-hydro- xybutyrate-co-3- hydroxjrvalerate) (PHBV), Ethylcellulose/ methylcellulose. Phospholipids, Liposomes, Itraconazole, Paclitaxel, Amphotericin B, Oxeglitazar, Beclomethasone, Naproxen, Low molecular weight heparins (LMWH) High encapsulation efficiencies, uniform particle size, easy to scale up, no toxicity due to complete solvent removal High cost of equipment, difficulty in finding proper emulsion solvents [97-99]... 

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