Paclitaxel in cancer treatment: Perspectives and prospects of its delivery challenges

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Abstract

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.

Original languageEnglish
Pages (from-to)333-372
Number of pages40
JournalCritical Reviews in Therapeutic Drug Carrier Systems
Volume26
Issue number4
StatePublished - 2009

Fingerprint

Paclitaxel
Prodrugs
Neoplasms
Nanospheres
Therapeutics
Plasticizers
Lethargy
Cyclodextrins
Ointments
Emulsions
Microspheres
Vasodilation
Liposomes
Antineoplastic Agents
Hypotension
Solubility
Hypersensitivity
Respiration
Ethanol
Fatty Acids

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Pharmacology

Cite this

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AB - 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.

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