Begell House Inc.
Critical Reviews™ in Therapeutic Drug Carrier Systems
CRT
0743-4863
26
4
2009
Paclitaxel in Cancer Treatment: Perspectives and Prospects of its Delivery Challenges
333-372
10.1615/CritRevTherDrugCarrierSyst.v26.i4.10
Somnath
Singh
Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska
Alekha K.
Dash
Creighton University
nanoparticles
conjugation
complexation
cyclodextrins
prodrugs
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.
Pharmacoscintigraphy: A Blazing Trail for the Evaluation of New Drugs and Delivery Systems
373-426
10.1615/CritRevTherDrugCarrierSyst.v26.i4.20
Sanyog
Jain
Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar (Mohali), Punjab, India
Prateek
Dani
National Institute of Pharmaceutical Education and Research (NIPER), SAS Nagar (Mohali), Punjab
Rakesh Kumar
Sharma
Head, Division of Radiopharmaceuticals and Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Brig. SK Mazumdar Road, Delhi-110 054
gamma scintigraphy
diagnostic imaging
noninvasive imaging
site targeting
pharmacoscintigraphy
novel drug delivery systems
The drug development process is becoming increasingly sophisticated; as a result, the need for rapid and accurate means of predicting the in vivo behavior of drug products continues to grow. Preclinical in vivo evaluations involve the sacrifice of many animals and hence raise ethical issues. Therefore, noninvasive methods for assessing the in vivo behavior of drug products in animals have become an attractive alternative. Gamma scintigraphy is an established radiological-imaging technique that has been used in medical practice for the past several decades. Gamma scintigraphy is also used during clinical evaluations to map the formulation as it traverses the human body in real time. Combining this information with the pharmacokinetic data gives valuable information about the release and absorption mechanisms of drugs from their products. This technique also provides a handy tool for evaluating formulations at the preclinical and clinical stages of development for researchers who work in targeted drug delivery using novel drug carrier systems. The current review explores the use of pharmacoscintigraphy, a science that integrates gamma scintigraphy and conventional pharmacokinetics in the process of drug development.