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The Sojourn from Parenteral to Oral Taxanes using Nanocarrier Systems: A Patent Review

[ Vol. 10 , Issue. 1 ]

Author(s):

Rajneet K. Khurana, Mohit Mahajan, Teenu, Sonia Kapoor, Subheet Jain and Bhupinder Singh   Pages 44 - 58 ( 15 )

Abstract:


Natural diterpenoid taxanes and their semisynthetic analogues have already made an indelible mark in the chemotherapeutic world for treating various kinds of malignancies. However, due to the absence of any functional groups which could be ionized by pH alteration or which may participate in salt formation, these taxanes, exhibit low solubility. Parenteral administration of taxanes with solubilising agents such as Cremophor EL and Polysorbate 80 results in undesirable side effects like hypersensitivity reactions, myelosuppression and peripheral neuropathy. Nanoengineered drug delivery systems like nanoemulsions, nanocrystals, dendrimers, micelles, selfnanoemulsifying systems, liposomes, solid-lipid nanoparticles and biodegradable polymeric nanoparticles, in this regard, tend to surmount these ostensible challenges, when administered orally. The bare taxanes encounter several inadequacies, namely poor aqueous solubility, structural instability in physiological fluids, p-glycoprotein recognition, hepatic first-pass effect, gastrointestinal permeability, and Cytochrome P450 enzymatic metabolism, etc. In addition, nanoscaled oral delivery improves drug encapsulation, thus facilitating diffusion through intestinal epithelium, modification of pharmacokinetic and tissue distribution profile of the drug, eventually resulting in flexibility of dosing schedules, prevention of discomfort of the injection and hospitalization, and improved patient convenience. The current review paper endeavors to provide a bird’s eye view on the significant headway made on orally-administered nanosystems of taxanes and their analogues through patent applications published till date since its discovery.

Keywords:

Paclitaxel, docetaxel, P-glycoprotein, anticancer, SNEDDS, SLNs.

Affiliation:

University Institute of Pharmaceutical Sciences, Coordinator, UGC Centre of Advanced Studies, Coordinator, UGC Center for Excellence in Nano Applications, Panjab University, Chandigarh, 160014, India.



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