Development and evaluation of co-formulated docetaxel and curcumin biodegradable nanoparticles for parenteral administration.
BACKGROUND
Technology for development of biodegradable nanoparticles encapsulating combinations for enhanced efficacy.


OBJECTIVE
To develop docetaxel (DTX) and curcumin (CRM) co-encapsulated biodegradable nanoparticles for parenteral administration with potential for prolonged release and decreased toxicity.


METHODS
Modified emulsion solvent-evaporation technique was employed in the preparation of the nanoparticles optimized by the face centered-central composite design (FC-CCD). The uptake potential was studied in MCF-7 cells, while the toxicity was evaluated by in vitro hemolysis test. In vivo pharmacokinetic was evaluated in male Wistar rats.


CONCLUSIONS
Co-encapsulated nanoparticles were developed of 219 nm size, 0.154 PDI, -13.74 mV zeta potential and 67.02% entrapment efficiency. Efficient uptake was observed by the nanoparticles in MCF-7 cells with decreased toxicity in comparison with the commercial DTX intravenous injection, Taxotere®. The nanoparticles exhibited biphasic release with initial burst release followed by sustained release for 5 days. The nanoparticles displayed a 4.3-fold increase in AUC (391.10 ± 32.94 versus 89.77 ± 10.58 μg/ml min) in comparison to Taxotere® with a 6.2-fold increase in MRT (24.78 ± 2.36 versus 3.58 ± 0.21 h).


CONCLUSIONS
The nanoparticles exhibited increased uptake, prolonged in vitro and in vivo release, with decreased toxicity thus exhibiting potential for enhanced efficacy.
a National Institute of Pharmaceutical Education and Research (NIPER) , Mohali , Punjab , India.
Harish
H
Pawar
a National Institute of Pharmaceutical Education and Research (NIPER) , Mohali , Punjab , India.
Shrikant Rameshrao
SR
Wankhade
a National Institute of Pharmaceutical Education and Research (NIPER) , Mohali , Punjab , India.
Dharmendra K
DK
Yadav
a National Institute of Pharmaceutical Education and Research (NIPER) , Mohali , Punjab , India.
Sarasija
S
Suresh
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003474:Curcumin / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D061986:MCF-7 Cells; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D043823:Taxoids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*
D000970:Antineoplastic Agents; D004337:Drug Carriers; D043823:Taxoids; D000077143:Docetaxel; D003474:Curcumin
Biodegradable nanoparticles; co-encapsulation; curcumin; docetaxel; face-centered design; prolonged release