Premjeet Singh Sandhu1,2, Sarwar Beg3, Farhad Mehta1, Bhupinder Singh2,3, Piyush Trivedi4. 1. a 1 Rajeev Gandhi Technical University, School of Pharmaceutical Sciences , Bhopal, Madhya Pradesh, India pssandhu.rgtu@gmail.com. 2. b 2 Panjab University, UGC Centre of Excellence in Applications of Nanomaterials, Nanoparticles and Nanocomposites (Biomedical Sciences) , Chandigarh, India. 3. c 3 Panjab University, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies , Chandigarh, India. 4. d 4 Rajiv Gandhi Technical University, School of Pharmaceutical Sciences , Bhopal, Madhya Pradesh, India piyushtrivedi.rgtu@gmail.com.
Abstract
OBJECTIVES: This work describes the development and characterization of novel self-nanoemulsifying drug delivery systems (SNEDDS) employing polyunsaturated fatty acids for enhancing the oral bioavailability and anticancer activity of paclitaxel (PTX) by coadministration with curcumin (Cu). METHODS: Preformulation studies endorsed sesame oil, labrasol, and sodium deoxycholate as lipid surfactants and cosurfactants based on their solubility for the drugs and spontaneity of emulsification to produce nanoemulsions. Further, phase titration studies were performed to identify a suitable nanoemulsion region for preparing the SNEDDS formulation. RESULTS: The prepared formulations were characterized through in vitro, in situ, and in vivo studies to evaluate the biopharmaceutical performance. In vitro drug release studies showed 2.8- to 3.4-fold enhancement in the dissolution rate of both drugs from SNEDDS as compared with the pure drug suspension. Cell line studies revealed 1.5- to 2.7-fold reduction in the cytotoxicity on MCF-7 cells by plain PTX-SNEDDS and PTX-Cu-SNEDDS vis-à-vis the PTX-suspension. In situ intestinal perfusion studies revealed significant augmentation in permeability and absorption parameters of drug from PTX-Cu-SNEDDS over the plain PTX-SNEDDS and PTX-suspension (p < 0.001). In vivo pharmacokinetic studies also showed a remarkable improvement (i.e., 5.8- to 6.3-fold) in the oral bioavailability (Cmax and AUC) of the drug from PTX-SNEDDS and PTX-Cu-SNEDDS vis-à-vis the PTX-suspension. CONCLUSIONS: Overall, the studies corroborated superior biopharmaceutical performance of PTX-Cu-SNEDDS.
OBJECTIVES: This work describes the development and characterization of novel self-nanoemulsifying drug delivery systems (SNEDDS) employing polyunsaturated fatty acids for enhancing the oral bioavailability and anticancer activity of paclitaxel (PTX) by coadministration with curcumin (Cu). METHODS: Preformulation studies endorsed sesame oil, labrasol, and sodium deoxycholate as lipid surfactants and cosurfactants based on their solubility for the drugs and spontaneity of emulsification to produce nanoemulsions. Further, phase titration studies were performed to identify a suitable nanoemulsion region for preparing the SNEDDS formulation. RESULTS: The prepared formulations were characterized through in vitro, in situ, and in vivo studies to evaluate the biopharmaceutical performance. In vitro drug release studies showed 2.8- to 3.4-fold enhancement in the dissolution rate of both drugs from SNEDDS as compared with the pure drug suspension. Cell line studies revealed 1.5- to 2.7-fold reduction in the cytotoxicity on MCF-7 cells by plain PTX-SNEDDS and PTX-Cu-SNEDDS vis-à-vis the PTX-suspension. In situ intestinal perfusion studies revealed significant augmentation in permeability and absorption parameters of drug from PTX-Cu-SNEDDS over the plain PTX-SNEDDS and PTX-suspension (p < 0.001). In vivo pharmacokinetic studies also showed a remarkable improvement (i.e., 5.8- to 6.3-fold) in the oral bioavailability (Cmax and AUC) of the drug from PTX-SNEDDS and PTX-Cu-SNEDDS vis-à-vis the PTX-suspension. CONCLUSIONS: Overall, the studies corroborated superior biopharmaceutical performance of PTX-Cu-SNEDDS.