Iliyas Khan1, Gaurav Joshi2, Kartik T Nakhate3, Raj Kumar2, Umesh Gupta4. 1. Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India. 2. Department of Pharmaceutical Sciences and Natural Products, School of Basic and Applied Sciences, Central University of Punjab, Bathinda, 151001, India. 3. Rungta College of Pharmaceutical Science and Research, Kohka, Bhilai, Chhattisgarh, 490024, India. 4. Department of Pharmacy, School of Chemical Sciences and Pharmacy, Central University of Rajasthan, Bandarsindri, Ajmer, Rajasthan, 305817, India. umeshgupta175@gmail.com.
Abstract
PURPOSE: Combinatorial approach can be beneficial for cancer treatment with better patient recovery. Co-delivery of natural and synthetic anticancer drug not only valuable to achieve better anticancer effectivity but also to ascertain toxicity. This study was aimed to co-deliver berberine (natural origin) and doxorubicin (synthetic origin) utilizing conjugation/encapsulation strategy through poly (lactic-co-glycolic acid) (PLGA) nanoparticles. METHODS: Doxorubicin was efficiently conjugated to PLGA via carbodiimide chemistry and the PLGA-doxorubicin conjugate (PDC) was used for encapsulation of berberine (PDBNP). RESULTS: Significant anti-proliferative against MDA-MB-231 and T47D breast cancer cell lines were observed with IC50 of 1.94 ± 0.22 and 1.02 ± 0.36 μM, which was significantly better than both the bio-actives (p < 0.05). The ROS study revealed that the PDBNP portrayed the slight increase in the reactive oxygen species (ROS) pattern in MDA-MB-231 cell line in a dose-dependent manner, while in T47D cells, no significant change in ROS was seen. PDBNP exhibits significant alteration (depolarization) in mitochondrial membrane permeability and arrest of cell cycle progression at sub G1 phase while the Annexin V/PI assay followed by confocal microscopy resulted into cell death mode to be because of necrosis against MDA-MB-231 cells. In vivo studies in Sprague Dawley rats revealed almost 14-fold increase in half life and a significant increase in plasma drug concentration. CONCLUSION: The overall approach of PLGA based co-delivery of doxorubicin and berberine witnessed synergetic effect and reduced toxicity as evidenced by preliminary toxicity studies.
PURPOSE: Combinatorial approach can be beneficial for cancer treatment with better patient recovery. Co-delivery of natural and synthetic anticancer drug not only valuable to achieve better anticancer effectivity but also to ascertain toxicity. This study was aimed to co-deliver berberine (natural origin) and doxorubicin (synthetic origin) utilizing conjugation/encapsulation strategy through poly (lactic-co-glycolic acid) (PLGA) nanoparticles. METHODS:Doxorubicin was efficiently conjugated to PLGA via carbodiimide chemistry and the PLGA-doxorubicin conjugate (PDC) was used for encapsulation of berberine (PDBNP). RESULTS: Significant anti-proliferative against MDA-MB-231 and T47D breast cancer cell lines were observed with IC50 of 1.94 ± 0.22 and 1.02 ± 0.36 μM, which was significantly better than both the bio-actives (p < 0.05). The ROS study revealed that the PDBNP portrayed the slight increase in the reactive oxygen species (ROS) pattern in MDA-MB-231 cell line in a dose-dependent manner, while in T47D cells, no significant change in ROS was seen. PDBNP exhibits significant alteration (depolarization) in mitochondrial membrane permeability and arrest of cell cycle progression at sub G1 phase while the Annexin V/PI assay followed by confocal microscopy resulted into cell death mode to be because of necrosis against MDA-MB-231 cells. In vivo studies in Sprague Dawley rats revealed almost 14-fold increase in half life and a significant increase in plasma drug concentration. CONCLUSION: The overall approach of PLGA based co-delivery of doxorubicin and berberine witnessed synergetic effect and reduced toxicity as evidenced by preliminary toxicity studies.
Entities:
Keywords:
PLGA-doxorubicin conjugate; berberine; encapsulation; in vivo pharmacokinetics; mitochondrial pathway; necrosis
Authors: Herbert Schneckenburger; Karl Stock; Marco Lyttek; Wolfgang S L Strauss; Reinhard Sailer Journal: Photochem Photobiol Sci Date: 2004-01 Impact factor: 3.982
Authors: Jianjun Cheng; Benjamin A Teply; Ines Sherifi; Josephine Sung; Gaurav Luther; Frank X Gu; Etgar Levy-Nissenbaum; Aleksandar F Radovic-Moreno; Robert Langer; Omid C Farokhzad Journal: Biomaterials Date: 2006-10-20 Impact factor: 12.479
Authors: Herman Burger; John A Foekens; Maxime P Look; Marion E Meijer-van Gelder; Jan G M Klijn; Erik A C Wiemer; Gerrit Stoter; Kees Nooter Journal: Clin Cancer Res Date: 2003-02 Impact factor: 12.531
Authors: I Craig Henderson; Donald A Berry; George D Demetri; Constance T Cirrincione; Lori J Goldstein; Silvana Martino; James N Ingle; M Robert Cooper; Daniel F Hayes; Katherine H Tkaczuk; Gini Fleming; James F Holland; David B Duggan; John T Carpenter; Emil Frei; Richard L Schilsky; William C Wood; Hyman B Muss; Larry Norton Journal: J Clin Oncol Date: 2003-03-15 Impact factor: 44.544
Authors: Jean-Marc Nabholtz; Carla Falkson; Daniel Campos; Janos Szanto; Miguel Martin; Stephen Chan; Tadeuz Pienkowski; Jerzy Zaluski; Tamas Pinter; Maciej Krzakowski; Daniel Vorobiof; Robert Leonard; Ian Kennedy; Nacer Azli; Michael Murawsky; Alessandro Riva; Pierre Pouillart Journal: J Clin Oncol Date: 2003-03-15 Impact factor: 44.544