title: Improved efficacy of cisplatin in combination with a nano-formulation of pentacyclic triterpenediol.
abstract: Cisplatin is widely used for the treatment of various cancers including cervical, ovarian, lung and head and neck, however, its clinical success is limited owing to the dose-dependent adverse effects, mainly nephrotoxicity and neurotoxicity. In order to address this limitation, the present study was undertaken to investigate growth inhibitory effect of cisplatin in combination with a triterpenediol (3a, 24-dihydroxyurs-12-ene and 3a, 24-dihydroxyolean-12-ene, TPD) on human ovarian cancer cell line. Poly(dl-lactic-co-glycolic) acid nanoparticles loaded with TPD (TPD-PLGA-NPs) were successfully developed by emulsion solvent evaporation method. The TPD-PLGA-NPs were characterized for size distribution and zeta potential which was in order of 152.56±3.01nm and -17.36±0.37mV respectively. The morphological evaluation was carried out by transmission electron microscopy and the formulation was also characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The drug loading of the optimized formulation was 51.03±1.52μg/mg and the formulation exhibited sustained drug release profile. The in vitro cellular uptake study of coumarin-6 loaded PLGA nanoparticles in OVCAR-5 cells demonstrated a time dependent increase in uptake efficiency. Further, growth inhibitory effect of cisplatin was investigated in combination with TPD-PLGA-NPs. The combination index (CI) was <1, indicating a synergistic interaction. Further, at 75% of cell growth inhibition (ED75) the dose of cisplatin was reduced to 3.8 folds using this combination. The results indicated the potential of cisplatin and TPD-PLGA-NPs combination in order to reduce to dose limiting toxicities of the former.
authors: Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Noor
authors: N
authors: Alam
authors: Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Arem
authors: A
authors: Qayum
authors: Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Ashok
authors: A
authors: Kumar
authors: Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Vaibhav
authors: V
authors: Khare
authors: Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Parduman Raj
authors: PR
authors: Sharma
authors: Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Samar Singh
authors: SS
authors: Andotra
authors: Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
authors: Shashank K
authors: SK
authors: Singh
authors: Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: skoul@iiim.ac.in.
authors: Surinder
authors: S
authors: Koul
authors: Academy of Scientific and Innovative Research (AcSIR), Anusandhan Bhawan, 2 Rafi Marg, New Delhi 110001, India; Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: pngupta10@gmail.com.
authors: Prem N
authors: PN
authors: Gupta
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D053978:Pentacyclic Triterpenes / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D004337:Drug Carriers; D053978:Pentacyclic Triterpenes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D002945:Cisplatin
keywords: Boswellia serrata; Cisplatin; Drug combination; Nanoparticles; PLGA