title: Synergistic anticancer efficacy of Bendamustine Hydrochloride loaded bioactive Hydroxyapatite nanoparticles: In-vitro, ex-vivo and in-vivo evaluation.
abstract: The present work evaluates the synergistic anticancer efficacy of bioactive Hydroxyapatite (HA) nanoparticles (HA NPs) loaded with Bendamustine HCl. Hydroxyapatite is a material with an excellent biological compatibility, a well-known fact which was also supported by the results of the Hemolytic studies and a high IC50 value observed in the MTT assay. HA NPs were prepared by the chemical precipitation method and loaded with the drug via physical adsorption. In-vitro release study was performed, which confirmed the sustained release of the drug from the drug loaded HA NPs. MTT assay, Cell Uptake and FACS studies on JURKAT E6.1 cell line and in-vivo pharmacokinetic studies in Wistar rats revealed that the drug loaded HA NPs could be easily internalized by the cells and release drug in a sustained manner. The drug loaded HA NPs showed cytotoxicity similar to the drug solution at 1/10th of the drug content, which indicates a possible synergism between the activity of the anticancer drug and calcium ions derived from the carrier. An increase in intracellular Ca(2+) ions is reported to induce apoptosis in cells. Tumor regression study in Balb/c mice Ehrlich's ascites model presented a similar synergistic efficacy. The drug solution was able to decrease the tumor volume by half, while the drug loaded HA NPs reduced the tumor size by 6 times.
authors.affiliation: Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi 110062, India.
authors.forename: Shindu C
authors.initials: SC
authors.lastname: Thomas
authors.affiliation: Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi 110062, India.
authors.forename: Harshita
authors.initials: H
authors.lastname: Sharma
authors.affiliation: Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi 110062, India.
authors.forename: Purnima
authors.initials: P
authors.lastname: Rawat
authors.affiliation: Nano Biotechnology Lab, Department of Zoology, Kirori Mal College, Delhi University, New Delhi 110007, India.
authors.forename: Anita K
authors.initials: AK
authors.lastname: Verma
authors.affiliation: Nano Biotechnology Lab, Department of Zoology, Kirori Mal College, Delhi University, New Delhi 110007, India.
authors.forename: Ankita
authors.initials: A
authors.lastname: Leekha
authors.affiliation: Nano Biotechnology Lab, Department of Zoology, Kirori Mal College, Delhi University, New Delhi 110007, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Nano Biotechnology Lab, Department of Zoology, Kirori Mal College, Delhi University, New Delhi 110007, India.
authors.forename: Aakriti
authors.initials: A
authors.lastname: Tyagi
authors.affiliation: Nano Biotechnology Lab, Department of Zoology, Kirori Mal College, Delhi University, New Delhi 110007, India.
authors.forename: Bahadur S
authors.initials: BS
authors.lastname: Gurjar
authors.affiliation: Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi 110062, India.
authors.forename: Zeenat
authors.initials: Z
authors.lastname: Iqbal
authors.affiliation: Nanoformulation Research Lab, Department of Pharmaceutics, Faculty of Pharmacy, Jamia Hamdard University, New Delhi 110062, India. Electronic address: stalegaonkar@gmail.com.
authors.forename: Sushama
authors.initials: S
authors.lastname: Talegaonkar
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000069461:Bendamustine Hydrochloride / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy* / Q000473:pathology; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D017886:Durapatite / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D017886:Durapatite; D000069461:Bendamustine Hydrochloride
keywords: Bendamustine Hydrochloride; Cancer therapy; Hydroxyapatite nanoparticles; Sustained delivery; Synergism