title: Topotecan-tamoxifen duple PLGA polymeric nanoparticles: investigation of in vitro, in vivo and cellular uptake potential.
abstract: The dual drug loaded poly(dl-lactic-co-glycolic acid) (PLGA(1)) nanoparticles (TOP-TAM NPs(2)) concurrently delivering topotecan hydrochloride (TOP(3)) and tamoxifen citrate (TAM(4)) were developed to achieve synergism for the treatment of breast cancer by enhancing the permeation of TOP through the gut and the cells present in the breast. TAM acted as P-glycoprotein (P-gp(5)) inhibitor, reduced the side effects of individual drugs by reducing the dose. The NPs were prepared by double emulsion (w/o/w) method. The optimized TOP-TAM NPs were found to have smooth and spherical morphology by using SEM(6) and TEM(7) technique. Similarly size of nanoparticles was found to be 151.2 ± 1.6 nm with 0.147 ± 0.03 polydispersity index (PDI(8)). The percentage entrapment efficiency of 95.17 ± 3.57 and 57.77 ± 2.2 was found for TAM and TOP respectively. The lyophillized nanoparticles under DSC(9) showed amorphous nature of both TOP and TAM. In an in vitro release study the release of drugs from TOP-TAM NPs was found to follow the Higuchi pattern. The ex vivo gut permeation study revealed that the TAM enhanced the permeation of TOP and increased its bioavailability by 1.9 folds. The permeation and activity of combination of drugs were further confirmed by carrying out cell line studies on MCF-7 cells.
authors: Department of Pharmaceutics, Faculty of Pharmacy Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India; Product Development Cell-II, National Institute of Immunology, New Delhi 110067, India; Clinical Pharmacology and Pharmacokinetics, Ranbaxy Laboratories Limited, Gurgaon 122015, Haryana, India. Electronic address: tahirkhuroo11@gmail.com.
authors: Tahir
authors: T
authors: Khuroo
authors: Department of Pharmaceutics, Faculty of Pharmacy Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors: Devina
authors: D
authors: Verma
authors: Department of Pharmaceutics, Faculty of Pharmacy Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors: Sushama
authors: S
authors: Talegaonkar
authors: Department of Pharmaceutics, Faculty of Pharmacy Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India.
authors: Santwana
authors: S
authors: Padhi
authors: Product Development Cell-II, National Institute of Immunology, New Delhi 110067, India.
authors: Amulya K
authors: AK
authors: Panda
authors: Department of Pharmaceutics, Faculty of Pharmacy Jamia Hamdard, Hamdard Nagar, New Delhi 110062, India. Electronic address: ziqbaljh@yahoo.co.in.
authors: Zeenat
authors: Z
authors: Iqbal
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000737:chemistry; D001692:Biological Transport; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D005260:Female; D006801:Humans; D007408:Intestinal Absorption; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017208:Rats, Wistar; D013629:Tamoxifen / Q000008:administration & dosage / Q000737:chemistry; D059004:Topoisomerase I Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D019772:Topotecan / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004337:Drug Carriers; D059004:Topoisomerase I Inhibitors; D013629:Tamoxifen; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D019772:Topotecan
keywords: Acetonitrile (PubChem CID: 6342); Ammonium acetate (PubChem CID: 517165); Bioavailability; DMSO (PubChem CID: 679); Dichloromethane (PubChem CID: 6251); EDTA (PubChem CID: 6049); MCF-7; MTT tetrazolium (PubChem CID 64965); Mannitol (PubChem CID: 6251; Nanoparticles; P-glycoprotein; PLGA (PubChem CID: 23111554); Poly vinyl alcohol (PubChem CID: 23111554); Rolipram (PubChem CID: 5092); Tamoxifen; Tamoxifen citrate (PubChem CID: 2733525); Topotecan; Topotecan hydrochloride (PubChem CID: 60699)