Topotecan–tamoxifen duple PLGA polymeric nanoparticles: Investigation of in vitro, in vivo and cellular uptake potential

• Published in: International journal of pharmaceutics 2014-10, Vol.473 (1-2), p.384-394
• Main Authors: Khuroo, Tahir, Verma, Devina, Talegaonkar, Sushama, Padhi, Santwana, Panda, Amulya K., Iqbal, Zeenat
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Hormonal - administration & dosage; Antineoplastic Agents, Hormonal - chemistry; Bioavailability; Biological Transport; Drug Carriers - administration & dosage; Drug Carriers - chemistry; Female; Humans; Intestinal Absorption; Lactic Acid - administration & dosage; Lactic Acid - chemistry; MCF-7; MCF-7 Cells; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; P-glycoprotein; Polyglycolic Acid - administration & dosage; Polyglycolic Acid - chemistry; Rats, Wistar; Tamoxifen; Tamoxifen - administration & dosage; Tamoxifen - chemistry; Topoisomerase I Inhibitors - administration & dosage; Topoisomerase I Inhibitors - chemistry; Topotecan; Topotecan - administration & dosage; Topotecan - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2014.07.022

[Display omitted] The dual drug loaded poly(dl-lactic-co-glycolic acid) (PLGA11Poly(dl-lactic-co-glycolic acid).) nanoparticles (TOP–TAM NPs22Topotecan HCl and tamoxifen citrate dual loaded nanoparticles.) concurrently delivering topotecan hydrochloride (TOP33Topotecan hydrochloride.) and tamoxifen citrate (TAM44Tamoxifen citrate.) 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-gp55P-glycoprotein.) 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 SEM66Scanning electron microscopy. and TEM77Transmission electron microscopy. technique. Similarly size of nanoparticles was found to be 151.2±1.6nm with 0.147±0.03 polydispersity index (PDI88Poly dispersity index.). 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 DSC99Differential scanning calorimetry. showed amorphous nature of both TOP and TAM. In an invitro 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.