Novel nanosystem to enhance the antitumor activity of lapatinib in breast cancer treatment: Therapeutic efficacy evaluation
| Autor: | Zhi-Qi Wang, Kai Liu, Shi-Jiang Wang, Bo Pang, Ping Liu, Wen-Shu Zuo, Zhi-Jun Huo |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Drug
Cancer Research media_common.quotation_subject Mice Nude Antineoplastic Agents Apoptosis Breast Neoplasms Pharmacology Lapatinib Polyethylene Glycols hybrid nanoparticles Mice Breast cancer breast cancer Phagocytosis Polylactic Acid-Polyglycolic Acid Copolymer Cell Line Tumor medicine Animals Humans Vitamin E Lactic Acid lapatinib Mononuclear Phagocyte System media_common Drug Carriers Mice Inbred BALB C business.industry Therapeutic effect General Medicine Original Articles medicine.disease Xenograft Model Antitumor Assays Tumor Burden Oncology Cancer cell Drug delivery drug delivery MCF-7 Cells Quinazolines Nanoparticles Female Drug carrier business Polyglycolic Acid medicine.drug |
| Zdroj: | Cancer Science |
| ISSN: | 1349-7006 1347-9032 |
| Popis: | The present study was performed to investigate the therapeutic performance of polymer-lipid hybrid nanoparticles towards the delivery of lapatinib (LPT) in breast cancers. We have successfully developed the lapatinib-loaded polymer-lipid hybrid nanosystem and showed its therapeutic potential in in vitro and in vivo models of breast cancer. The nanoformulations consisted of a polymeric core (poly[lactide-co-glycolide]-D-a-tocopheryl polyethylene glycol 1000 succinate [PLGA–TPGS]), which was then enveloped by a PEGylated lipid layer (DSPE-PEG) (PLPT) to maintain the structural integrity. The PLPT formulation controlled the drug release in pH 7.4 conditions and accelerated the release at pH 5.5 conditions. The PLPT showed a remarkable cellular internalization and efficiently killed the MCF-7 cancer cells in a time- and concentration-dependent manner. Moreover, LPT-loaded nanoparticles effectively induced apoptosis of cancer cells than compared to free LPT. Pharmacokinetic data suggested that nanoparticles could significantly enhance the blood circulation time of LPT by reducing the uptake by a reticuloendothelial system (RES). The prolonged blood circulation of PLPT could allow the preferential accumulation of drug in the tumor tissues. Importantly, PLPT significantly reduced the tumor burden of cancerous mice and effectively controlled the tumor cell proliferation. TUNEL assay further showed a greater apoptosis of tumor tissues in the PLPT treated mice group. Our results suggest that the use of a hybrid system may allow a decrease in the dosage regimen without the loss of therapeutic effect. Overall, lapatinib-loaded hybrid nanoparticles hold great potential for achieving an optimal therapeutic effect in breast cancer treatment. The present anticancer drug delivery system could be potentially applied for the treatment of other cancers. |
| Databáze: | OpenAIRE |
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