Combination Approach of YSA Peptide Anchored Docetaxel Stealth Liposomes with Oral Antifibrotic Agent for the Treatment of Lung Cancer

• DOI: 10.1021/acs.molpharmaceut.6b00187
• Publication Date: 2016-04-12T15:52:02Z
• Authors: Ketan Patel; Ravi Doddapaneni; Vasanthakumar Sekar; Nusrat Chowdhury; Mandip Singh
• Keywords: Telmisartan; Nanocarriers

Therapeutic efficacy of nanocarriers can be amplified by active targeting and overcoming the extracellular matrix associated barriers tumors. The aim present study was to investigate effect oral antifibrotic agent (telmisartan) on tumor uptake anticancer EphA2 receptor targeted liposomes. Docetaxel loaded PEGylated liposomes (DPL) functionalized with nickel chelated phospholipid were prepared using a modified hydration method. DPL incubated various concentrations histidine tagged specific peptide (YSA) optimize particle size, zeta potential, percentage YSA binding. Cellular studies endocytosis blockers revealed that caveolae dependent pathway major route for internalization anchored docetaxel (YDPL) in A549 lung cancer cell line. Hydrodynamic diameter potential optimized YDPL 157.3 ± 11.8 nm −3.64 mV, respectively. Orthotopic xenograft (A549) bearing athymic nude mice treated telmisartan (5 mg/kg) 2 days showed significantly (p < 0.05) higher tissues compared healthy tissue. Average weight + group 4.8- 3.8-fold lower than groups 0.05). Substantially expression protein, proliferating nuclear antigen (PCNA), MMP-9, collagen 1A level increased E-cadherin TIMP-1 levels immunohistochemistry Western blot analysis samples combination confirmed enhanced activity. Active ECM remodeling synergistically contributed orthotopic cancer.