Liquid crystalline assembly for potential combinatorial chemo–herbal drug delivery to lung cancer cells
Open Access
- 1 January 2019
- journal article
- research article
- Published by Taylor & Francis Ltd in International Journal of Nanomedicine
- Vol. ume 14, 499-517
- https://doi.org/10.2147/ijn.s188335
Abstract
Background: Lung cancer is the most common cancer and the leading cause of total deaths worldwide. Its classified into two major types including non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) based on the origin of abnormal lung cells as well as the smoking status of the patient. NSCLC is the most common and aggressive type of lung cancer representing 80%–85% of all cases. Purpose: The aim of the study was to present lyotropic liquid crystalline nanoparticles (LCNPs) as promising carriers for co-delivery of the chemotherapeutic agent, pemetrexed (PMX) and the herbal drug, resveratrol (RSV) for effective lung cancer management. Methods: The proposed PMX-RSV-LCNPs were prepared by hydrotrope method. Hydrophobic ion pairing with cetyl trimethyl ammonium bromide (CTAB) was implemented to increase the encapsulation efficiency of the hydrophilic PMX up to 95%±3.01%. Results: The tailored PMX-RSV-LCNPs exhibited a particle size of 173±0.26 nm and biphasic release pattern with a relatively initial burst release within first 3–4 hour followed by sustained release up to 24 hours. Moreover, PMX-RSV-LCNPs manifested superior concentration and time dependent cytotoxicity profile against A549 lung cancer cells with IC50 4.0628 µg/mL. Besides, the enhanced cellular uptake profile based on bioadhesive properties of glyceryl monoolein (GMO) as well as energy independent (cholesterol dependent) pattern. In-vivo evaluations against urethane induced lung cancer bearing mice demonstrated the potentiality of PMX-RSV-LCNPs in tumor growth inhibition via inhibition of angiogenesis and induction of apoptosis. The results were supported by histopathological analysis and immunohistochemical Ki67 staining. Moreover, PMX-RSV-LCNPs displayed a promising safety profile via attenuating nephro- and hepatotoxicity. Conclusion: PMX-RSV-LCNPs elaborated in the current study hold a great promise for lung cancer treatment.Keywords
This publication has 56 references indexed in Scilit:
- Self-Assembled Multicompartment Liquid Crystalline Lipid Carriers for Protein, Peptide, and Nucleic Acid Drug DeliveryAccounts of Chemical Research, 2010
- The evidence for solid lipid nanoparticles mediated cell uptake of resveratrolInternational Journal of Pharmaceutics, 2010
- Pemetrexed in advanced non-small-cell lung cancerExpert Opinion on Pharmacotherapy, 2010
- Cancer Prevention and Treatment with Resveratrol: From Rodent Studies to Clinical TrialsCancer Prevention Research, 2009
- The Therapeutic Efficacy of Anti–Vascular Endothelial Growth Factor Antibody, Bevacizumab, and Pemetrexed against Orthotopically Implanted Human Pleural Mesothelioma Cells in Severe Combined Immunodeficient MiceClinical Cancer Research, 2007
- Targeting of nanoparticles to the clathrin-mediated endocytic pathwayBiochemical and Biophysical Research Communications, 2007
- Pemetrexed: biochemical and cellular pharmacology, mechanisms, and clinical applicationsMolecular Cancer Therapeutics, 2007
- FDA Drug Approval Summary: Pemetrexed for Injection (Alimta®) for the Treatment of Non-Small Cell Lung CancerThe Oncologist, 2005
- HPLC Method with UV Detection for the Determination of trans‐Resveratrol in PlasmaJournal of Liquid Chromatography & Related Technologies, 2005
- Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanismsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2004