Intracellular availability of poorly soluble drugs from lipid nanocapsules
| Autor: | Achim Goepferich, Alexandra Haunberger, Marilena S. Bohley |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Biocompatibility
Drug Compounding Pharmaceutical Science 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Cell Line 03 medical and health sciences 0302 clinical medicine Nanocapsules Cyclosporin a Humans Particle Size Cell Proliferation Tube formation Chemistry Endothelial Cells General Medicine 021001 nanoscience & nanotechnology Lipids Vascular Endothelial Growth Factor Receptor-2 In vitro Endothelial stem cell Drug Combinations Drug Liberation Solubility Cyclosporine Itraconazole 0210 nano-technology Drug carrier Hydrophobic and Hydrophilic Interactions Intracellular Drug metabolism Biotechnology |
| Zdroj: | European Journal of Pharmaceutics and Biopharmaceutics. 139:23-32 |
| ISSN: | 0939-6411 |
| DOI: | 10.1016/j.ejpb.2019.03.007 |
| Popis: | Lipid nanocapsules (LNCs) are extensively used as drug carrier systems, due to their small size distribution, biocompatibility and ease of preparation. They are especially useful for lipophilic drugs to overcome physicochemical constraints that limit their efficacy, such as low solubility in aqueous media. The aim of this work was to investigate the relationship between the intracellular availability of poorly soluble drugs delivered via LNCs and their biological efficacy in cells in vitro. Cyclosporin A (CsA) with a logPOct = 4.3 (Lucangioli et al., 2003) and Itraconazole (It) with a logPOct = 6.2 (Bhardwaj et al., 2013) served as model lipophilic compounds, as they are highly promising candidates for the treatment of neovascular ocular diseases. Due to their lipophilic properties and the resulting preference for the oily core of LNCs, high encapsulation efficiencies were achieved. Drug-loaded LNCs with particle sizes around 50 nm were grafted with an αvβ3 integrin ligand (RGD) to optimize cellular uptake by human dermal microvascular endothelial cells. Even though RGD-LNCs showed excellent internalization, they exhibited insufficient inhibitory effects in vitro regarding endothelial cell proliferation, vascular endothelial growth factor expression, and tube formation in contrast to free drugs. This loss of efficacy could be explained by negligible intracellular availability of the poorly soluble drugs from LNCs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect