Understanding the role of lipids in drug transport is critical in cancer chemotherapy to overcome drug resistance. In this study, we isolated lipids from doxorubicin-sensitive (MCF-7) and -resistant (MCF-7/ADR) breast cancer cells to characterize the biophysical properties of membrane lipids (particularly lipid packing and membrane fluidity) and to understand the role of the interaction of cell membrane lipids with drug/nanocarrier on drug uptake and efficacy. Resistant cell membrane lipids showed significantly different composition and formed more condensed, less fluid monolayers than did lipids from sensitive cells. Doxorubicin, used as a model anticancer agent, showed a strong hydrophobic interaction with resistant cell membrane lipids but significantly less interaction, as well as a different pattern of interaction (i.e., ionic), with sensitive ones. The threshold intracellular doxorubicin concentration required to produce an antiproliferative effect was similar for both sensitive and resistant cell lines, suggesting that drug transport is a major barrier in determining drug efficacy in resistant cells. In addition to the biophysical characteristics of resistant cell membrane lipids, lipid-doxorubicin interactions appear to decrease intracellular drug transport via diffusion as the drug is trapped in the lipid bilayer. The rigid nature of resistant cell membranes also seems to influence endosomal functions that inhibit drug uptake when a liposomal formulation of doxorubicin is used. In conclusion, biophysical properties of resistant cell membrane lipids significantly influence drug transport, and hence drug efficacy. A better understanding of the mechanisms of cancer drug resistance is vital to developing more effective therapeutic interventions. In this regard, biophysical interaction studies with cell membrane lipids might be helpful to improve drug transport and efficacy through drug discovery and/or drug delivery approaches by overcoming the lipid barrier in resistant cells.
Nanocrystalline titania of different phases were produced by ambient condition sol process with phase control originating from alterations in experimental variables. The produced titania photocatalysts were characterized by use of x-ray diffraction, BET surface area, transmission electron microscopy and related to methyl orange degradation. The results showed that the photocatalytic activity of brookite and anatase phase titania samples to be greater than that of Degussa P-25 and rutile phase titania sample. In addition, brookite, due to surface area considerations, appears to be the most photocatalytically active phase of titania.
Poly(vinyl alcohol) (PVA) is commonly used as an emulsifier in the formulation of nanoparticles (NPs) comprising poly DL-lactide co-glycolide and polylactide-based biodegradable polymers for drug and gene delivery applications. A fraction of PVA remains associated with the NPs at the interface despite their repeated washing (residual PVA). We hypothesize that this residual PVA influences the interfacial properties of NPs and hence their biophysical interactions with membrane lipids. In this study, we formulated NPs using PVA of different molecular weights to determine the effects of the residual PVA on biophysical interactions of the formulated NPs with the endothelial cell model membrane using a Langmuir balance. Despite similar physical properties (particle size and zeta potential), NPs formulated with different PVA demonstrated significant variations in their intrinsic surface properties and biophysical interactions with the model membrane. This was evident from the difference in the surface pressure–area (π–A) isotherms prepared in the presence of different formulations of NPs and the change in surface pressure of the model membrane following interaction with NPs. The variation in the biophysical properties was observed even with the NPs formulated using the same molecular weight PVA but obtained from different lots. Since the interfacial properties of NPs can significantly influence NP interactions with cells and tissue, their biophysical characterization could prove to be an important parameter not only to obtain consistent results with NPs but also to optimize their properties for drug/gene delivery applications.
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