Since the revolutionary discovery that phospholipids can form closed bilayered structures in aqueous systems, liposomes have become a very interesting topic of research. Because of their versatility and amazing biocompatibility, the use of liposomes has been widely accepted in many scientific disciplines. Their applications, especially in medicine, have yielded breakthroughs with anticancer-drug carriers over the past few decades. Specifically, their easy preparation and various structural aspects have given rise to a broadly usable way to internalize biomolecules such as drugs, DNA, RNA and even imaging probes. This review article reports recent developments in liposomal drug delivery and gene delivery, and thoroughly covers the synthesis and different kinds of liposomal surface modification techniques that have resulted in higher stability and efficiency with respect to the use of liposomes in tumor cell targeting, site-specific release, and extending blood retention times.
Due to their efficient conversion of absorbed light energy to heat gold nanorods have been proved to be an amazing tool for minimally invasive photo-thermal cancer therapy. The present in vitro study demonstrates the ability of silica coated Au nanorods to function as a dual probe for cancer-cell therapy and imaging without any toxic side-effects. HeLa cells were incubated with silica coated Au nanorods and imaged inside the cell just after 1 hour of incubation by a dark field set up due to strong surface enhanced Raman scattering. To induce hyperthermia, silica coated Au nanorod incubated HeLa cells were illuminated with a diode laser (671 nm, 200 mW, 10 min). Cell destruction was observed even at a very low dose of nanorods, whereas none was observed in the absence of nanorods. Silica coated Au nanorods thus offer a promising, novel class of selective photo-thermal agents for cancer therapy and diagnosis.
As the existing therapeutic modalities for the treatment of cryptococcal meningitis (CM) have suboptimal efficacy, repurposing existing drugs for the treatment of CM is of great interest. The FDA-approved anthelmintic benzimidazoles, albendazole, mebendazole, and flubendazole, have demonstrated potent but variable in vitro activity against Cryptococcus neoformans, the predominant fungal species responsible for CM. We performed molecular docking studies to ascertain the interaction of albendazole, mebendazole, and flubendazole with a C. neoformans β-tubulin structure, which revealed differential binding interactions and explained the different in vitro efficacies reported previously and observed in this investigation. Despite their promising in vitro efficacy, the repurposing of anthelmintic benzimidazoles for oral CM therapy is significantly hampered due to their high crystallinity, poor pharmaceutical processability, low and pH-dependent solubility, and drug precipitation upon entering the intestine, all of which result in low and variable oral bioavailability. Here, we demonstrate that the anthelmintic benzimidazoles can be transformed into partially amorphous low-melting ionic liquids (ILs) with a simple metathesis reaction using amphiphilic sodium docusate as a counterion. In vitro efficacy studies on a laboratory reference and a clinical isolate of C. neoformans showed 2-to 4-fold lower IC 90 values for docusate-based ILs compared to the pure anthelmintic benzimidazoles. Furthermore, using a C. neoformans strain with green fluorescent protein (GFP)-tagged β-tubulin and albendazole and its docusate IL as model candidates, we showed that the benzimidazoles and their ILs reduce the viability of C. neoformans by interfering with its microtubule assembly. Unlike pure anthelmintic benzimidazoles, the docusate-based ILs showed excellent solubility in organic solvents and >30-fold higher solubility in bioavailability-enhancing lipid vehicles. Finally, the docusate ILs were successfully incorporated into SoluPlus, a self-assembling biodegradable polymer, which upon dilution with water formed polymeric micelles with a size of <100 nm. Thus, the development of docusate-based ILs represents an effective approach to improve the physicochemical properties and potency of anthelmintic benzimidazoles to facilitate their repurposing and preclinical development for CM therapy.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.