Preparation of Liposomal Raloxifene-Graphene Nanosheet and Evaluation of Its In Vitro Anticancer Effects

Background In current years, researchers have shown their prime interest in developing multifunctional drug delivery systems, especially against cancers, for effective anticancer outcomes. Methodology Raloxifene (RLX) loaded liposomal-graphene nanosheet (GNS) was developed. The novelty of this work was to enhance the solubilization of RLX and improvement of its bioavailability in the disease area. So, the selection of optimized formula design of experiment was implemented which produced the desired formula with the particle size of 156.333 nm. Further, encapsulation efficiency, in vitro release, and thermodynamic stability of optimized formulation were evaluated. The optimized formulation exhibited prolonged release of RLX for a longer period of 24 h, which can minimize the dose-related toxicity of the drug. Furthermore, optimized formulation demonstrated remarkable thermodynamic stability in terms of phase separation, creaming, and cracking. Results The cytotoxicity study on the A549 cell line exhibited significant ( P < .05) results in favor of optimized formulation than the free drug. The apoptotic activity was carried out by Annexin V staining and Caspase 3 analysis, which demonstrated remarkable promising results for optimized liposomal formulation. Conclusion From the findings of the study, it can be concluded that the novel optimized liposomal formulation could be pondered as a novel approach for the treatment of lung cancer.

Understanding Drug Delivery to the Brain Using Liposome-Based Strategies: Studies that Provide Mechanistic Insights Are Essential

Brain drug delivery may be restricted by the blood-brain barrier (BBB), and enhancement by liposome-based drug delivery strategies has been investigated. As access to the human brain is limited, many studies have been performed in experimental animals. Whereas providing interesting data, such studies have room for improvement to provide mechanistic insight into the rate and extent of specifically BBB transport and intrabrain distribution processes that all together govern CNS target delivery of the free drug. This review shortly summarizes BBB transport and current liposome-based strategies to overcome BBB transport restrictions, with the emphasis on how to determine the individual mechanisms that all together determine the time course of free drug brain concentrations, following their administration as such, and in liposomes. Animal studies using microdialysis providing time course information on unbound drug in plasma and brain are highlighted, as these provide the mechanistic information needed to understand BBB drug transport of the drug, and the impact of a liposomal formulations of that drug on BBB transport. Overall, these studies show that brain distribution of a drug administered as liposomal formulation depends on both drug properties and liposomal formulation characteristics. In general, evidence suggests that active transporters at the BBB, either being influx or efflux transporters, are circumvented by liposomes. It is concluded that liposomal formulations may provide interesting changes in BBB transport. More mechanistic studies are needed to understand relevant mechanisms in liposomal drug delivery to the brain, providing an improved basis for its prediction in human using animal data.

In-vitro evaluation of nano-liposomal formulation of Fluconazole and Amphotericin B against visceral leishmaniasis

Objectives: The aim of the present study was to compare the efficacy of a dual and single drug loaded nano-liposomal formulation of Amphotericin B and Fluconazole for the treatment of visceral leishmaniasis with plain drugs. Methods: We have formulated nano-liposomes (200-250 nm) from Amphotericin B and Fluconazole using dry film hydration method and have tested their efficacy on promastigotes and amastigotes of Leishmania donovani strain. Physicochemical characterization, entrapment study, stability study, in-vitro release study, in-vitro macrophagic uptake studies (Confocal microscopy) and in-vitro antileishmanial activity were evaluated for various formulations containing Amphotericin B and Fluconazole. Results: The in-vitro cellular uptake confocal studies revealed that NR-loaded AmpB + Flu nanoliposomes have enhanced cellular uptake of formulation. The in-vitro inhibition of promastigotes and amastigotes with liposome containing both Amphotericin B and Fluconazole was significantly more than with liposomes containing individual drugs. The IC50 and CC50 of AmpB + Flu nanoliposomes against promastigotes was found to be 3.308μg/mL and 73.48μg/mL respectively, while the IC50 against axenic and intramacrophagic amastigotes was found to be 3.412 and 3.7028μg/mL respectively. Conclusion: In conclusion, Liposomal formulation containing both Amphotericin B and Fluconazole had significantly greater efficacy than conventional combination and other formulation with individual drugs. Current dual drug loaded formulation may have a favourable safety profile, and if production costs are low, it may prove to be a feasible alternative to currently available therapy after in-vivo testing.

Formulation development of Temozolomide liposomal formulation in the treatment of Glioma

Temozolomide is an anti-cancer drug; it was encapsulated in liposomal intravenous application. To avoid the side effects and to target the drug to the specific site, we have formulated liposomal formulation of Temozolomide. The liposomal were prepared by dried thin film hydration technique using rotary evaporator with drug and Soya phosphatidyl choline as carrier. The prepared liposomes were characterized for size, shape, % entrapment efficiency, in-vitro drug release and physical stability. The evaluated batches showed good physicochemical characteristics. The maximum encapsulation efficiency of Temozolomide was achieved with formulation TMZ 6 with 40.19% and the in-vitro drug release is 64.94%. Based on the results it can be concluded that TMZ 6 was selected as optimized formulation and the optimized formulation Optimized formulation follows zero order release kinetics and follow super case II transport when it applied to Korsmeyer-Pepps model for mechanism of drug release.