ß-Artemether and Lumefantrine Dual Drug Loaded Lipid Nanoparticles: Physicochemical Characterization, Pharmacokinetic Evaluation and Biodistribution Study.

BACKGROUND: ß-artemether (BAT) and lumefantrine (LFT) combination therapies are well recognized for the treatment of malaria. However, the current conventional formulations have several drawbacks. OBJECTIVE: The study aims to develop novel lipid nanoparticles (LNP) for efficient delivery of BAT and LFT. METHODS: The LNP were prepared by solvent injection method and optimized by the Box-Behnken experimental design to achieve the desired particle size, maximum entrapment efficiency (EE), and percentage drug release. BAT and LFT in rat plasma were estimated by liquid chromatographytandem mass spectrometry (LC-MS/MS). RESULTS: Freeze-dried LNP comprised of 78.74% (w/w) lipid, 15.74% (w/w) surfactant, 3.93% (w/w) co-surfactant and 1.57% mannitol with respect to the total inactive components. Mean particle size and zeta potential were found to be 140.22 ± 1.36 nm and -35.23 mv, respectively. EE was 80.60 ± 3.85% for BAT and 69.64 ± 2.63% for LFT. The optimized formulation exhibited a biphasic release profile in phosphate buffer (pH 7.2). In vivo study revealed an increased bioavailability of BAT and LFT from dual drug loaded LNP compared to the pure drug solution. Moreover, the tissue distribution study confirmed the high uptake of both the drugs in the liver and spleen. CONCLUSION: The study demonstrated the potential use of the developed formulation for oral administration in the treatment of malaria.

Development and in vitro/in vivo evaluation of artemether and lumefantrine co-loaded nanoliposomes for parenteral delivery.

Combination therapy of artemether (ART) and lumefantrine (LUM) is well-established for the treatment of uncomplicated malaria worldwide. Nanoliposomes (NLs) encapsulating both drugs were prepared and freeze-dried. The lyophilized nanoliposomes exhibited high entrapment efficiency of artemether (66.18%), relatively low entrapment efficiency of lumefantrine (53.46%), low average size diameter (125.3 nm) and found to be stable at 4 °C for 60 days without significant change in mean particle diameter and drug entrapment efficiencies. In vitro drug release study has shown initial burst effect and then sustained release pattern over a time period of 30 h. In vivo toxicity study was examined by liver and kidney function test as well as histopathological examination. Nanoliposomes showed lower hemolytic potential (∼10%) compared to all the components when studied individually. There was no significant change (p > 0.05) in biochemical parametes between control and treated group of animals. Pharmacokinetic data of ART + LUM NLs showed higher the area under the plasma concentration-time curve (AUC) values and prolonged residence time of drug in the blood circulation compared with ART + LUM solution. The tissue distribution demonstrated high uptake of ART + LUM-NLs in RES organs particularly in liver and spleen. Biocompatibility was confirmed by hepato- and nephrotoxicity analysis showed no sign of fibrosis, fatty infiltration, centrilobular necrosis and lymphocyte infiltration confirmed the suitability of developed formulation for treatment of malaria.

Nano-Based Therapy for Treatment of Skin Cancer.

BACKGROUND: According to the World Health Organization, skin cancer is the most common malignancy for the population. Conventional skin cancer treatment includes surgery and chemotherapy, but many of the chemotherapeutic agents used present undesirable properties. There are a number of patents on topical nano formulation like nanoparticle (US9757453; US9457041), liposomes (US2018177726 (A1), has been covered in this review in the treatment of skin cancer. METHODS: Encapsulated drugs are advantageous due to such properties as high stability, better bioavailability, controlled drug release, a long blood circulation time, selective organ or tissue distribution, a lower total required dose, and minimal toxic side effects. Today, researchers are constantly developing new formulations to meet unmet needs in the delivery of therapeutic agents for cancer therapy and diagnosis, respectively. RESULTS: Of particular interest here are lipid-based nanoformulations that are formulated from varieties of lipid and other chemical components that act collectively to overcome biological barriers, in order to preferentially accumulate in or around disease-target cells for the functional delivery of therapeutic agents. The article deals with the recent development of nano-sized topical lipid formulation approaches to treat skin cancer. CONCLUSION: We focus especially on the topical lipid formulation approaches combined with chemotherapy, a field which specialises in target specificity, drug release control, and realtime monitoring with the goal being to diminish unwanted side effects and their severity, achieving a cheaper treatment and a generally more efficient chemotherapy.