No abstract

Artesunate (ART)-a well-known anti-malarial agent is also known to have potential anti-proliferative activities but its instability, poor aqueous solubility, and lack of relevant studies have limited its application as an effective anti-cancer drug. To overcome these problems, ART was loaded in poly (lactic-co-glycolic) acid (PLGA) nanoparticles using oil/water emulsion evaporation method. PLGA nanoparticles with small particle size and high entrapment efficiency were obtained. The PLGA nanoparticles were optimized by evaluating the effects of several formulation parameters on physicochemical properties of nanoparticles. The in vitro cytotoxicity of blank PLGA, free ART, and ART-PLGA on 3 human cancer cell lines viz. A549, SCC-7, and MCF-7 was conducted using MTT assay. The particles showed nanometric size (~170 nm), large entrapment efficiency (up to 83.4%), and excellent stability (evaluated for 1 month) after lyophilization with 5% mannitol. ART was dispersed inside particle core allowing a sustained release up to 48 h. The in vitro cytotoxicity results demonstrated strong activity of ART against cancer cell lines. The ART-PLGA formulation significantly reduced cell viability than the free ART. The formulation of ART loaded PLGA nanoparticles supported a potential application of ART as an anticancer agent.

Artesunate (ART)--a well-known hydrophobic anti-malarial agent was incorporated in a polymer-lipid hybrid nanocolloidal system for anti-cancer therapeutic. The lipid negatively charged nanoemulsion was formulated by modified hot homogenization method then covered with positively charged chitosan via electrostatic interaction to obtain chitosan-coated lipid nanocapsule (ART-CLN). Physical properties of the system were characterized in terms of size, charge, morphology, drug loading capacity, and physical state. In addition, anti-cancer activities were confirmed by conducting MTT assay for ART and ART-CLN on different cancer cell lines. Obtained ART-CLN after coating chitosan revealed positive charge (13.2 ± 0.87 mV), small particle size (160.9 ± 3.5 nm), and spherical shape. High drug entrapment efficiency (95.49 ± 1.13%) and sustained release pattern were observed. Moreover, the good cellular uptake was recorded by flow cytometry as well as confocal image. Finally, ART-CLN exhibited stronger anti-cancer activity than free ART on breast cancer cell lines (MCF-7, MDA-MB-231). These results suggested that by loading ART into lipid core of polymer-lipid hybrid carrier, the activity and physical stability of ART can be significantly increased for cancer chemotherapy.

Transdermal delivery provides numerous benefits over conventional routes of administration. However, this strategy is generally limited to a few molecules with specific physicochemical properties (low molecular weight, high potency, and moderate lipophilicity) due to the barrier function of the stratum corneum layer. Researchers have developed several physical enhancement techniques to expand the applications of the transdermal field; among these, microneedle technology has recently emerged as a promising platform to deliver therapeutic agents of any size into and across the skin. Typically, hydrophilic biomolecules cannot penetrate the skin by passive diffusion. Microneedle insertion disrupts skin integrity and compromises its protective function, thus creating pathways (microchannels) for enhanced permeation of macromolecules. Microneedles not only improve stability but also enhance skin delivery of various biomolecules. Academic institutions and industrial companies have invested substantial resources in the development of microneedle systems for biopharmaceutical delivery. This review article summarizes the most recent research to provide a comprehensive discussion about microneedle-mediated delivery of macromolecules, covering various topics from the introduction of the skin, transdermal delivery, microneedles, and biopharmaceuticals (current status, conventional administration, and stability issues), to different microneedle types, clinical trials, safety and acceptability of microneedles, manufacturing and regulatory issues, and the future of microneedle technology.

The aim of this study was to optimize the formulation of artesunate-loaded chitosan- (CS-) decorated poly(D,L-lactide-co-glycolide) acid (PLGA) nanoparticles as well as evaluate their characteristics. CS-to-PLGA mass ratio, pH of CS solution, and experimental temperature were optimized using response surface methodology to understand their effects on size and zeta potential of nanoparticles. The optimized formulation showed the close agreement between predicted and experimental values (all bias below 5%). The presence of CS was confirmed by positive surface charge and Fourier transform infrared spectroscopy. A spherical-like shape of particles was observed in range of small size around 190 nm. This CS layer restricted initial burst release of drug from carriers in phosphate buffer of pH 6.8. In addition, CS-coated NPs enhanced the intracellular uptake,in vitrocytotoxicity, and apoptosis-induced nuclei behaviors compared with CS-uncoated NPs as well as free drug in MCF-7 and A549 cancer cells.