Polymeric nanoencapsulation of zaleplon into PLGA nanoparticles for enhanced pharmacokinetics and pharmacological activity

Abstract

Zaleplon (ZP) is a sedative and hypnotic drug used for the treatment of insomnia. Despite its potent anticonvulsant activity, ZP is not commonly used for the treatment of convulsion since ZP is characterized by its low oral bioavailability as a result of poor solubility and extensive liver metabolism. The following study aimed to formulate specifically controlled release nano‐vehicles for oral and parenteral delivery of ZP to enhance its oral bioavailability and biological activity. A modified single emulsification–solvent evaporation method of sonication force was adopted to optimize the inclusion of ZP into biodegradable nanoparticles (NPs) using poly (dl‐lactic‐co‐glycolic acid) (PLGA). The impacts of various formulation variables on the physicochemical characteristics of the ZP‐PLGA‐NPs and drug release profiles were investigated. Pharmacokinetics and pharmacological activity of ZP‐PLGA‐NPs were studied using experimental animals and were compared with generic ZP tablets. Assessment of gamma‐aminobutyric acid (GABA) level in plasma after oral administration was conducted using enzyme‐linked immunosorbent assay. The maximal electroshock‐induced seizures model evaluated anticonvulsant activity after the parenteral administration of ZP‐loaded NPs. The prepared ZP‐PLGA NPs were negatively charged spherical particles with an average size of 120–300 nm. Optimized ZP‐PLGA NPs showed higher plasma GABA levels, longer sedative, hypnotic effects, and a 3.42‐fold augmentation in oral drug bioavailability in comparison to ZP‐marketed products. Moreover, parenteral administration of ZP‐NPs showed higher anticonvulsant activity compared to free drug. Oral administration of ZP‐PLGA NPs achieved a significant improvement in the drug bioavailability, and parenteral administration showed a pronounced anticonvulsant activity.

Coriander (Coriandrum sativum L.) essential oil and oil-loaded nano-formulations as an anti-aging potentiality via TGFβ/SMAD pathway

“…The particle size, polydispersity index, and zeta potential of the prepared CEOLNs were measured using (Malvern Zetasizer Nano ZS90, UK) and all measurements were performed in triplicate at room temperature 48 , 49 .…”

Evaluation of Modified Date Palm (Phoenix dactylifera L.) Mucilage as a Potential Pharmaceutical Excipient

“…Aqueous extracts of Bistonia affinis and Malcolmia cabulica were used for the synthesis of medicinally effective AgNPs with a size range of 10 to 30 nm [48]. ZnO-NPs [49], CuO-NPs [50], and AuNPs [51] have been reported for pharmaceutical [52], pharmacological [53], and biological effects [54].…”

Investigating the Impact of Optimized Trans-Cinnamic Acid-Loaded PLGA Nanoparticles on Epithelial to Mesenchymal Transition in Breast Cancer

“… 16 The major drawbacks of most of the nanoparticle-based systems include low shelf‐life stability, the use of high concentrations of surfactant and cosurfactant, the liability of lipid oxidation and transformation, incompatibility with various active agents, and a limited drug loading efficiency. 17 In contrast, polymeric nanoparticles are more stable in vivo, with high drug loading capacities, and can release drugs in a controlled manner. 18 Polymeric nanoparticles which also appeared to be the best-fit for drug delivery in cancer therapy owing to their higher affinity for favored accumulation in certain solid tumors through the leaky endothelial tissue surrounding the tumor by enhanced permeability and retention (EPR) effect.…”