LC-UV Determination of Melatonin from Chitosan Nanoparticles

An RP-LC method for the determination of melatonin with UV detection at 223 nm was developed and validated using a C(18) column at 25 A degrees C as stationary phase and a mixture of 0.1 M triethylammonium acetate at pH 7.0, and acetonitrile (70:30, V/V) as mobile phase. The method was linear (R (2) = 0.9997) over the concentration range of 0.05-8.00 mu g mL(-1). The RSD% of intra- and inter-day precision studies were less than 2% while the recovery% values were between 99 and 101%. The detection and quantitation limits were 9 and 31 ng mL(-1), respectively. The method was found to be specific, accurate, precise and sensitive for the determination of melatonin from chitosan nanoparticles

Development of Paclitaxel and Flurbiprofen Co-Loaded PLGA Nanoparticles: Understanding Critical Formulation and Process Parameters Using Plackett–Burman Design

Nano drug co-delivery system is a popular strategy for combined application of two or more anticancer and/or synergistic drugs. Synergistic effects of nonsteroidal anti-inflammatory drugs and anti-cancer drugs in cancer treatment are shown in the literature. This study aimed to screen and understand the critical formulation and process parameters in the preparation of flurbiprofen and paclitaxel co-loaded nanoparticles to develop an anti-cancer nano co-delivery system. With this aim, critical parameters were determined using the Plackett-Burman experimental design (DoE). Flurbiprofen and paclitaxel drug loading amounts were considered as critical quality attributes to control the effective drug loading ratio. Furthermore, average particle size and zeta potential were also defined as critical quality attributes in order to optimize passive drug targeting and colloidal stability. Surfactant type was determined as the most significant factor for the average particle size and zeta potential. For flurbiprofen and paclitaxel drug loading into the nanoparticles, amounts of both flurbiprofen and paclitaxel were determined as critical factors. Consequently, paclitaxel and flurbiprofen were efficiently loaded into nanoparticles, and the impact of the formulation variables was successfully screened by a DoE. By controlling the determined parameters, the therapeutic efficacy of co-loaded drug nanoparticles could be maximized in further studies

A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening

Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation’s ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach.Trials registration: NCT04975360

A small variation in average particle size of PLGA nanoparticles prepared by nanoprecipitation leads to considerable change in nanoparticles’ characteristics and efficacy of intracellular delivery

<p>In this study, it was aimed to investigate characteristics and intracellular delivery of two different-sized PLGA nanoparticles in ouzo region by considering number of nanoparticles. To determine the effect of formulation parameters on average particle size, Dil labeled nanoparticles were prepared using a three-factor, two-level full factorial statistical experimental design. PLGA₂₃₀ (230.8 ± 4.32 nm) and PLGA₁₆₀ (157.9 ± 6.16 nm) nanoparticles were obtained by altering polymer amount based on experimental design results and characterized. Same number of PLGA₂₃₀ and PLGA₁₆₀ nanoparticles per cell were applied onto HEK293 cells; then, cytotoxicity, uptake kinetics and mechanism were evaluated by flow cytometry and fluorescent microscopy. Also same weight of PLGA₂₃₀ and PLGA₁₆₀ nanoparticles were applied and cellular uptake of these nanoparticles was evaluated. It was found that PLGA₂₃₀ nanoparticles had higher encapsulation efficiency and slower dye release compared to PLGA₁₆₀ nanoparticles. When they were applied at same counts per cell, PLGA₂₃₀ nanoparticles displayed faster and higher intracellular dye transfer than PLGA₁₆₀ nanoparticles. On the other hand, PLGA₁₆₀ appeared to be a more effective vehicle than PLGA₂₃₀ when applied at the same weight concentration. It was also shown that for both nanoparticles, HEK293 cells employed macropinocytic, caveolae- and clathrin-mediated endocytic pathways.</p