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While long-acting injectable treatments are gaining increasing interest in managing chronic diseases, the available drug delivery systems almost exclusively rely on hydrophobic matrixes, limiting their application to either hydrophobic drugs or large and hydrophilic molecules such as peptides. To address the technological lock for long-acting delivery systems tailored to small, hydrophilic drugs such as anticancer and antiviral nucleoside/nucleotide analogues, we have synthesized and characterized an original approach with a multi-scale structure: (i) a nucleotide (adenosine triphosphate, ATP) is first incorporated in hydrophilic chitosan-Fe(III) nanogels; (ii) these nanogels are then transferred by freeze-drying and resuspension into a water-free, hydrophobic medium containing PLGA and an organic solvent, N-methyl-2-pyrrolidone. We show that this specific association allows an injectable and homogeneous dispersion, able to form in situ implants upon injection in physiological or aqueous environments. This system releases ATP in vitro without any burst effect in a two-step mechanism, first as nanogels acting as an intermediate reservoir over a week, then as free drug over several weeks. In vivo studies confirmed the potential of such nanostructured implants for sustained drug release following subcutaneous injection to mice hock, opening perspectives for sustained and targeted delivery through the lymphatic system., (© 2024. Controlled Release Society.)

Introduction: Adenosine Triphosphate is a molecule with the function of generating energy, where high levels are directly related to cellular and muscular health. Oral supplementation appears as a possibility to guarantee such levels, and is normally consumed in capsules, which can be acute or chronic., Objectives: To verify the influence of a dose of ATP on muscular performance in adults., Methods: This is an acute, crossover, randomized, double-blind, placebo-controlled intervention study. 18 trained men were recruited, with an average age of 27.95 years. Two visits were made to the laboratory, where each of the protocols consisted of randomized supplementation of 400 mg of Peak ATP® or placebo, and 30 min later, five series were performed, where the first consisted of five repetitions and the following four of ten repetitions at 60° per second in knee extension and flexion on a Biodex® 4.0 isokinetic dynamometer, where the volunteers' muscle strength and resistance to fatigue were measured. For data analysis, data normality was assessed using Shapiro Wilk, the ANOVA repeated measures test with Bonferroni post hoc. To identify the size of the effect, the Cohen test was performed, and the statistical package used was SPSS 25 with an applied significance of p  < 0.05., Results: Acute supplementation was unable to achieve significant improvements in muscle strength indicators. The supplement delays drops in strength as the exercise progresses in knee extension compared to the placebo., Conclusions: An acute dose of 400 mg of ATP did not improve the volunteers' muscle strength indicators, but it was able to reduce fatigue levels as the exercise progressed, enabling greater performance for longer.