The use of nanoparticles as drug delivery systems has increased in importance in the last decades. Despite the disadvantages of difficulty swallowing, gastric irritation, low solubility, and poor bioavailability, oral administration stands out as the most widely used route for therapeutic treatments, though it may not always be the most effective route. The effect of the first hepatic pass is one of the primary challenges that drugs must overcome to carry out their therapeutic effect. For these reasons, controlled-release systems based on nanoparticles synthesized from biodegradable natural polymers have been reported to be very efficient in enhancing oral delivery in multiple studies. Chitosan has been shown to have an extensive variability of properties and roles in the pharmaceutical and health fields; of its most important properties are the ability to encapsulate and transport drugs within the body and enhance the drug interaction with the target cells, which improves the efficacy of the encapsulated drugs. The physicochemical properties of chitosan give it the ability to form nanoparticles through multiple mechanisms, which will be addressed in this article. The present review article focuses on highlighting the applications of chitosan nanoparticles for oral drug delivery.
In situ-forming implants (ISFIs) based on poly(lactic-co-glycolic acid) (PLGA) offer a promising platform for long-acting parenteral drug delivery, enabling minimally invasive administration without surgical implantation. However, the development and clinical translation of PLGA-based ISFIs are hindered by formulation complexity, sensitivity to aterial variability, and limited predictability of drug release, particularly during early implant formation. Although previous reviews have described formulation components and release mechanisms, a comprehensive integration of Quality by Design (QbD) principles with a focus on risk prioritization remains absent. This review examines the application of QbD to solvent-exchange PLGA-based ISFIs, with an emphasis on identifying critical material attributes (CMAs) governing implant formation, burst release, and long-term release performance. Risk-based prioritization of CMAs and the role of design of experiments are systematically discussed. Special attention is given to burst release as a major CMA affecting safety, efficacy, and translational robustness. The evidence indicates that formulation-driven CMAs, such as polymer physicochemical properties, drug characteristics, and solvent selection, exert a greater influence on ISFI performance than process-related parameters. This review provides a structured perspective to support rational formulation design, improved reproducibility, and enhanced clinical translation of PLGA-based ISFI systems.
1 June 2022 in Journal of Pharmaceutical Innovation
The accurate determination and quantification of praziquantel are essential for optimizing its therapeutic effectiveness in treating schistosomiasis and neurocysticercosis, two significantly neglected tropical diseases. Its challenging physicochemical profile, extensive metabolism, and stereochemical complexity requires robust analytical methods for reliable quantification in clinical, veterinary, and pharmaceutical samples. This review provides a comprehensive and critical evaluation of analytical strategies used for PZQ determination, spanning fluorometric and radiometric assays, HPLC–UV, LC–MS, LC–MS/MS, and enantioselective chromatographic approaches. Particular emphasis is placed on the evolution toward highly sensitive LC–MS/MS methods and their alignment with contemporary regulatory expectations, including ICH M10 requirements. These advancements have significantly improved sensitivity, specificity, and reproducibility, which are crucial for pharmacokinetic, pharmacodynamic, and bioequivalence studies. Enantioselective methods for distinguishing PZQ enantiomers and metabolites are discussed. The aim of these innovations is to increase praziquantel bioavailability, improve patient adherence, and support its continued use in mass drug administration programs. Finally, the review highlights implementation challenges in resource-limited settings and proposes analytical models to expand global bioanalytical capacity. Together, these insights provide a structured foundation for selecting and developing high-quality, regulatory-compliant analytical methods for PZQ.
26 November 2024 in Mundo Nano. Revista Interdisciplinaria en Nanociencias y Nanotecnología
Los Sistemas Auto-Nanoemulsionables (SNEDDS) son formulaciones farmacéuticas basadas en nanotecnología que son de gran interés para fármacos poco solubles en agua (FPSA). Los SNEDDS están constituidos por una fase oleosa, un tensoactivo y un cotensoactivo que da lugar a una mezcla isotrópica, la cual forma nanoemulsiones al entrar en contacto con los fluidos intestinales. En la literatura se resalta la importancia de los SNEDDS para el desarrollo de nuevas formulaciones con FPSA. Los SNEDDS han demostrado ser formulaciones nanotecnológicas capaces de superar los desafíos asociados con la escasa solubilidad acuosa, la baja absorción y la limitada biodisponibilidad de FPSA, mejorando así las aplicaciones terapéuticas. Adicionalmente el proceso de manufactura es escalable y no involucra la inversión en equipo sofisticado a diferencia de otros sistemas nanoestructurados. Las tendencias en la modificación de SNEDDS incluyen su aplicación en nuevos tratamientos especializados, como la terapia génica, y la combinación con otros nanoacarreadores para superar limitaciones en estabilidad y eficacia. Los SNEDDS, impulsados por los avances en nanotecnología, no solo representan un avance en la formulación farmacéutica, sino que también marcan un camino hacia la mejora de la salud del paciente, destacándose como una clave para el futuro de la nanomedicina.
(1) Background: Modern pharmacology and regenerative medicine seek effective, safe drug delivery systems that allow for the controlled and sustained release of active ingredients; in situ forming implants (ISFIs) represent one such option. Systems based on poly(lactic-co-glycolic acid) (PLGA) and the solvent N-methyl-2-pyrrolidone (NMP) offer a safe, biodegradable, and non-invasive alternative. (2) Methods: ISFIs were prepared using NMP and PLGA at 50:50 and 85:15 ratios, combined with the supernatant obtained from umbilical cord Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs). Cellular utility, cytotoxicity, cell proliferation, and in vivo biocompatibility were evaluated using Annexin, 7AAD, Calcein, and PrestoBlue assays, as well as a murine model. Statiscal significance was determined using one way ANOVA followed by Tukey’s post hoc test for multiple comparisons, with the significance level at p < 0.05. (3) Results: Differences in cumulative release profile were observed between the PLGA/NMP 50:50 and 85:15 formulations. PLGA 50:50 exhibited higher early and cumulative release of WJ-MSC-supernatant-derived material, whereas PLGA 85:15 showed a slower and more sustained release profile. (4) Conclusions: Cell-free therapy delivered via PLGA 50:50/NMP ISFIs, incorporating associated immunomodulatory factors as supernatant’s WJ-MSCs, is suitable for an effective controlled-release system.