This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye’s surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel–water interactions, indicating that HA affects the water–polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain.
This study aimed to examine the impact of different surface properties of poly(lactic-co-glycolic) acid (PLGA) nanoparticles (P NPs) and PLGA-Poloxamer nanoparticles (PP NPs) on their in vivo biodistribution. For this purpose, NPs were formulated via nanoprecipitation and loaded with diphenylhexatriene (DPH), a fluorescent dye. The obtained NPs underwent comprehensive characterization, encompassing their morphology, technological attributes, DPH release rate, and thermodynamic properties. The produced NPs were then administered to wild-type mice via intraperitoneal injection, and, at scheduled time intervals, the animals were euthanized. Blood samples, as well as the liver, lungs, and kidneys, were extracted for histological examination and biodistribution analysis. The findings of this investigation revealed that the presence of poloxamers led to smaller NP sizes and induced partial crystallinity in the NPs. The biodistribution and histological results from in vivo experiments evidenced that both, P and PP NPs, exhibited comparable concentrations in the bloodstream, while P NPs could not be detected in the other organs examined. Conversely, PP NPs were primarily sequestered by the lungs and, to a lesser extent, by the kidneys. Future research endeavors will focus on investigating the behavior of drug-loaded NPs in pathological animal models.
The widespread use of synthetic plastics, as well as the waste produced at the end of their life cycle, poses serious environmental issues. In this context, bio-based plastics, i.e., natural polymers produced from renewable resources, represent a promising alternative to petroleum-based materials. One potential source of biopolymers is waste from the food industry, the use of which also provides a sustainable and eco-friendly solution to waste management. Thus, the aim of this work concerns the extraction of polysaccharide fractions from lemon, tomato and fennel waste. Characterizing the chemical–physical and thermodynamic properties of these polysaccharides is an essential step in evaluating their potential applications. Hence, the solubility of the extracted polysaccharides in different solvents, including water and organic solvents, was determined since it is an important parameter that determines their properties and applications. Also, acid-base titration was carried out, along with thermoanalytical tests through differential scanning calorimetry. Finally, the electrospinning of waste polysaccharides was investigated to explore the feasibility of obtaining polysaccharide-based membranes. Indeed, electrospun fibers are a promising structure/system via which it is possible to apply waste polysaccharides in packaging or well-being applications. Thanks to processing feasibility, it is possible to electrospin waste polysaccharides by combining them with different materials to obtain porous 3D membranes made of nanosized fibers.
Polymeric microparticles (MPs) designed for the intravitreal administration of therapeutic proteins result in a prolonged half-life in the vitreous and can delay or discourage the onset of adverse effects inevitably related to this route of administration. Hence, here we designed MPs composed of a polymeric blend based on poly(lactic-co-glycolic) acid and poloxamers, externally decorated with hyaluronic acid. The MPs are intended for intravitreal administration of bovine serum albumin. In detail, a systematic formulative study aiming to shed light on the complex relationship between protein release rate and MP degradation rate was carried out by means of calorimetric and gel permeation chromatography analyses. We found out that poloxamer addition caused a compact MP matrix, which led to a slight modification of the degradation kinetics and a reduction in the initial BSA initial release, which is of the utmost importance to ensure a relatively regular BSA release. It must also be underlined that for acid-labile molecules such as proteins, the poloxamer’s presence induced complex and hardly predictable effects on MP degradation/protein release, due to the dynamic balance between the time-evolving hydrophilicity of MPs and the influence of poloxamers themselves on the PLGA degradation rate.
5 December 2025 in International Journal of Pharmaceutics
Scalable nanoparticle manufacturing remains a key bottleneck in the clinical translation of RNA-based nanomedicines. In this study, we demonstrate the successful adaptation of a conventional emulsion-solvent diffusion protocol into an automated microfluidic workflow, illustrating its potential for streamlined and scalable nanoparticle production. Using the Sunshine™ microfluidic platform (Unchained Labs), we systematically optimized formulation and process parameters to produce siRNA-loaded hybrid lipid-polymer nanoparticles, featuring a poly(lactic-co-glycolic acid) (PLGA) core and a dipalmitoylphosphatidylcholine shell (mDPPC@PLGA hNPs). Optimised mDPPC@PLGA hNPs exhibited key technological features, matching or exceeding the quality of their benchtop equivalents (bDPPC@PLGA hNPs). Using poly(vinyl alcohol) (PVA) as a stabilizer, monodisperse mDPPC@PLGA hNPs with controlled size (<170 nm) and consistent zeta potential (-30 mV) were achieved with production yields ≥ 40 %. The ability of mDPPC@PLGA hNPs to effectively entrap and slowly release a siRNA targeting nuclear factor NF-κB (siNFκB) was successfully demonstrated. Structural characterization through thermodynamic and SAXS analyses confirmed that the microfluidic produced hNPs retained comparable internal architecture to their benchtop counterparts. Most notably, siNFκB-loaded mDPPC@PLGA hNPs resulted in effective in vitro downregulation of NFκB in lipopolysaccharide-stimulated A549 lung epithelial cells. Collectively, these results establish a novel and robust approach for the scalable fabrication of functional, siRNA-loaded hybrid nanoparticles via emulsion-solvent diffusion, leveraging a commercially available, automated microfluidic system with a serial chip configuration.