Poly­(lactic-co-glycolic acid) (PLGA) is a versatile synthetic copolymer that is widely used in pharmaceutical applications. This is because it is well-tolerated in the body, and copolymers of varying physicochemical properties are readily available via ring-opening polymerization. However, native PLGA polymers are hard to track as drug delivery carriers when delivered to subcellular spaces, due to the absence of an easily accessible “handle” for fluorescent labeling. Here we show a one-step, scalable, solvent-free, synthetic route to fluorescent blue (2-aminoanthracene), green (5-aminofluorescein), and red (rhodamine-6G) PLGA, in which every polymer chain in the sample is fluorescently labeled. The utility of initiator-labeled PLGA was demonstrated through the preparation of nanoparticles, capable of therapeutic subcellular delivery to T-helper-precursor-1 (THP-1) macrophages, a model cell line for determining in vitro biocompatibility and particle uptake. Super resolution confocal fluorescence microscopy imaging showed that dye-initiated PLGA nanoparticles were internalized to punctate regions and retained bright fluorescence over at least 24 h. In comparison, PLGA nanoparticles with 5-aminofluorescein introduced by conventional nanoprecipitation/encapsulation showed diffuse and much lower fluorescence intensity in the same cells and over the same time periods. The utility of this approach for in vitro drug delivery experiments was demonstrated through the concurrent imaging of the fluorescent drug doxorubicin (λex = 480 nm, λem = 590 nm) with carrier 5-aminofluorescein PLGA, also in THP-1 cells, in which the intracellular locations of the drug and the polymer could be clearly visualized. Finally, the dye-labeled particles were evaluated in an in vivo model, via delivery to the nematode Caenorhabditis elegans, with bright fluorescence again apparent in the internal tract after 3 h. The results presented in this manuscript highlight the ease of synthesis of highly fluorescent PLGA, which could be used to augment tracking of future therapeutics and accelerate in vitro and in vivo characterization of delivery systems prior to clinical translation.

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Ceftriaxone is a third-generation cephalosporin antibiotic effective against many bacterial infections. However, owing to its instability in the gastrointestinal tract (GIT), it is administered by injections, which is an unfavourable route of administration. Therefore, the aim of this study was to formulate ceftriaxone into biodegradable and thermally stable polymeric blend microparticles that are suitable for oral delivery. The drug-loaded microparticles were prepared by the water-in-oil (W/O) emulsion method and consisted of starch and sodium alginate (NaAlg) as a polymeric matrix and glutaraldehyde (GA) as a cross-linking agent. Characterization of these particles using scanning electron microscopy (SEM) showed that the particles were spherical in shape with a smooth surface. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) of these particles showed no drug-polymer interactions. The highest percentage yield of particles was obtained at 3% polymer concentration. The particle size increased slightly after drug loading. The drug loading and entrapment efficiency appeared to increase with increasing polymer concentration. In vitro drug release at pH 1.2 and pH 7.4, revealed that drug release was below 20% at the acidic pH, while at pH 7.4, drug release of up to 85% was observed. The release mechanism followed first-order and Fickian diffusion patterns. Plasma concentration-time profiles were simulated for subcontinental Asian populations using commercial PBPK software, and the results suggest that microencapsulation of ceftriaxone sodium in a polymeric blend could represent a promising approach for controlled oral delivery of the drug, with enhanced absorption and bioavailability of the drug.