Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles.

Cannabidiol (CBD) is the most relevant nonpsychostimulant phytocompound found in Cannabis sativa. CBD has been extensively studied and has been proposed as a therapeutic candidate for neuroinflammation-related conditions. However, being a highly lipophilic drug, it has several drawbacks for pharmaceutical use, including low solubility and high permeability. Synthetic polymers can be used as drug delivery systems to improve CBD\'s stability, half-life, and biodistribution. Here, we propose using a synthetic polymer as a nanoparticulate vehicle for CBD (NPCBD) to overcome the pharmacological drawbacks of free drugs. We tested the NPCBD-engineered system in the context of ischemic events in a relevant oxygen and glucose deprivation (OGD) model in primary cortical cells (PCC). Moreover, we have characterized the inflammatory response of relevant cell types, such as THP-1 (human monocytes), HMC3 (human microglia), and PCC, to NPCBD and observed a shift in the inflammatory state of the treated cells after the ischemic event. In addition, NPCBD exhibited a promising ability to restore mitochondrial function after OGD insult in both HMC3 and PCC cells at low doses of 1 and 0.2 μM CBD. Taken together, these results suggest the potential for preclinical use.

The low percentage of recyclability of the polymeric materials obtained by olefin transition metal (TM) polymerization catalysis has increased the interest in their substitution with more eco-friendly materials with reliable physical and mechanical properties. Among the variety of known biodegradable polymers, linear aliphatic polyesters produced by ring-opening polymerization (ROP) of cyclic esters occupy a prominent position. The polymer properties are highly dependent on the macromolecule microstructure, and the control of stereoselectivity is necessary for providing materials with precise and finely tuned properties. In this review, we aim to outline the main synthetic routes, the physical properties and also the applications of three commercially available biodegradable materials: Polylactic acid (PLA), Poly(Lactic-co-Glycolic Acid) (PLGA), and Poly(3-hydroxybutyrate) (P3HB), all of three easily accessible via ROP. In this framework, understanding the origin of enantioselectivity and the factors that determine it is then crucial for the development of materials with suitable thermal and mechanical properties.

L-ornithine and L-glutamine are amino acids used for ammonia and nitrogen transport in the human body. Novel biodegradable synthetic poly(lactic-co-glycolic acid) derivatives were synthesized via conjugation with L-ornithine or L-glutamine, which were selected due to their biological importance. L-ornithine or L-glutamine was integrated into a PLGA polymer with EDC coupling reactions as a structure developer after the synthesis of PLGA via the polycondensation and ring-opening polymerization of lactide and glycolide. The chemical, thermal, and degradation property-structure relationships of PLGA, PLGA-L-ornithine, and PLGA-L-glutamine were identified. The conjugation between PLGA and the amino acid was confirmed through observation of an increase in the number of carbonyl carbons in the range of 170-160 ppm in the 13C NMR spectrum and the signal of the amide carbonyl vibration at about 1698 cm-1 in the FTIR spectrum. The developed PLGA-L-ornithine and PLGA-L-glutamine derivatives were thermally stable and energetic materials. In addition, PLGA-L-ornithine and PLGA-L-glutamine, with their unique hydrophilic properties, had faster degradation times than PLGA in terms of surface-type erosion, which covers their requirements. L-ornithine- and L-glutamine-linked PLGAs are potential candidates for development into biodegradable PLGA-derived biopolymers that can be used as raw materials for biomaterials.

Niclosamide (NIC) is a multifunctional drug that regulates various signaling pathways and biological processes. It is widely used for the treatment of cancer, viral infections, and metabolic disorders. However, its low water solubility limits its efficacy. In this study, poly(lactic-co-glycolic acid) (PLGA) and hyaluronic acid (HA), which exhibit good biocompatibility, biodegradability, and non-immunogenicity, were conjugated with niclosamide to prepare PLGA-HA-niclosamide polymeric nanoparticles (NIC@PLGA-HA) using microfluidic technology. The obtained microspheres had a uniform size distribution, with an average mean size of 442.0 ± 18.8 nm and zeta potential of -25.4 ± 0.41 mV, indicating their stable dispersion in water. The drug-loading efficiency was 8.70%. The drug-loaded microspheres showed sustained release behavior at pH 7.4 and 5.0, but not at pH 2.0, and the drug release kinetics were described by a quasi-first-order kinetic equation. The effect of the drug-loaded microspheres on the proliferation of Caco-2 cells was detected using the MTT assay. Hydrophilic HA-modified NIC@PLGA-HA microspheres prepared via microfluidic technology increased the cellular uptake by Caco-2 cells. Compared to the same concentration of NIC, the NIC@PLGA-HA microspheres demonstrated a stronger inhibitory effect on Caco-2 cells owing to the combined effect of PLGA, HA, and NIC. Therefore, the pH-responsive NIC@PLGA-HA microspheres synthesized using microfluid technology increased the solubility of NIC and improved its biological activity, thus contributing to the demand for intestinal drug carriers.

A glioma is the most common malignant primary brain tumor in adults and is categorized according to its growth potential and aggressiveness. Within gliomas, grade 4 glioblastoma remains one of the most lethal malignant solid tumors, with a median survival time less than 18 months. By encapsulating CPT-11 and oleic acid-coated magnetic nanoparticles (OMNPs) in poly(lactic-co-glycolic acid) (PLGA) nanoparticles, we first prepared PLGA@OMNP@CPT-11 nanoparticles in this study. After conjugating cetuximab (CET) with PLGA@OMNP@CPT-11, spherical PLGA@OMNP@CPT-11-CET nanoparticles with 250 nm diameter, 33% drug encapsulation efficiency, and 22% drug loading efficiency were prepared in a single emulsion/evaporation step. The nanoparticles were used for dual-targeted delivery of CPT-11 to U87 primary glioblastoma cells by actively targeting the overexpressed epidermal growth factor receptor on the surface of U87 cells, as well as by magnetic targeting. The physicochemical properties of nanoparticles were characterized in detail. CET-mediated targeting promotes intracellular uptake of nanoparticles by U87 cells, which can release four times more drug at pH 5 than at pH 7.4 to facilitate drug release in endosomes after intracellular uptake. The nanovehicle PLGA@OMNP-CET is cytocompatible and hemocompatible. After loading CPT-11, PLGA@OMNP@CPT-11-CET shows the highest cytotoxicity toward U87 compared with free CPT-11 and PLGA@OMNP@CPT-11 by providing the lowest drug concentration for half-maximal cell death (IC50) and the highest rate of cell apoptosis. In orthotopic brain tumor-bearing nude mice with U87 xenografts, intravenous injection of PLGA@OMNP@ CPT-11-CET followed by guidance with a magnetic field provided the best treatment efficacy with the lowest tumor-associated signal intensity from bioluminescence imaging.

UNASSIGNED: Currently, conventional treatments of hepatocellular carcinoma (HCC) are not selective enough for tumor tissue and lead to multidrug resistance and drug toxicity. Although sorafenib (SOR) is the standard first-line systemic therapy approved for the clinical treatment of HCC, its poor aqueous solubility and rapid clearance result in low absorption efficiency and severely limit its use for local treatment.
UNASSIGNED: Herein, we present the synthesis of biodegradable polymeric Poly (D, L-Lactide-co-glycolide) (PLGA) particles loaded with SOR (PS) by emulsion-solvent evaporation process. The particles are carefully characterized focusing on particle size, surface charge, morphology, drug loading content, encapsulation efficiency, in vitro stability, drug release behaviour and tested on HepG2 cells. Additionally, PLGA particles have been coupled on side emitting optical fibers (seOF) integrated in a microfluidic device for light-triggered local release.
UNASSIGNED: PS have a size of 248 nm, tunable surface charge and a uniform and spherical shape without aggregation. PS shows encapsulation efficiency of 89.7% and the highest drug loading (8.9%) between the SOR-loaded PLGA formulations. Treating HepG2 cells with PS containing SOR at 7.5 µM their viability is dampened to 40%, 30% and 17% after 48, 129 and 168 hours of incubation, respectively.
UNASSIGNED: The high PS stability, their sustained release profile and the rapid cellular uptake corroborate the enhanced cytotoxicity effect on HepG2. With the prospect of developing biomedical tools to control the spatial and temporal release of drugs, we successfully demonstrated the potentiality of seOF for light-triggered local release of the carriers. Our prototypical system paves the way to new devices integrating microfluidics, optical fibers, and advanced carriers capable to deliver minimally invasive locoregional cancer treatments.

UNASSIGNED: Tarsal plate repair is the major challenge of eyelid reconstruction for the oculoplastic surgeon. The ideal synthetic tarsal plate substitute should imitate the microstructure and mechanical strength of the natural eyelid. The aim of this work was to develop a novel bionic substitute for eyelid reconstruction.
UNASSIGNED: Three types of poly(lactic-co-glycolic acid) (PLGA) scaffolds (random, oriented, and azithromycin-loaded oriented scaffolds) were prepared using an improved thermal-induced phase separation technique. The microstructure of the scaffolds was examined by scanning electron microscopy. In vitro cytotoxicity was assessed using scaffold extracts. Fibroblast and primary rat meibomian gland epithelial cells (rMGCs) were cultured within the scaffolds, and their behavior was observed using fluorescence staining. Three types of PLGA scaffolds were implanted into rabbit eyelid defect in vivo to evaluate their inductive tissue repair function.
UNASSIGNED: We successfully fabricated three types of PLGA scaffolds with varying pore architectures, and the axially aligned scaffold demonstrated interconnected and vertically parallel channels. In vitro cytotoxicity tests using scaffold extracts revealed no apparent cytotoxicity. Fluorescence staining showed that both Fibroblast and rMGCs could adhere well onto the pore walls, with fibroblast elongating along the axially aligned porous structure. At 8 weeks post-implantation, all scaffolds were well integrated by fibrovascular tissue. The axially aligned scaffold groups exhibited faster degradation compared to the random scaffold group, with smaller fragments surrounded by mature collagen fibers.
UNASSIGNED: The study found that the axially aligned scaffolds could well support and guide cellular activities in vitro and in vivo. Moreover, the axially aligned scaffold group showed a faster degradation rate with a matched integration rate compared to the random scaffold group. The findings suggest that the oriented scaffold is a promising alternative for eyelid tarsal plate substitutes.

Bacterial vaginosis (BV) is a common condition that affects one-third of women worldwide. BV is characterized by low levels of healthy lactobacilli and an overgrowth of common anaerobes such as Gardnerella. Antibiotics for BV are administered orally or vaginally; however, approximately half of those treated will experience recurrence within 6 months. Lactobacillus crispatus present at high levels has been associated with positive health outcomes. To address the high recurrence rates following BV treatment, beneficial bacteria have been considered as an alternative or adjunct modality. This study aimed to establish proof-of-concept for a new long-acting delivery vehicle for L. crispatus. Here, it is shown that polyethylene oxide (PEO) fibers loaded with L. crispatus can be electrospun with poly(lactic-co-glycolic acid) (PLGA) fibers (ratio 1:1), and that this construct later releases L. crispatus as metabolically viable bacteria capable of lactic acid production and anti-Gardnerella activity. Probiotic-containing fibers were serially cultured in MRS (deMan, Rogosa, Sharpe) broth with daily media replacement and found to yield viable L. crispatus for at least 7 days. Lactic acid levels and corresponding pH values generally corresponded with levels of L. crispatus cultured from the fibers and strongly support the conclusion that fibers yield viable L. crispatus that is metabolically active. Cultures of L. crispatus-loaded fibers limited the growth of Gardnerella in a dilution-dependent manner during in vitro assays in the presence of cultured vaginal epithelial cells, demonstrating bactericidal potential. Exposure of VK2/E6E7 cells to L. crispatus-loaded fibers resulted in minimal loss of viability relative to untreated cells. Altogether, these data provide proof-of-concept for electrospun fibers as a candidate delivery vehicle for application of vaginal probiotics in a long-acting form.

OBJECTIVE: To investigate the floating, structural, and controlled-release characteristics of a floating poly(lactic-co-glycolic acid) (PLGA)-based controlled-release drug delivery system, and determine the feasibility of this drug delivery system for intravesical instillation.
METHODS: PLGA was dissolved in dimethylacetamide, then mixed with IR780 and doxorubicin (DOX) to prepare a drug delivery system capable of solidification and flotation on water at room temperature. Preparations of PLGA, PLGA+IR780, PLGA+DOX, and PLGA+IR780+DOX were formulated. Their floating characteristics in vivo and in vitro were investigated, along with their structural and controlled-release characteristics. Preparations of saline, DOX, and PLGA+IR780+DOX were also formulated; the content of DOX in bladder tissue delivered by each preparation was determined by fluorescence microscopy.
RESULTS: PLGA exhibited stable flotation in vivo and in vitro. A honeycomb structure was observed by scanning electron microscopy. When irradiated with a near-infrared laser, IR780 generated heat that vitrified PLGA, allowing controlled release of DOX from the drug delivery system. The PLGA+IR780+DOX preparation achieved the highest content of DOX in bladder tissue.
CONCLUSIONS: Our floating PLGA-based controlled-release drug delivery system exhibited a honeycomb stabilized structure and achieved controlled release when irradiated by a near-infrared laser, making it an ideal drug delivery system for intravesical instillation.