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Introduction: Guided bone regeneration (GBR) technology has been widely used as a reliable method to address alveolar bone defects. To improve the clinical effects of GBR approach, there have been attempts to develop barrier membranes with enhanced regenerative properties. However, modifying the material and structure of GBR membranes to integrate physicochemical properties and biological activity remains challenging. The aim of this study was to develop a novel functionally graded bilayer membrane (FGBM) with a gradient structure and composition, and to evaluate its osteogenesis promotion effect for GBR. Methods: By combining the phase inversion method and electrospinning method, functionally graded bilayer membranes (FGBM) with gradient structure and composition of poly(lactic-co-glycolic acid) (PLGA), nano-hydroxyapatite (nHA), and gelatin were fabricated in this study. The physicochemical and biological properties of the prepared FGBM, including structural and morphological characterization, mechanical properties, in vitro biodegradation, cell behaviors, and in vivo osteogenic bioactivity, were comprehensively evaluated. Results: The findings demonstrated the successful fabrication of PLGA/nHA/gelatin FGBM with an asymmetric structure, exhibiting enhanced hydrophilic, mechanical, and degradation properties. The incorporation of gelatin not only improved the biological integration, but also enhanced the binding affinity between electrospun fiber layer and phase inversion layer. The FGBM with a 30% nHA mass fraction and a PLGA/gelatin mass ratio of 1:1 exhibited excellent barrier function and osteogenic bioactivities in vitro and in vivo. Discussion: This work demonstrated the potential of PLGA/nHA/gelatin FGBM in bone regeneration and provided valuable insight for the development of barrier membrane. [ABSTRACT FROM AUTHOR]

Introduction: Guided bone regeneration (GBR) technology has been widely used as a reliable method to address alveolar bone defects. To improve the clinical effects of GBR approach, there have been attempts to develop barrier membranes with enhanced regenerative properties. However, modifying the material and structure of GBR membranes to integrate physicochemical properties and biological activity remains challenging. The aim of this study was to develop a novel functionally graded bilayer membrane (FGBM) with a gradient structure and composition, and to evaluate its osteogenesis promotion effect for GBR. Methods: By combining the phase inversion method and electrospinning method, functionally graded bilayer membranes (FGBM) with gradient structure and composition of poly(lactic-co-glycolic acid) (PLGA), nanohydroxyapatite (nHA), and gelatin were fabricated in this study. The physicochemical and biological properties of the prepared FGBM, including structural and morphological characterization, mechanical properties, in vitro biodegradation, cell behaviors, and in vivo osteogenic bioactivity, were comprehensively evaluated. Results: The findings demonstrated the successful fabrication of PLGA/nHA/gelatin FGBM with an asymmetric structure, exhibiting enhanced hydrophilic, mechanical, and degradation properties. The incorporation of gelatin not only improved the biological integration, but also enhanced the binding affinity between electrospun fiber layer and phase inversion layer. The FGBM with a 30% nHA mass fraction and a PLGA/gelatin mass ratio of 1:1 exhibited excellent barrier function and osteogenic bioactivities in vitro and in vivo. Discussion: This work demonstrated the potential of PLGA/nHA/gelatin FGBM in bone regeneration and provided valuable insight for the development of barrier membrane. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by acute hypoxemic respiratory failure. Pneumonia and sepsis are the most common causes, turning ARDS into a critical public health problem. Despite recent advances in pharmacological strategies, clinical trials have not demonstrated a reduction in ARDS‐associated mortality. This is in part connected to the singularity of the pulmonary physiological barrier, which hampers drug delivery, specifically at distal areas. To this aim, the use of polymeric nanocarriers as a platform for the efficient delivery of therapeutics to the lungs by nebulization is introduced. Herein, poly(lactic‐co‐glycolic acid) (PLGA) nanocapsules (NCs) loaded with human serum albumin, as an inhalable nanotherapeutic are prepared. The production of stable NCs aerosols in the inhalable range is achieved using a commercial device, while the nanocarrier's physicochemical parameters are only minimally altered after nebulization. Importantly, in vivo studies with healthy and acute lung injury animals show that after inhalation, the NCs are homogeneously distributed throughout the lungs, arriving at the distal areas. The NCs are internalized by alveolar type II cells, avoiding macrophage‐mediated lung clearance. These features make the PLGA NCs excellent vehicles for noninvasive pulmonary delivery, facilitating a ready‐to‐be‐used nanomedicine. [ABSTRACT FROM AUTHOR]

Background: Diclofenac sodium (DS) and celecoxib (CEL) are primary anti-inflammatory agents used in the treatment of osteoarthritis (OA). Formulating these drugs into extended-release versions can effectively address the issue of multiple daily doses. In this study, we designed and synthesized a novel poly(lactic-co-glycolic acid) (PLGA) nanoliposome as a dual-drug delivery sustained-release formulation (PPLs-DS-CEL) to achieve long-lasting synergistic treatment of OA with both DS and CEL. Methods: PPLs-DS-CEL was synthesized by the reverse evaporation method and evaluated for its physicochemical properties, encapsulation efficiency, drug release kinetics and biological properties. A rat OA model was established to assess the therapeutic efficacy and biosafety of PPLs-DS-CEL. Results: The particle size of PPLs-DS-CEL was 218.36 ± 6.27 nm, with a potential of 32.56 ± 3.28 mv, indicating a homogeneous vesicle size. The encapsulation of DS and CEL by PPLs-DS-CEL was 95.18 ± 4.43% and 93.63 ± 5.11%, with drug loading of 9.56 ± 0.32% and 9.68 ± 0.34%, respectively. PPLs-DS-CEL exhibited low cytotoxicity and hemolysis, and was able to achieve long-lasting synergistic analgesic and anti-inflammatory therapeutic effects in OA through slow release of DS and CEL, demonstrating good biosafety properties. Conclusion: This study developed a novel sustained-release nanoliposomes formulation capable of co-loading two drugs for the long-acting synergistic treatment of OA. It offers a new and effective therapeutic strategy for OA treatment in the clinic settings and presents a promising approach for drug delivery systems. [ABSTRACT FROM AUTHOR]

Yu-Chi Wang,1,* Meng-Ting Cai,1,* Ming-Hong Chen,2,3 Fu-I Tung,4,5 Mei-Hsiu Chen,6,7 Tse-Ying Liu1 1Department of Biomedical Engineering, National Yang Ming Chiao Tung University, Taipei, 112304, Taiwan; 2Division of Neurosurgery, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, 220216, Taiwan; 3Department of Electrical Engineering, Yuan Ze University, Taoyuan City, 320315, Taiwan; 4Department of Orthopaedics, Yang-Ming Branch, Taipei City Hospital, Taipei, 111024, Taiwan; 5Department of Health and Welfare, College of City Management, University of Taipei, Taipei, 111036, Taiwan; 6Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, 220216, Taiwan; 7Department of Biomedical Engineering, Ming Chuang University, Taoyuan, 333, Taiwan*These authors contributed equally to this workCorrespondence: Tse-Ying Liu; Mei-Hsiu Chen, Email tyliu5@nycu.edu.tw; michelle8989@gmail.comPurpose: Osteoporosis, characterized by reduced bone mass and structural deterioration, poses a significant healthcare challenge. Traditional treatments, while effective in reducing fracture risks, are often limited by side effects. This study introduces a novel nanocomplex, europium (Eu) ions-doped superparamagnetic iron oxide (SPIO) nanocrystals encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanospheres, abbreviated as SPIO:Eu@PLGA nanospheres, as a potential therapeutic agent for osteoporosis by modulating macrophage polarization, enhancing osteoblast differentiation and inhibiting osteoclastogenesis.Methods: SPIO and SPIO:Eu nanocrystals were synthesized through pyrolysis and encapsulated in PLGA using an emulsification method. To evaluate the impact of SPIO:Eu@PLGA nanospheres on macrophage reprogramming and reactive oxygen species (ROS) production, flow cytometry analysis was conducted. Furthermore, an ovariectomized (OVX) rat model was employed to assess the therapeutic efficacy of SPIO:Eu@PLGA nanospheres in preventing the deterioration of osteoporosis.Results: In vitro, SPIO:Eu@PLGA nanospheres significantly attenuated M1 macrophage activation induced by lipopolysaccharides, promoting a shift towards the M2 phenotype. This action is linked to the modulation of ROS and the NF-κB pathway. Unlike free Eu ions, which do not achieve similar results when not incorporated into the SPIO nanocrystals. SPIO:Eu@PLGA nanospheres enhanced osteoblast differentiation and matrix mineralization while inhibiting RANKL-induced osteoclastogenesis. In vivo studies demonstrated that SPIO:Eu@PLGA nanospheres effectively targeted trabecular bone surfaces in OVX rats under magnetic guidance, preserving their structure and repairing trabecular bone loss by modulating macrophage polarization, thus restoring bone remodeling homeostasis. The study underscores the critical role of Eu doping in boosting the anti-osteoporotic effects of SPIO:Eu@PLGA nanospheres, evident at both cellular and tissue levels in vitro and in vivo.Conclusion: The inclusion of Eu into SPIO matrix suggests a novel approach for developing more effective osteoporosis treatments, particularly for conditions induced by OVX. This research provides essential insights into SPIO:Eu@PLGA nanospheres as an innovative osteoporosis treatment, addressing the limitations of conventional therapies through targeted delivery and macrophage polarization modulation.Keywords: osteoporosis, macrophage polarization, osteoblast, osteoclast, nanocrystals, poly(lactic-co-glycolic acid)

In this study, the electrospinning technique was employed to create a nanofiber membrane by stretching an organic polymer into nanofibers under a high electric field. Metronidazole (MNZ) at a concentration of 3 wt% was loaded into a poly(lactic-co-glycolic acid) (PLGA) and silk fibroin (SF)-blended nanofiber membrane. This formulation aims to achieve effective and sustained drug release, enabling the eradication of bacteria for the efficient treatment of periodontitis. Results demonstrated that SF interacted with PLGA molecules, forming dense and uniform nanofibers with a diameter of 570 nm. Excessive SF molecules tended to aggregate, leading to an increased particle size, with the interaction between MNZ and SF contributing to adhesion. The composition of MNZ, SF, and PLGA formed a physical chimera without any chemical reactions. Moreover, as the SF content increased, the tensile properties of the membrane gradually improved. Concurrently, the in vitro degradation rate increased with higher SF content. Among the various groups tested, the 3 wt% MNZ/PLGA/SF 2:1 membrane exhibited superior drug release characteristics, with 71.76% release within 24 h. This formulation demonstrated excellent antibacterial properties, indicated by a bacterial inhibition diameter of 13.5 mm, noteworthy hydrophilicity with a contact angle of 44.3°, and favorable biocompatibility. The membrane holds significant application value in regenerative engineering and drug delivery systems, showcasing substantial potential for the treatment of periodontitis.

Abstract 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 (

Platelet-rich plasma (PRP) and hyaluronic acid (HA) injection is commonly used for the treatment of osteoarthritis. However, the immediate bolus release of growth factors from PRP and inability of HA to stay in situ limit their beneficial therapeutic effects. An injectable, biocompatible, and thermoresponsive hydrogel (mPEG-PLGA-BOX block copolymer) is applicable for a long-term ultrasound-triggered lyophilized platelet (LP) release. In this study, an US-controlled release thermoresponsive hydrogel system loaded with LPs was evaluated for its long-term pharmacokinetics in a dry culture chamber at 37 °C. At 0.5 wt% constituent ratio of the LP-loaded hydrogels (0.2 ± 0.6 mV positively charged, which would be suitable for the treatments of negatively charged cartilages), the release amount of growth factors (PDGF-B and TGFβ-1) from the hydrogel could be increased to ∼300-folds in the presence of US (1 MHz, 0.4 W/cm2, 5% duty cycle, 5 min) compared to the amount in the absence of US during the 2 weeks of evaluation period. In comparison to 0.5 wt% of the LP-loaded HA (−2.4 ± 1.1 mV negatively charged), which had only a 5-day release ability, the US-controlled release thermoresponsive hydrogel system may be a more suitable platform for diseases that needed long-term treatments. [ABSTRACT FROM AUTHOR]

Controlled drug release (CDR) is a significant field of research in medical sciences due to its numerous clinical advantages over traditional methods. Encapsulation of a drug in a polymeric matrix is common technique to achieve CDR. In this study, drug‐polymer particles are prepared using poly(lactic‐co‐glycolic acid) (PLGA) as the polymer and curcumin (CUR) as model drug. Two different methods, electrospray and nanoprecipitation, are used to prepare the particles, and optimal samples in each process are selected based on size and polydispersity index (PDI). Samples are characterized using various tests, and entrapment efficiency (EE%) and drug loading (DL%) are calculated using UV spectroscopy. The results showed that nanoprecipitated and electrosprayed PLGA particles successfully encapsulated CUR, with higher encapsulation efficiency (93.2%) and loading capacity (7.2%) for electrosprayed particles. The in vitro drug release showed that electrospray particles have a slower release rate due to higher encapsulation efficiency. The electrospray method turned out to be more viable for synthesizing these polymer‐drug particles due to smaller particle size, lower PDI, higher entrapment efficiency, and drug loading percentage. Finally, the antibacterial behavior of the particles proved that prepared particles provide excellent antibacterial efficacy (99.9%) and can be used as drug delivery systems. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Oxidation of glycerol to lactic and glycolic acids is one of the most sought-after upgrades for this waste product in the biodiesel industry. These renewable glycerol-based hydroxy—carboxylic acid products are valuable monomers for the synthesis of new generation biodegradable polymers. In this work, a practically no-cost catalyst was prepared by using electrode coatings in 18,650 type Li-ion cells found in a spent DELL laptop battery. The combined cathode and anode coatings collected from Li-ion cells were pyrolyzed at 600 °C in air for 30 min. to prepare the catalyst with formula LiNi0.03Mn0.02Co0.11O0.85/C. Oxidation of glycerol using 25 mg/mmol catalyst in 0.50 M aqueous NaOH, under 3.4 atm. O2, 230 °C, 4 h. gave the highest yields of lactic and glycolic acids, 54 and 41%, respectively. Next, this hydroxy acid mixture was directly polymerized using p-toluene sulfonic acid—SnCl2 catalyst in refluxing xylene to give poly(lactic-co-glycolic acid) with Mw = 8017, Mw/Mn = 1.435, Tg = 41 °C, Tm = 182 °C and in 74% yield. [ABSTRACT FROM AUTHOR]

The use of biomaterials in additive manufacturing (AM) of medical devices has gained significant attention over the years, especially in areas such as wound care and orthopedics. This study aims to investigate the performance of bioresorbable peptide-incorporated polymers produced for fused deposition modelling (FDM) process. Herein, we report FDM 3D Printing process of bioactive polymers comprising polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) or polylactic acid (PLA) or blended with peptide–containing brush copolymers bearing similar synthetic polymer side chains. Mechanical, thermal and rheological properties of the materials were carried out and we report that the incorporation of bioactive polymers into these biodegradable polymers does not result in significant changes to glass transition temperature, melt temperature, tensile properties of the base polymers. However, it was observed that flexural and rheological properties altered significantly. This study provides an insight into the thermomechanical performance of bioresorbable peptide-incorporated polymers for FDM utilization which allows for their use potential in medical device fabrication.

Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by acute hypoxemic respiratory failure. Pneumonia and sepsis are the most common causes, turning ARDS into a critical public health problem. Despite recent advances in pharmacological strategies, clinical trials have not demonstrated a reduction in ARDS‐associated mortality. This is in part connected to the singularity of the pulmonary physiological barrier, which hampers drug delivery, specifically at distal areas. To this aim, the use of polymeric nanocarriers as a platform for the efficient delivery of therapeutics to the lungs by nebulization is introduced. Herein, poly(lactic‐co‐glycolic acid) (PLGA) nanocapsules (NCs) loaded with human serum albumin, as an inhalable nanotherapeutic are prepared. The production of stable NCs aerosols in the inhalable range is achieved using a commercial device, while the nanocarrier's physicochemical parameters are only minimally altered after nebulization. Importantly, in vivo studies with healthy and acute lung injury animals show that after inhalation, the NCs are homogeneously distributed throughout the lungs, arriving at the distal areas. The NCs are internalized by alveolar type II cells, avoiding macrophage‐mediated lung clearance. These features make the PLGA NCs excellent vehicles for noninvasive pulmonary delivery, facilitating a ready‐to‐be‐used nanomedicine.

Wang L, Li D, Hao Y, et al. Int J Nanomedicine. 2017;12:3059-3075. The authors have advised Figures 9 and 11 on pages 3070 and 3071, respectively, are incorrect. The H&E staining image of tumor tissue in the PLGA/DTX@MnO2 group in Figure 9C and the X-ray CT images in Figure 11C were inadvertently misused during data acquisition. The correct Figure 9 is as follows. Figure 9 Inhibition of tumor growth in vivo by the drug delivery system.Abbreviations: H&E, hematoxylin and eosin; AuNR, gold nanorod; DTX, docetaxel; MnO2, manganese dioxide; PLGA, poly(lactic-co-glycolic acid); RF, radiofrequency.Notes: (A) Relative volumes of tumor-bearing mice; (B) body weight of the mice models (mean ± standard deviation; n=6); (C) H&E-stained tumor tissue sections: (a) control, (b) DTX, (c) PLGA/DTX@MnO2, (d) PLGA/DTX@MnO2 + RF, (e) PLGA/AuNR/DTX@MnO2, and (f) PLGA/AuNR/DTX@MnO2 + RF. The correct Figure 11 is as follows. Figure 11 Dual-mode imaging in vivo.Abbreviations: MR, magnetic resonance; CT, computed tomography.Notes: (A, B) T1-weighted MR images; (C) X-ray CT images: (a) control; (b) 4 h; (c) 8 h. The authors apologize for these errors and advise they do not affect the results and conclusions of the paper.

Obstruct pharmacokinetics and low bioavailability of diosgenin (DG) and emodin (ED) are major limitations for their therapeutic success in several inflammatory diseases. Nanoencapsulation of both drugs will promisingly overcome these limitations. Herein, polylactic-co-glycolic acid (PLGA) was used for nanoformulation of diosgenin- and emodin-loaded PLGA nanoparticle (DGn and EDn) via modified solvent-emulsion-diffusion-evaporation method. Functional stability of prepared nanoparticles and in vitro physiological characterization including mean particle sizes distribution, polydispersity index, surface zeta potential, and morphological examinations were performed. Moreover, drug loading and encapsulation efficiency were also evaluated by measuring drug concentration through spectroscopy and HPLC method. Both drug nanoformulations demonstrated functional drug stability, 200–270 nm sizes with homogeneous particle distribution, negative surface zeta potential stability, and uniform spherical morphology. Moreover, nanoparticles showed in vitro controlled drug release pattern over 24 h with 40–70% of drug depletion. Pharmacokinetics analysis was performed on sixteen rats equally distributed in four groups (DG, ED, DGn, and EDn). Pure drugs and nanoformulations were orally (10 mg/kg) administrated to animal model, and pharmacokinetic profiles of both drugs were evaluated. PLGA nanoparticles were significantly able to alter the pharmacokinetics of DG, while little improvement was observed for ED. Consequently, changes in pharmacokinetics of both drugs are attributed to size and surface characteristics of nanoparticles. DGn and EDn subsidize increased mean plasma residence time and maximize area under curve with decreased drug clearance rate. Resulting in vitro characteristics and in vivo pharmacokinetics data reveal the efficacy of DGn and EDn to be suitable nano-drug delivery modalities with improved bioavailability and pharmacological strength. [ABSTRACT FROM AUTHOR]

Abstract Controlled drug release (CDR) is a significant field of research in medical sciences due to its numerous clinical advantages over traditional methods. Encapsulation of a drug in a polymeric matrix is common technique to achieve CDR. In this study, drug‐polymer particles are prepared using poly(lactic‐co‐glycolic acid) (PLGA) as the polymer and curcumin (CUR) as model drug. Two different methods, electrospray and nanoprecipitation, are used to prepare the particles, and optimal samples in each process are selected based on size and polydispersity index (PDI). Samples are characterized using various tests, and entrapment efficiency (EE%) and drug loading (DL%) are calculated using UV spectroscopy. The results showed that nanoprecipitated and electrosprayed PLGA particles successfully encapsulated CUR, with higher encapsulation efficiency (93.2%) and loading capacity (7.2%) for electrosprayed particles. The in vitro drug release showed that electrospray particles have a slower release rate due to higher encapsulation efficiency. The electrospray method turned out to be more viable for synthesizing these polymer‐drug particles due to smaller particle size, lower PDI, higher entrapment efficiency, and drug loading percentage. Finally, the antibacterial behavior of the particles proved that prepared particles provide excellent antibacterial efficacy (99.9%) and can be used as drug delivery systems.

Celastrol (CST) has positive pharmacological effects on various cancers, but clinical application is limited because of poor water solubility and systemic toxicity. Ferric oxide (Fe3O4) has a large specific surface area and can be functionalized by inorganic modification to form complex magnetic drug delivery systems. Herein, Fe3O4 was surface-modified with citric acid and polyethylene glycol (PEG) (via) the Mitsunobu reaction and then covalently bound to CST. Finally, magnetic microbubbles (MMBs) containing perfluoropropane (C3F8) and Fe3O4-PEG2K-CST particles were constructed with poly(lactic-co-glycolic acid) (PLGA) as the shell membrane. In vitro studies showed that ultrasound-mediated MMBs exhibited improved inhibition of VX2 cell proliferation compared to inhibition achieved using MMBs without ultrasound mediation, blank MMBs, or free CST. In ultrasound mode, MMBs have favorable imaging properties. After the application of a high mechanical index, MMBs collapse through the cavitation effect, releasing their internal Fe3O4-PEG2K-CST. The CST is then delivered to the tumor microenvironment under acidic conditions. In magnetic resonance imaging T2 mode, a specific hypointense signal was observed in the tumor area compared with that before treatment, whereas no significant change occurred in the signal intensity of the surrounding organs. After treatment, pathological examination of tumor-bearing rabbit tissues showed that iron elements accumulated in several apoptosis cells in the tumor area, with no apparent abnormalities found in other areas. Thus, ultrasound-mediated MMBs could significantly improve the drug uptake of solid tumors and inhibit tumor growth with favorable biological safety. [ABSTRACT FROM AUTHOR]

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Neuropathic pain is caused by injury or disease of the somatosensory system, and its course is usually chronic. Several studies have been dedicated to investigating neuropathic pain-related targets; however, little attention has been paid to the persistent alterations that these targets, some of which may be crucial to the pathophysiology of neuropathic pain. The present study aimed to identify potential targets that may play a crucial role in neuropathic pain and validate their long-term impact. Through bioinformatics analysis of RNA sequencing results, we identified Slc9a1 and validated the reduced expression of sodium-hydrogen exchanger 1 (NHE1), the protein that Slc9a1 encodes, in the spinal nerve ligation (SNL) model. Colocalization analysis revealed that NHE1 is primarily co-localized with vesicular glutamate transporter 2-positive neurons. In vitro experiments confirmed that poly(lactic-co-glycolic acid) nanoparticles loaded with siRNA successfully inhibited NHE1 in SH-SY5Y cells, lowered intracellular pH, and increased intracellular calcium concentrations. In vivo experiments showed that sustained suppression of spinal NHE1 expression by siRNA-loaded nanoparticles resulted in delayed hyperalgesia in naïve and SNL model rats, whereas amiloride-induced transient suppression of NHE1 expression yielded no significant changes in pain sensitivity. We identified Slc9a1 , which encodes NHE1, as a key gene in neuropathic pain. Utilizing the sustained release properties of nanoparticles enabled us to elucidate the chronic role of decreased NHE1 expression, establishing its significance in the mechanisms of neuropathic pain. [ABSTRACT FROM AUTHOR]

BACKGROUND: Our group has demonstrated that the immunomodulatory peptide DP7-C has good immunomodulatory functions and can efficiently transfect and deliver miRNAs into cells to exert regulatory functions. OBJECTIVE: To prepare and screen porous poly(lactic-co-glycolic acid) microspheres of different sizes loaded with immunomodulatory peptide miR-26a complexes, construct and optimize the sustained release system, and verify its biocompatibility and osteogenic ability in vivo. METHODS: Microsphere preparation: Porous poly(lactic-co-glycolic acid) microspheres were prepared by double emulsification with NH4HCO3 as the poreforming agent. Three different sizes of porous poly(lactic-co-glycolic acid) microspheres were prepared by adjusting the rotational speed. The microspheres were dispersed in the solution of immunomodulatory peptide DP7-C/miR-26a complex to prepare drug-loaded microspheres. The physical properties of the microspheres were characterized. The best drug-loaded porous poly(lactic-co-glycolic acid) microspheres were selected by comparing productivity, encapsulation rate and release performance for further use. In vitro cell experiment: Drug-loaded and drug-free microsphere solutions with different mass concentrations were co-cultured with rat bone marrow mesenchymal stem cells. CCK-8 assay was performed to verify biocompatibility. Animal in vivo experiment: Nine adult Sprague-Dawley rats were randomly divided into blank group, control group and experimental group, with three rats in each group. Cranial defect models with a diameter of 5 mm were established in all three groups. The rats of the blank group were not implanted with the material. The rats of the control group were implanted with blank microspheres. The rats of the experimental group were implanted with microspheres loaded with DP7-C/miR26a complex. At 8 weeks after operation, the pathological morphology and immunohistochemical staining for alkaline phosphatase of the main organs and skull defects were performed. RESULTS AND CONCLUSION: Microsphere preparation: According to the relevant detection results, the drug-loaded microspheres prepared at 1 000 r/min compared with 500 and 1 200 r/min had uniform size, higher yield and better sustained release performance, which could be used in subsequent experiments. In vitro cell experiment: CCK-8 assay results exhibited that drug-loaded and drug-free microsphere solutions had no effect on the proliferation of bone marrow mesenchymal stem cells and had no obvious cytotoxicity. In vivo experiments: There were no pathological changes in the viscera on hematoxylineosin staining related to the treatment with the intervention. Hematoxylin-eosin staining and Masson staining demonstrated that in the blank group, the defect site was mainly filled by fibrous connective tissue, with a small amount of angiogenesis, but without obvious new bone formation. In the control group, a small amount of new bone formation, fibrous tissue hyperplasia and new capillaries could be visible at the defect site. In the experimental group, there was obvious new bone formation, different degrees of fibrous tissue hyperplasia and new capillaries in the defect area. Immunohistochemical results displayed that alkaline phosphatase was highly expressed in the experimental group compared to the blank group and the control group (P < 0.05). These findings have concluded that the porous poly(lactic-co-glycolic acid)/DP7-C/miR-26a composite system has good biocompatibility and in vivo osteogenic properties and can promote bone regeneration and repair of critical bone defects in the rat skull. [ABSTRACT FROM AUTHOR]

The possibility of improving the biocompatibility of poly(lactic-co-glycolic acid) (PLGA) scaffolds for tissue engineering by their seeding with mesenchymal stem cells (MSCs) is studied. The cell seeding procedure can generally affect the physical and mechanical properties of these scaffolds, which are mainly determined by their architectonics. Three types of PLGA scaffolds were manufactured and studied: (1) monolithic blocks fabricated by injection molding, (2) porous scaffolds formed by supercritical fluid plasticization followed by foaming, and (3) fibrous nonwoven scaffolds fabricated by electrospinning. A quantitative XTT test showed no cytotoxicity for all types of studied scaffolds as well as the higher efficiency of the dynamic seeding method in comparison with the static method. Also, already after 48 h of incubation of the scaffolds with cells, their physical and mechanical properties changed both at the macro and at the micro level. It is assumed that these changes are determined by the processes of aqueous and enzymatic hydrolysis of poly(lactic-co-glycolic acid)s while adhered MSCs altered internal scaffold structure and surface morphology of scaffold surface. Similar transformations of some physicochemical and structural properties of the scaffolds based on other biodegradable polymers or their seeding can also occur as a result of their seeding with various cell cultures, which should indeed be taken into account when applying them for development of tissue engineering constructions. [ABSTRACT FROM AUTHOR]

Tania Mariastella Caputo,1,&ast; Angela Maria Cusano,2,&ast; Sofia Principe,1 Paola Cicatiello,1 Giorgia Celetti,1 Anna Aliberti,1 Alberto Micco,2 Menotti Ruvo,3 Maria Tagliamonte,4 Concetta Ragone,4 Michele Minopoli,5 Maria Vincenza Carriero,5 Luigi Buonaguro,4 Andrea Cusano1,2 1Optoelectronics Group, Department of Engineering, University of Sannio, Palazzo Dell’ Aquila Bosco Lucarelli, Benevento, Italy; 2CeRICTscrl Regional Center Information Communication Technology, Palazzo Ex Poste, Benevento, Italy; 3Institute of Biostructure and Bioimaging, National Research Council, Naples, Italy; 4Innovative Immunological Models Unit, Istituto Nazionale Tumori - IRCCS - “Fond G. Pascale”, Naples, Italy; 5Neoplastic Progression Unit, Istituto Nazionale Tumori IRCCS “Fondazione G. Pascale”, Naples, Italy&ast;These authors contributed equally to this workCorrespondence: Andrea Cusano; Anna Aliberti, Palazzo Dell’Aquila Bosco Lucarelli, Corso Garibaldi 107, Benevento, I-82100, Italy, Email a.cusano@unisannio.it; anna.aliberti@unisannio.itIntroduction: 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.Methods: 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.Results: 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.Conclusion: 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.Graphical Abstract: Keywords: poly(lactic-co-glycolic acid), sorafenib, emulsion solvent evaporation technique, hepatocellular carcinoma, optical fiber, microfluidics

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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. [ABSTRACT FROM AUTHOR]

Glioblastoma (GBM) represents almost half of primary brain tumors, and its standard treatment with the alkylating agent temozolomide (TMZ) is not curative. Treatment failure is partially related to intrinsic resistance mechanisms mediated by the O6-methylguanine-DNA methyltransferase (MGMT) protein, frequently overexpressed in GBM patients. Clinical trials have shown that the anticancer agent bortezomib (BTZ) can increase TMZ's therapeutic efficacy in GBM patients by downregulating MGMT expression. However, the clinical application of this therapeutic strategy has been stalled due to the high toxicity of the combined therapy. The co-delivery of TMZ and BTZ through nanoparticles (NPs) of poly-(lactic-co-glycolic acid) (PLGA) is proposed in this work, aiming to explore their synergistic effect while decreasing the drug's toxicity. The developed NPs were optimized by central composite design (CCD), then further conjugated with transferrin (Tf) to enhance their GBM targeting ability by targeting the blood–brain barrier (BBB) and the cancer cells. The obtained NPs exhibited suitable GBM cell delivery features (sizes lower than 200 nm, low polydispersity, and negative surface charge) and a controlled and sustained release for 20 days. The uptake and antiproliferative effect of the developed NPs were evaluated in in vitro human GBM models. The obtained results disclosed that the NPs are rapidly taken up by the GBM cells, promoting synergistic drug effects in inhibiting tumor cell survival and proliferation. This cytotoxicity was associated with significant cellular morphological changes. Additionally, the biocompatibility of unloaded NPs was evaluated in healthy brain cells, demonstrating the safety of the nanocarrier. These findings prove that co-delivery of BTZ and TMZ in Tf-conjugated PLGA NPs is a promising approach to treat GBM, overcoming the limitations of current therapeutic strategies, such as drug resistance and increased side effects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Non-invasive treatment of spinal cord injury needs to be developed urgently. Nanomaterials have obvious advantages, which can deliver drugs and improve the therapeutic effect. OBJECTIVE: To fabricate sustained-release nanospheres containing neurotrophin-3 and ganglioside GD1a by poly(lactic-co-glycolic acid) and investigate their effects on the repair of spinal cord injury in rats. METHODS: Poly(lactic-co-glycolic acid) nanospheres encapsulated with neurotrophin-3 and ganglioside GD1a were prepared using oil-water emulsion volatile organic solvent method. The sustained release properties of microspheres were tested. Sixty female adult SD rats were randomly divided into five groups with 12 rats in each group. In the sham operation group, the lamina was opened and sutured directly. In the spinal cord injury group, a spinal cord T9 impingement injury model was established. In the neurotrophin group, the nanosphere suspension of slow-release neurotrophin-3 was injected into the injured area of spinal cord T9. In the ganglioside GD1a group, the sustained-release ganglioside GD1a nanosphere suspension was injected into the spinal cord T9 injury area. The experimental group was injected with nanosphere suspension of sustained-release neurotrophin-3 and ganglioside GD1a in the injured area of spinal cord T9. Open field test and BBB scoring were conducted weekly after operation. The sections were taken 4 and 8 weeks after surgery for morphological observation. RESULTS AND CONCLUSION: (1) After soaking in PBS for 14 days in vitro, the sustained-release nanospheres could continuously release neurotrophin-3 and ganglioside GD1a. (2) At 7 and 8 weeks after surgery, compared with the spinal cord injury group, the BBB score and the total open field distance of the rats increased in the neurotrophin group and the experimental group (P < 0.05). The results of Nissl staining showed that at 4 and 8 weeks after surgery, the number of motor neurons increased in the anterior horn of caudal gray matter in the experimental group compared with the spinal cord injury group (P < 0.05). At 8 weeks after surgery, the number of motor neurons increased in the anterior horn of caudal gray matter in the neurotrophin group compared with the spinal cord injury group (P < 0.05). The results of immunofluorescence staining showed that compared with the spinal cord injury group, the neurotrophin group at 8 weeks and the experimental group at 4 and 8 weeks had increased spinal white matter ventral nerve fibers (P < 0.05); the expression of myelin basic protein on the ventral side of the spinal cord white matter increased at 4 and 8 weeks in the ganglioside GD1a and experimental groups (P < 0.05); the expression of myelin basic protein in the neurotrophin group increased at 8 weeks after operation (P < 0.05); the descending propriospinal tract increased in the neurotrophin group and the experimental group at 8 weeks (P < 0.05). (3) The results showed that neurotrophin-3 microspheres alone or in combination with ganglioside GD1a microspheres could promote the survival of motor neurons and nerve fibers around the spinal cord injury site and improve the motor function of the hind limbs of rats. [ABSTRACT FROM AUTHOR]

[Display omitted] 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. [ABSTRACT FROM AUTHOR]

This paper outlines the methodology and results for a two-species finite volume scalar computational drug transport model developed for simulating the mass transport of Poly(lactic-co-glycolic acid (PLGA)) from a half-embedded single strut implanted in a coronary arterial vessel wall. The mathematical drug transport model incorporates the convection-diffusion equation in scalar form (dimensionless) with a two-species (free-drug and bound-drug) mass transport setup, including reversible equilibrium reaction source terms for the free and bound-drug states to account for the pharmaco-kinetic reactions in the arterial wall. The relative reaction rates of the added source terms control the interconversion of the drug between the free and bound-drug states. The model is solved by a 2D finite-volume method for discretizing and solving the free and bound drug transport equations with anisotropic vascular drug diffusivities. This model is an improvement over previously developed models using the finite-difference and finite element method. A dimensionless characteristic scaling pre-analysis was conducted a priori to evaluate the significance of implementing the reaction source terms in the transport equations. This paper reports the findings of an investigation of the interstitial flow profile into the arterial wall and the free and bound drug diffusion profiles with a parametric study of varying the polymer drug concentration (low and high), tortuosity, porosity, and Peclet and DamKöhler numbers over the course of 400 h (16.67 days). The results also reveal how a single species drug delivery model that neglects both a reversible binding reaction source term and the porosity and tortuosity of the arterial wall cannot accurately predict the distribution of both the free and bound drug. [ABSTRACT FROM AUTHOR]

Microspheres play an important role in controlling drug delivery and release rate accurately. To realize the sustainable release of insoluble small-molecule drugs, a new three-phase flow-focusing microfluidic device was developed to produce the drug-loaded sustained-release microspheres which were prepared with bicalutamide (BCS class-II) as the model drug and poly(lactide-co-glycolide) (PLGA) as the carrier material. Under optimized prescription conditions, the microspheres showed a smooth surface and uniform size of 51.33 μm with a CV value of 4.43%. Sustained-release microspheres had a releasing duration of around 40 days in vitro without any initial burst release. The drug release mechanism of the microspheres was drug diffusion and polymer erosion. Meanwhile, the drug release of microspheres in vivo could be up to 30 days. Briefly, the microfluidic device in this study provides a new solution for the preparation of sustained-release microspheres for insoluble small-molecule drugs. PLGA sustained-release microspheres developed by the microfluidic device have good application prospects in precise delivery and sustainable release of insoluble small-molecule drugs.

The updating and optimization of drug delivery systems is critical for better in vivo behaviors of drugs, as well as for improving impaired implant osseointegration in diabetes. Numerous studies have reported the benefits of exendin-4 on diabetic bone, with the potential to enhance osseointegration in diabetes. To construct an appropriate sustained-release system of exendin-4 targeting implant osseointegration in diabetes, this study fabricated exendin-4-loaded microspheres using poly(lactic-co-glycolic acid) (PLGA) and chitosan. The morphology, size, encapsulation efficiency, and drug release behavior of microspheres were investigated. The bioactivity of drug-loaded microspheres on cell proliferation and osteogenic differentiation of diabetic BMSCs was investigated to examine the pharmacologic action of exendin-4 loaded into chitosan–PLGA microspheres. Further, the influence of microspheres on osseointegration was evaluated using type 2 diabetes mellitus (T2DM) rat implant model. After 4 weeks, the samples were evaluated by radiological and histological analysis. The results of in vitro experiments showed that the prepared exendin-4-loaded chitosan–PLGA microspheres have good properties as a drug delivery system, and the chitosan could improve the encapsulation efficiency and drug release of PLGA microspheres. In addition, exendin-4-loaded microspheres could enhance the proliferation and osteogenic differentiation of diabetic BMSCs. The results of in vivo experiments showed the exendin-4-loaded microspheres significantly improved the impaired osseointegration and bone formation around implants in T2DM rats without affecting blood glucose levels. Thus, the local application of exendin-4-loaded chitosan–PLGA microspheres might be a promising therapeutic strategy for improving the efficacy of dental implants in T2DM individuals.

Biocompatible and biodegradable polymers such as poly(lactic-co-glycolic acid), PLGA and polycaprolactone, PCL nanoparticles (NPs) have been used successfully as drug carriers in controlled drug release. The main weakness is the generally low drug loading (1–-5%) of the NPs. An option to enhance the drug content of NPs is to find the optimum matrix for a given drug molecule. To reveal the influence of matrix and drug polarity on the favoured encapsulation, polymeric NPs loaded with a series of alkyl-4-hydroxybenzoate (paraben) with increasing alkyl chain length (C1-C8) as model drugs were prepared by nanoprecipitation method. The paraben series represents the drugs with various polarities while the selected matrix polymers show increased hydrophobicity: PLGA with 50% lactic acid content (PLGA50) < PLGA with 75% lactic acid content (PLGA75) < PCL. The drug content of the PLGA NPs was found to significantly increase up to 10% with the hydrophobicity of the parabens, while encapsulation was further boosted by applying PCL. To find the proper fit between drug and matrix and finely tune the polarity of the NPs, as a novel approach, blends of PLGA50 and PCL were applied as matrix polymers. The drug loading of the NPs was proved to be dependent on the systematically changed blend composition. Furthermore, the introduction of PCL into the PLGA50 matrix improves the release kinetics of the active component.

Biofragmentable anastomosis ring (BAR) is an ideal sutureless alternative for intestinal connection that is frequently demanded in colonic surgery. However, it is challenging to insert a bulky BAR into the soft and slippery intestine. Here 4D printing of an anastomosis ring with shape memory capability is presented via fused deposition modeling (FDM) 3D printing. The shape memory anastomosis ring can recover from a compressed shape that facilitates the insertion to the permanent shape for connection and supporting. Degradation kinetics is tuned by controlling the blending composition of polylactic acid and poly(lactic‐co‐glycolic acid), so that the device can be excreted after the intestine healing. The shape recovery temperature is adjusted to 50 °C that the human body can withstand for a while. Grid structure and hook lock are designed and printed to guarantee dimension reduction upon programming and stable connection after shape recovery, respectively. A conceptual anastomotic operation shows the advantages and prospects of shape transformation. The 4D printing strategy may promote intestinal anastomosis development and inspire more opportunities for minimally invasive medical surgery. [ABSTRACT FROM AUTHOR]

[Display omitted] In the present study, a comprehensive polymer degradation-drug diffusion model is developed to describe the polymer degradation kinetics and quantify the release rate of an active pharmaceutical ingredient (API) from a size-distributed population of drug-loaded poly(lactic- co -glycolic) acid (PLGA) carriers in terms of material and morphological properties of the drug carriers. To take into account the spatial–temporal variation of the drug and water diffusion coefficients, three new correlations are developed in terms of spatial–temporal variation of the molecular weight of the degrading polymer chains. The first one relates the diffusion coefficients with the time-spatial variation of the molecular weight of PLGA and initial drug loading and, the second one with the initial particle size, and the third one with evolution of the particle porosity due to polymer degradation. The derived model, comprising a system of partial differential and algebraic equations, is numerically solved using the method of lines and validated against published experimental data on the drug release rate from a size distributed population of piroxicam-PLGA microspheres. Finally, a multi-parametric optimization problem is formulated to calculate the optimal particle size and drug loading distributions of drug-loaded PLGA carriers to realize a desired zero-order drug release rate of a therapeutic drug over a specified administration period of several weeks. It is envisaged that the proposed model-based optimization approach will aid the optimal design of new controlled drug delivery systems and, consequently, the therapeutic outcome of an administered drug. [ABSTRACT FROM AUTHOR]

Tissue-engineering technologies have the potential to provide an effective approach to bone regeneration. Based on the published literature and data from our laboratory, two biomaterial inks containing PLGA and blended with graphene nanoparticles were fabricated. The biomaterial inks consisted of two forms of commercially available PLGA with varying ratios of LA:GA (65:35 and 75:25) and molecular weights of 30,000–107,000. Each of these forms of PLGA was blended with a form containing a 50:50 ratio of LA:GA, resulting in ratios of 50:65 and 50:75, which were subsequently mixed with a 0.05 wt% low-oxygen-functionalized derivative of graphene. Scanning electron microscopy showed interconnected pores in the lattice structures of each scaffold. The cytocompatibility of human ADMSCs transduced with a red fluorescent protein (RFP) was evaluated in vitro. The in vivo biocompatibility and the potential to repair bones were evaluated in a critically sized 5 mm mechanical load-bearing segmental femur defect model in rats. Bone repair was monitored by radiological, histological, and microcomputed tomography methods. The results showed that all of the constructs were biocompatible and did not exhibit any adverse effects. The constructs containing PLGA (50:75)/graphene alone and with hADMSCs demonstrated a significant increase in mineralized tissues within 60 days post-treatment. The percentage of bone volume to total volume from microCT analyses in the rats treated with the PLGA + cells construct showed a 50% new tissue formation, which matched that of a phantom. The microCT results were supported by Von Kossa staining. [ABSTRACT FROM AUTHOR]

Various poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with the ginger fraction were fabricated by controlling the electrospray parameters and their biocompatibility and antibacterial activity were identified in this study. The morphology of the microspheres was observed using scanning electron microscopy. The core-shell structures of the microparticles and the presence of ginger fraction in the microspheres were confirmed by fluorescence analysis using a confocal laser scanning microscopy system. In addition, the biocompatibility and antibacterial activity of PLGA microspheres loaded with ginger fraction were evaluated through a cytotoxicity test using osteoblast MC3T3-E1 cells and an antibacterial test using Streptococcus mutans and Streptococcus sanguinis, respectively. The optimum PLGA microspheres loaded with ginger fraction were fabricated under electrospray operational conditions with 3% PLGA concentration in solution, an applied voltage of 15.5 kV, a flow rate of 15 µL/min in the shell nozzle, and 3 µL/min in the core nozzle. The effectual antibacterial effect and enhanced biocompatibility were identified when a 3% ginger fraction in PLGA microspheres was loaded. [ABSTRACT FROM AUTHOR]

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.

IntroductionTarsal 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.MethodsThree 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.ResultsWe 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.ConclusionThe 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.

Collagen, with low antigenicity and excellent cell adhesion, is a biomaterial mainly used for regenerating bone, cartilage, and skin, owing to its biocompatibility and biodegradability. Results from a previous study confirmed that a scaffold mixed with duck feet-derived collagen (DC) and Poly(lactic- co -glycolic acid) (PLGA) reduced inflammatory reaction and increased bone regeneration. To develop an optimal bone substitute we included hydroxyapatite (HAp), a key osteoconductive material, in a DC and PLGA mixture. We fabricated 0, 10, 20, 40, 60, and 80 wt% DC/PLGA/HAp scaffolds and studied their potential for bone tissue engineering. Characteristic analysis of the scaffold and seeding of rabbit bone marrow mesenchymal stem cells (rBMSCs) on the scaffold were conducted to investigate cell proliferation, osteogenic differentiation, and bone formation. We confirmed that increasing DC concentration not only improved the compressive strength of the DC/PLGA/HAp scaffold but also cell proliferation and osteogenic differentiation. It was found through comparison with previous studies that including HAp in the scaffold also promotes osteogenic differentiation. Our study thus shows through in vivo results that the 80 wt% DC/PLGA/HAp scaffold promotes bone mineralization and collagen deposition while reducing the inflammatory response. Hence, 80 wt% DC/PLGA/HAp has excellent potential as a biomaterial for bone regeneration applications. [ABSTRACT FROM AUTHOR]

Some cancer cells rely heavily on non-essential biomolecules for survival, growth, and proliferation. Enzyme based therapeutics can eliminate these biomolecules, thus specifically targeting neoplastic cells; however, enzyme therapeutics are susceptible to immune clearance, exhibit short half-lives, and require frequent administration. Encapsulation of therapeutic cargo within biocompatible and biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) is a strategy for controlled release. Unfortunately, PLGA NPs exhibit burst release of cargo shortly after delivery or upon introduction to aqueous environments where they decompose via hydrolysis. Here, we show the generation of hybrid silica-coated PLGA (SiLGA) NPs as viable drug delivery vehicles exhibiting sub-200 nm diameters, a metastable Zeta potential, and high loading efficiency and content. Compared to uncoated PLGA NPs, SiLGA NPs offer greater retention of enzymatic activity and slow the burst release of cargo. Thus, SiLGA encapsulation of therapeutic enzymes, such as asparaginase, could reduce frequency of administration, increase half-life, and improve efficacy for patients with a range of diseases. [ABSTRACT FROM AUTHOR]

Modern medical science believes that astragalus polysaccharides (APS) have the efficacy of strengthening immune system, while their peculiarities greatly reduced clinical applications. Poly(lactic- co -glycolic acid) (PLGA) is a synthetic carrier material with outstanding biochemical properties. In this study, PLGA materials were used to prepare the novel pH-responsive targeting drug delivery carriers which were encapsulated APS inside. The OVA-loaded pH-responsive APS-encapsulated PLGA Nanoparticles (OVA-loaded pH-responsive APSPs) and the OVA-loaded APSPs were constructed by multiple emulsion solvent evaporation method. Characterization and immunoenhancing activities of PLGA nanoparticles (NPs) were evaluated in vitro and in vivo. The size of NPs ranged from 142.6 to 194.6 nm, and all NPs were negatively charged. Additionally, pH-responsive APSPs shown violent release behaviors in an acidic environment. pH-responsive APSPs had low cytotoxicity, and significantly enhanced expression of MHC-II, CD80, CD86, and phagocytosis ability of macrophages. Both OVA-loaded NPs could stimulate greater Th1-biased immune responses compared with APS alone, and they could significantly promote proliferation, differentiation, and maturity of splenic lymphocytes and dendritic cells in mice respectively. NPs induced significantly greater antigen-specific IgG antibody responses and expression of IL-4, IL-6, IFN-γ, and TNF-α. Moreover, OVA-loaded pH-responsive APSPs had an aptitude for both cellular and humoral immunity reinforcement during early immunization, while OVA-loaded APSPs had advantages on later stages of immune responses. [Display omitted] [ABSTRACT FROM AUTHOR]

Nonunion bone fractures can impact the quality of life and represent a major economic burden. Scaffold-based tissue engineering has shown promise as an alternative to bone grafting. Achieving desirable bone reconstruction requires appropriate surface properties, together with optimizing the internal architecture of 3D scaffolds. This study presents the surface modification of poly(lactic-co-glycolic acid) (PLGA), collagen, and PLGA-collagen via an argon plasma treatment. Argon plasma can modify the surface chemistry and topography of biomaterials and improve in vivo integration. Solvent-cast films were prepared using 1,1,1,3,3,3-hexafluoro-2-propanol and characterized via differential scanning calorimetry, thermogravimetric analysis, contact angle measurement, and critical surface tension analysis. For PLGA films, the water contact angle dropped from 70° to 42°, whereas the diiodomethane contact angle reduced from 53° to 32° after the plasma treatment. A set of PLGA-collagen formulations were loaded with nanohydroxyapatite (nHA) and polyethylene glycol (PEG) to enhance their osteoconductivity and hydrophilicity. Then, 3D scaffolds were fabricated using a 3D Bioplotter and characterized via Fourier-transform infrared (FTIR) spectroscopy. A bicinchoninic acid assay (BCA) was used to compare the protein release from the untreated and plasma-treated scaffolds into phosphate-buffered saline (PBS). The plasma-treated scaffolds had a lower protein release, and the difference compared to the untreated scaffolds was statistically significant. [ABSTRACT FROM AUTHOR]

The pH inside the aqueous pores of poly(lactic- co -glycolic acid) (PLGA) microspheres, often termed microclimate pH (μ pH), has been widely evaluated in vitro and shown to commonly be deleterious to pH-labile encapsulated drug molecules. However, whether the in vitro μ pH is representative of the actual in vivo values has long been remained a largely unresolved issue. Herein we quantitatively mapped, for the first time, the in vivo μ pH distribution kinetics inside degrading PLGA microspheres by combining two previously validated techniques, a cage implant system and confocal laser scanning microscopy. PLGA (50/50, Mw = 24–38 kDa, acid-end capped and ester-capped) microsphere formulations with and without encapsulating exenatide, a pH-labile peptide that is known to be unstable when pH > 4.5, were administered to rats subcutaneously via cage implants for up to 6 weeks. The results were compared with two different in vitro conditions. Strikingly, the in vivo μ pH developed similarly to the low microsphere concentration in vitro condition with 1- μ m nylon bags but very different from conventional high microsphere concentration sample-and-separate conditions. Improved maintenance of stable external pH in the release media for the former condition may have been one important factor. Stability of exenatide remaining inside microspheres was evaluated by mass spectrometry and found that it was steadily degraded primarily via pH-dependent acylation with a trend that slightly paralleled the changes in μ pH. This methodology may be useful to elucidate pH-triggered instability of PLGA encapsulated drugs in vivo and for improving in vivo -predictive in vitro conditions for assessing general PLGA microsphere performance. [Display omitted] [ABSTRACT FROM AUTHOR]

Recent advances in understanding Alzheimer's disease (AD) suggest the possibility of an infectious etiology, with Porphyromonas gingivalis emerging as a prime suspect in contributing to AD. P. gingivalis may invade systemic circulation via weakened oral/intestinal barriers and then cross the blood-brain barrier (BBB), reaching the brain and precipitating AD pathology. Based on the proposed links between P. gingivalis and AD, a prospective approach is the development of an oral nanovaccine containing P. gingivalis antigens for mucosal delivery. Targeting the gut-associated lymphoid tissue (GALT), the nanovaccine may elicit both mucosal and systemic immunity, thereby hampering P. gingivalis ability to breach the oral/intestinal barriers and the BBB, respectively. The present study describes the optimization, characterization, and in vitro evaluation of a candidate chitosan-coated poly(lactic-co-glycolic acid) (PLGA-CS) nanovaccine containing a P. gingivalis antigen extract. The nanocarrier was prepared using the double emulsion solvent evaporation method and optimized for selected experimental factors, e.g. PLGA amount, surfactant concentration, w 1 /o phase ratio, applying a d-optimal statistical design to target the desired physicochemical criteria for its intended application. After nanocarrier optimization, the nanovaccine was characterized in terms of particle size, polydispersity index (PdI), ζ-potential, encapsulation efficiency (EE), drug loading (DL), morphology, and in vitro release profile, as well as for mucoadhesivity, stability under simulated gastrointestinal conditions, antigen integrity, in vitro cytotoxicity and uptake using THP-1 macrophages. The candidate PLGA-CS nanovaccine demonstrated appropriate physicochemical, mucoadhesive, and antigen release properties for oral delivery, along with acceptable levels of EE (55.3 ± 3.5 %) and DL (1.84 ± 0.12 %). The integrity of the encapsulated antigens remained uncompromised throughout NPs production and simulated gastrointestinal exposure, as confirmed by SDS-PAGE and Western blotting analyses. Furthermore, the nanovaccine showed effective in vitro uptake, while exhibiting low cytotoxicity. Taken together, these findings underscore the potential of PLGA-CS NPs as carriers for adequate antigen mucosal delivery, paving the way for further investigations into their applicability as vaccine candidates against P. gingivalis. [Display omitted] [ABSTRACT FROM AUTHOR]

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.