Effects of rAmb a 1-Loaded PLGA-PEG Nanoparticles in a Murine Model of Allergic Conjunctivitis.

Ambrosia artemisiifolia (Amb a) contains many allergens. Allergic conjunctivitis caused by Ambrosia artemisiifolia and its related allergen-specific immunotherapy (AIT) are seldom studied at present. poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) is a very good nano-carrier, which has been applied in the medical field. In this context, we studied the immunotherapy effect and potential mechanism of recombinant Amb a 1 (rAmb a 1)-loaded PLGA-PEG nanoparticles. A mouse allergic conjunctivitis model was established with Ambrosia artemisiifolia crude extract, and the nanoparticles were used for AIT through direct observation of conjunctival tissue, degranulation of mast cells in conjunctival tissue, serum-specific antibodies, cytokines and other assessment models. The treatment of nanoparticles enhanced the secretion of T-helper 1 (Th1) cytokine Interferon-gama (IFN-γ) and the production of immunoglobulin G (IgG)2a (IgG2a), inhibited the secretion of T-helper 2 (Th2) cytokine Interleukin (IL)-13 and IL-4 and the level of IgE. Especially, degranulation of mast cells and expression of mast cell protease-1 (MCP-1) in conjunctival tissue was reduced significantly. In this study, we proved that the nanoparticles prepared by rAmb a 1 and PLGA-PEG have an immunotherapy effect on allergic conjunctivitis in mice.

Therapeutic implications of nano-encapsulated rifabutin, azithromycin & ethambutol against experimental Mycobacterium avium infection in mice.

Background & objectives: Mycobacterium avium causes atypical infection in both immunocompetent and immunocompromised individuals. Conventional chemotherapy for M. avium infection is not efficient due to lengthy course of treatment and drug-associated toxic side effects. The present study was aimed at reducing dosing frequency of antimicrobial regimen consisting of azithromycin (AZM), rifabutin (RBT) and ethambutol (EMB) by encapsulation of drugs in nanoparticles (NPs) in experimental M. avium infection in mice. Methods: Poly (DL-lactide-co-glycolide) NPs containing anti-M. avium drugs were prepared, characterized and studied for their pharmacokinetics and pharmacodynamics parameters. Drug-loaded NPs were further analyzed for their therapeutic efficacy against experimental M. avium infection in mice. Results: Drug-loaded NPs were of size 227.3±16.4 for RBT, 334.35±11.7 for AZM and 509.85±20.5 for EMB with smooth surface morphology and negative zeta potential. AZM, EMB and RBT from NPs were detectable for 6, 4 and 5 days, respectively, in the mice plasma, whereas free drugs were cleared from mice circulation within 24 h. Chemotherapeutic effects of weekly administered drug-loaded NPs were equivalent to daily administered free drugs. Interpretation & conclusions: Our findings showed that NPs gave sustained release of drugs inside plasma and organs, thus decreasing dosage frequency, and their weekly dosage had therapeutic efficacy equivalent to daily dosage of free drugs.

Sustained release of calcium hydroxide from poly(DL-lactide-co-glycolide) acid microspheres for apexification.

Calcium hydroxide (CH) loaded poly(DL-lactide-co-glycolide) acid (PLGA) microspheres (MS) might be used for apexification requiring a sustained release of Ca(2+). The aim of this study was to formulate and characterize CH-PLGA-MS. The CH-loaded MS were prepared by either oil-in-water (O/W) or water-in-oil/in-water (W/O/W) emulsion solvent evaporation technique. MS produced by the O/W technique exhibited a larger diameter (18.63 ± 7.23 µm) than the MS produced by the W/O/W technique (15.25 ± 7.37 µm) (Mann-Whitney U test P < 0.001). The CH encapsulation efficiency (E e) and Ca(2+) release were calculated from data obtained by absorption techniques. Ca(2+) release profile was evaluated for 30 days. To know the E e, the CH-loaded MS were dissolved in 1 M NaOH to release all its content and a Ca(2+) colorimetric marker was added to this solution. The reagent marked the Ca(2+) in blue color, which was then measured by a UV-Vis system (650 nm). The percentage of E e was calculated on the basis of the theoretical loading. The E e of the O/W-produced MS was higher (24 %) than the corresponding percentage of the W/O/W-produced MS (11 %). O/W- and W/O/W-produced MS released slower and lower Ca(2+) than a control CH paste with polyethylene glycol 400 (Kruskal-Wallis test). O/W-produced MS released higher Ca(2+) than W/O/W-produced MS (statistically significant differences; P < 0.05). In conclusion, the CH-PLGA-MS were successfully formulated; the technique of formulation influenced the size, encapsulation efficiency and release profile. The MS were better sustained release system than the CH paste.

Formulation and in vitro characterization of poly(dl-lactide-co-glycolide)/Eudragit RLPO or RS30D nanoparticles as an oral carrier of levofloxacin hemihydrate.

The main objective of this study was to design positively charged Levofloxacin Hemihydrate (Levo-h)-loaded nanoparticles with improved entrapment efficiency and antibacterial activity. PLGA alone or in combinations with Eudragit® RLPO or RS30D with or without positively charged inducing agent; 1,2-dioleoyl-3-trimethylammonium-propane, chloride salt (DOTAP); were used for preparation of nanoparticles. Blending between PLGA and Eudragit® RLPO or RS30D with inclusion of DOTAP caused a marked increase in entrapment efficiency and switched zeta potential from negative to positive. Nanoparticle formulations; NR3 (Levo-h:PLGA:Eudragit® RLPO; 1:1:1 w/w with DOTAP) and NS3 (Levo-h:PLGA:Eudragit® RS30D; 1:1:1 w/w with DOTAP) that possess high positive zeta potential (59.3 ± 7.5 and 55.1 ± 8.2 mV, respectively) and Efficient Levo-h entrapment (89.54 ± 1.5 and 77.65 ± 1.8%, respectively) were selected for further examinations; in vitro release, physical stability and microbiological study. NR3 and NS3 showed significant sustained release of Levo-h. NR3 and NS3 exhibited good stability after storage at room temperature. Microbiological assay showed strengthened antibacterial activity of NR3 against both types of gram-negative bacteria (E. coli, Ps. aeruginosa) and of NS3 against Ps. aeruginosa compared to free Levo-h solution. NR3 and NS3 appear to be promising oral delivery system for Levo-h.

Preliminary investigation on the design of biodegradable microparticles for ivermectin delivery: set up of formulation parameters.

The aim was to design sterile biodegradable microparticulate drug delivery systems based on poly(dl-lactide) (PLA) and poly(ε-caprolactone) (PCL) and containing ivermectin (IVM), an antiparasitic drug, for subcutaneous administration in dogs. The drug delivery system should: (i) ensure a full 12-month protection upon single dose administration; (ii) be safe with particular attention regarding IVM dosage and its release, in order to prevent over dosage side effects. This preliminary work involves: polymer selection, evaluation of the effects of γ-irradiation on the polymers and IVM, investigation and set up of suitable microparticle preparation process and parameters, IVM-loaded microparticles in vitro release evaluation. Results of gel permeation chromatography analysis on the irradiated polymers and IVM mixtures showed that combination of IVM with the antioxidant α-tocopherol (TCP) reduces the damage extent induced by irradiation treatment, independently on the polymer type. Solvent evaporation process was successfully used for the preparation of PLA microparticles and appropriately modified; it was recognized as suitable for the preparation of PCL microparticles. Good process yields were achieved ranging from 76.08% to 94.72%; encapsulation efficiency was between 85.76% and 91.25%, independently from the polymer used. The type of polymer and the consequent preparation process parameters affected microparticle size that was bigger for PCL microparticles (480-800 µm) and solvent residual that was >500 ppm for PLA microparticles. In vitro release test showed significantly faster IVM release rates from PCL microparticles, with respect to PLA microparticles, suggesting that a combination of the polymers could be used to obtain the suitable drug release rate.

PLGA-nanoparticle mediated delivery of anti-OX40 monoclonal antibody enhances anti-tumor cytotoxic T cell responses.

OX40 (CD134) is a tumor necrosis factor (TNF) receptor expressed mainly on activated T cells and transmits a potent costimulatory signal once engaged. Agonistic anti-OX40 monoclonal antibody (mAb) enhances tumor immune response leading to therapeutic effects in mouse tumor models. However, when tested in phase I clinical trials it did not show objective clinical activity in cancer patients. In this study, we examined the feasibility of nanoparticle (NP)-mediated delivery of anti-OX40 mAb to efficiently induce cytotoxic T lymphocyte (CTL) responses. The biodegradable poly(DL-lactide-co-glycolide) nanoparticle (PLGA-NP) carrying anti-OX40 mAb, anti-OX40-PLGA-NP, was prepared by double emulsion method and showed an average diameter of 86 nm with a loading efficiency of 25%. We found that anti-OX40-PLGA-NP induced CTL proliferation and tumor antigen-specific cytotoxicity as well as cytokine production more strongly than free anti-OX40 mAb. These results suggest that PLGA-based nanoparticle formulation may provide efficient delivery system of anti-OX40 mAb for cancer immunotherapy.

Poly(dl-lactide) Polymer Blended with Mineral Phases for Extrusion 3D Printing-Studies on Degradation and Biocompatibility.

A promising therapeutic option for the treatment of critical-size mandibular defects is the implantation of biodegradable, porous structures that are produced patient-specifically by using additive manufacturing techniques. In this work, degradable poly(DL-lactide) polymer (PDLLA) was blended with different mineral phases with the aim of buffering its acidic degradation products, which can cause inflammation and stimulate bone regeneration. Microparticles of CaCO3, SrCO3, tricalcium phosphates (α-TCP, ß-TCP), or strontium-modified hydroxyapatite (SrHAp) were mixed with the polymer powder following processing the blends into scaffolds with the Arburg Plastic Freeforming 3D-printing method. An in vitro degradation study over 24 weeks revealed a buffer effect for all mineral phases, with the buffering capacity of CaCO3 and SrCO3 being the highest. Analysis of conductivity, swelling, microstructure, viscosity, and glass transition temperature evidenced that the mineral phases influence the degradation behavior of the scaffolds. Cytocompatibility of all polymer blends was proven in cell experiments with SaOS-2 cells. Patient-specific implants consisting of PDLLA + CaCO3, which were tested in a pilot in vivo study in a segmental mandibular defect in minipigs, exhibited strong swelling. Based on these results, an in vitro swelling prediction model was developed that simulates the conditions of anisotropic swelling after implantation.

Synthesis and Characterization of Poly(DL-lactide) Containing Fluorene Structures.

9,9-bis[4-(2-hydroxy-3-acryloyloxypropoxy)phenyl]fluorene (BPF) hydroxyl groups (-OH) were used as initiators in the ring-opening polymerization reaction with DL-lactide monomers at different molar ratios to synthesize a Poly(DL-lactide) polymer containing bisphenol fluorene structure and acrylate functional groups (DL-BPF). The polymer's structure and molecular weight range were analyzed using NMR (1H, 13C) and gel permeation chromatography. DL-BPF was then subjected to photocrosslinking using the photoinitiator Omnirad 1173, resulting in the formation of an optically transparent crosslinked polymer. Characterization of the crosslinked polymer involved analyzing its gel content, refractive index, thermal stability (via differential scanning thermometry (DSC) and thermogravimetric analysis (TGA)), as well as conducting cytotoxicity tests. The crosslinked copolymer exhibited a maximum refractive index of 1.5276, a maximum glass transition temperature of 61.1 °C, and cell survival rates higher than 83% in the cytotoxicity tests.

Intracellular Activity of Poly (DL-Lactide-co-Glycolide) Nanoparticles Encapsulated with Prothionamide, Pyrazinamide, Levofloxacin, Linezolid, or Ethambutol on Multidrug-Resistant Mycobacterium tuberculosis.

BACKGROUND: Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is a major cause of death amongst tuberculosis patients. Nanomedicine avoids some limitations of conventional drug treatment and increases therapeutic efficacy against bacterial infections. However, the effect of anti-TB drug nanoparticle (NP) compounds in anti-TB regimens against MDR-TB remains unclear. OBJECTIVE: The objective of this article is to prepare levofloxacin, linezolid, ethambutol, prothionamide, and pyrazinamide encapsulated NPs and to evaluate their therapeutic efficacy against MDR-TB in macrophages. METHODS: Drug-loaded PLGA NPs were prepared by the multiple emulsion method. The colocalization, intracellular release, and anti-TB activity of these NPs were investigated on cultured macrophages. The immune phenotype of the macrophages, including their mitochondrial membrane potential, reactive oxygen species (ROS), and nitric oxide (NO) production, was evaluated following treatment with NPs or free drug compounds. RESULTS: All drug-loaded PLGA NPs were spherical in shape, 150 to 210 nm in size, and showed 14.22% to 43.51% encapsulation efficiencies and long-duration release. Drug-loaded PLGA NPs were mainly distributed in the cytoplasm of macrophages, showed high cellular compatibility, and maintained their concentration for at least 13 days. Compared with the free drug compounds, the number of colonies after exposure to PLGA NP compounds was significantly less. The enhanced antibacterial activity of the NP compounds may be due to the enhanced levels of ROS and NO and the increased early apoptosis stress within M. tuberculosis-infected macrophages additionally. CONCLUSION: The application of PLGA NP compounds not only enhances drug efficacy but also induces innate bactericidal events in macrophages, confirming this as a promising approach for MDR-TB therapy.

Effects of Chemical Composition on the Shape Memory Property of Poly(dl-lactide-co-trimethylene carbonate) as Self-Morphing Small-Diameter Vascular Scaffolds.

Smart materials have great potential in many biomedical applications, in which biodegradable shape memory polymers (SMPs) can be used as surgical sutures, implants, and stents. Poly(dl-lactide-co-trimethylene carbonate) (PDLLTC) represents one of the promising SMPs and is widely used in biomedical applications. However, the relationship between its shape memory property and chemical structure has not been fully studied and needs further elaboration. In this work, PDLLTC copolymers in different compositions have been synthesized, and their shape memory properties have been investigated. It has been found that the shape memory property is related to the chemical composition and polymeric chain segments. The copolymer with a DLLA/TMC ratio of 75:25 (PDLLTC7525) has been demonstrated with great shape fixation and recovery ratio at human body temperature. Furthermore, PDLLTC7525-based self-morphing small-diameter vascular scaffolds adhered with inner electrospun aligned gelatin/hyaluronic acid (Gel/HA) nanofibers have been constructed, as a merit of its shape memory property. The scaffolds have been demonstrated to facilitate the proliferation and adhesion of endothelial cells on the inner layer. Therefore, PDLLTC with tailorable shape memory properties represents a promising candidate for the development of SMPs, as well as for small-diameter vascular scaffolds construction.

Chitosan-coated PLGA nanoparticles for transcutaneous immunization: Skin distribution in lysozyme-sensitized mice.

The effect of transcutaneous immunization was studied using a combined system of poly(DL-lactide-co-glycolide) (PLGA) nanoparticles and iontophoresis (IP). Both hen egg-white lysozyme (HEL)-loaded PLGA nanoparticles coated with chitosan hydroxypropyltrimonium chloride and their fluorescent nanoparticles were prepared using an antisolvent diffusion method. Their mean volume diameters were 87.6 ± 38.9 nm and 84.9 ± 27.6 nm, respectively. It was suggested from the results of the ex vivo skin accumulation study using fluorescent nanoparticles that the HEL released from the nanoparticles to the skin surface was efficiently delivered to antigen-presenting cells. HEL-specific IgG1 and IgG2a titers were determined in an in vivo percutaneous immunoreactivity study using lysozyme-sensitized mice. As results, the group using nanoparticles and IP showed 1.33 times higher HEL-specific IgG1 titer than a sham treatment group. The HEL-specific IgG2a titer was 1.36 times higher in the nanoparticles and IP group than in the HEL solution and IP group. It was suggested from the quantification results of total IgE in serum that the combined use of PLGA nanoparticles and IP reduced the total IgE concentration. The level of cytokines may have decreased due to Th1 cell activation and relative suppression of Th2 cells. The cytokine level is presumed to be reduced by activation of Th1 cells and relative suppression of Th2 cells. The histamine amount in plasma and rectal temperature after the induction of anaphylactic shock using lysozyme-sensitized mice were also studied, which indicates that the combined use of PLGA nanoparticles and IP may provide the same therapeutic effect as an injection.

Polymers Based on PLA from Synthesis Using D,L-Lactic Acid (or Racemic Lactide) and Some Biomedical Applications: A Short Review.

Poly(lactic acid) (PLA) is an important polymer that is based on renewable biomass resources. Because of environmental issues, more renewable sources for polymers synthesis have been sought for industrial purposes. In this sense, cheaper monomers should be used to facilitate better utilization of less valuable chemicals and therefore granting more sustainable processes. Some points are raised about the need to study the total degradability of any PLA, which may require specific composting conditions (e.g., temperature, type of microorganism, adequate humidity and aerobic environment). Polymerization processes to produce PLA are presented with an emphasis on D,L-lactic acid (or rac-lactide) as the reactant monomer. The syntheses involving homogeneous and heterogeneous catalytic processes to produce poly(D,L-Lactic acid) (PDLLA) are also addressed. Additionally, the production of blends, copolymers, and composites with PDLLA are also presented exemplifying different preparation methods. Some general applications of these materials mostly dedicated to the biomedical area over the last 10-15 years will be pointed out.

Microfluidic Production of Polymeric Core-Shell Microspheres for the Delayed Pulsatile Release of Bovine Serum Albumin as a Model Antigen.

For many vaccines, multiple injections are required to confer protective immunity against targeted pathogens. These injections often consist of a primer administration followed by a booster administration of the vaccine a few weeks or months later. A single-injection vaccine formulation that provides for both administrations could greatly improve the convenience and vaccinee's compliance. In this study, we developed parenterally injectable core-shell microspheres with a delayed pulsatile release profile that could serve as the booster in such a vaccine formulation. These microspheres contained bovine serum albumin (BSA) as the model antigen and poly(dl-lactide-co-glycolide) (PLGA) with various dl-lactide:glycolide monomer ratios as the shell material. Highly monodisperse particles with different particle characteristics were obtained using a microfluidic setup. All formulations exhibited a pulsatile in vitro release of BSA after an adjustable lag time. This lag time increased with the increasing lactide content of the polymer and ranged from 3 to 7 weeks. Shell thickness and bovine serum albumin loading had no effect on the release behavior, which could be ascribed to the degradation mechanism of the polymer, with bulk degradation being the main pathway. Co-injection of the core-shell microspheres together with a solution of the antigen that serves as the primer would allow for the desired biphasic release profile. Altogether, these findings show that injectable core-shell microspheres combined with a primer are a promising alternative for the current multiple-injection vaccines.

Recent developments in biomaterials for long-bone segmental defect reconstruction: A narrative overview.

Reconstruction of long-bone segmental defects (LBSDs) has been one of the biggest challenges in orthopaedics. Biomaterials for the reconstruction are required to be strong, osteoinductive, osteoconductive, and allowing for fast angiogenesis, without causing any immune rejection or disease transmission. There are four main types of biomaterials including autograft, allograft, artificial material, and tissue-engineered bone. Remarkable progress has been made in LBSD reconstruction biomaterials in the last ten years. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our aim is to summarize recent developments in the divided four biomaterials utilized in the LBSD reconstruction to provide the clinicians with new information and comprehension from the biomaterial point of view.

N-Hydroxysuccinimide Bifunctionalized Triblock Cross-Linker Having Hydrolysis Property for a Biodegradable and Injectable Hydrogel System.

The design of biocompatible, degradable, and injectable hydrogel has been attractive for achievement of safe and efficient tissue engineering. Herein, we designed a N-hydroxysuccinimide (NHS) ester-terminated ABA triblock copolymer composed of poly(ethylene glycol) (PEG) as hydrophilic A segments and poly(dl-lactide) (PLA) as B segment having hydrolysis property (NHS-PEG-b-PLA-b-PEG-NHS) to be a cross-linker of polymer segments having amine groups for facile construction of injectable and degradable hydrogel. The PLA domain, which is widely accepted hydrolyzable segments, is inherently hydrophobic and simple introduction of the NHS group on the ends of PLA would not have high reactivity in aqueous milieu to construct injectable hydrogel. Thus, in this design, hydrophilic PEG was introduced as A segments to increase the reactivity of NHS groups at the ends of linkers by increasing the mobility. To demonstrate the property as a cross-linker for constructing degradable and injectable hydrogel, carboxylmethyl chitosan (CH), which is a polymer segment having amine groups, and NHS-PEG-b-PLA-b-PEG-NHS solutions were mixed to form the hydrogel (CH/PEG-PLA-PEG) under physiological condition. The formation of CH/PEG-PLA-PEG hydrogel proceeded within minute-order period after mixing the solutions, suggesting NHS-PEG-b-PLA-b-PEG-NHS is applicable to the cross-linker for construction of injectable hydrogel system with time-dependent gelation property. Degradation of the obtained CH/PEG-PLA-PEG hydrogel was observed, whereas that of CH/PEG, which was prepared from NHS-PEG-NHS and CH, was not observed, appealing the degradation property of the CH/PEG-PLA-PEG hydrogel based on hydrolysis of the PLA domain. Furthermore, chondrocytes embedded in CH/PEG-PLA-PEG hydrogels promoted collagen synthesis compared to CH/PEG. These demonstrations indicate the designed NHS-PEG-b-PLA-b-PEG-NHS is a promising cross-linker to construct the injectable and degradable hydrogel and eventually promote hydrogel performance as a tissue regeneration scaffold.

Vertical ridge augmentation using a porous composite of uncalcined hydroxyapatite and poly-DL-lactide enriched with types 1 and 3 collagen.

BACKGROUND: Previous studies have shown that porous composite blocks containing uncalcined hydroxyapatite (u-HA; 70 wt%) with a scaffold of poly-DL-lactide (PDLLA, 30 wt%) are biodegradable, encourage appropriate bone formation, and are suitable for use as a bone substitute in vertical ridge augmentation. The present study aimed to accelerate osteogenesis in vertical ridge formation by adding types 1 and 3 collagen to the u-HA/PDLLA blocks and assessing the effect. MATERIAL AND METHODS: The bone substitute in the present study comprised porous composite blocks of u-HA (70 wt%) with a PDLLA (27-29 wt%) scaffold and enriched with types 1 and 3 collagen (1.7 ~ 3.4 wt%). The control blocks were composed of u-HA (70 wt%) and PDLLA (30 wt%). The materials were formed into 8-mm diameter, 2-mm high discs and implanted onto the cranial bones of six rabbits. The animals were sacrificed 4 weeks after implantation, and histological and histomorphometrical analyses were performed to quantitatively evaluate newly formed bone. RESULTS: New bone formation occurred with both block types, showing direct contact with the original bone. Mean ± standard deviation bone formation was significantly greater in the experimental blocks (25.6% ± 4.8%) than in the control blocks (17.0% ± 4.7%). CONCLUSIONS: Histological and histomorphometrical observations indicated that new bone was formed with both block types. The u-HA/PDLLA block with types 1 and 3 collagen is a more promising candidate for vertical ridge augmentation than the u-HA/PDLLA alone block.

Chitosan Coating Effect on Cellular Uptake of PLGA Nanoparticles for Boron Neutron Capture Therapy.

The usefulness of poly(lactide-co-glycolide) nanoparticles as a boron compound carrier for boron neutron capture therapy has been recently reported. In this study, chitosan-modified poly(DL-lactide-co-glycolide) (PLGA) nanoparticles were prepared to better facilitate the delivery of boron to the tumor. Chitosan hydroxypropyltrimonium chloride (CS), which can easily be modified for compatibility with PLGA nanoparticles, was used as chitosan. o-Carborane-loaded PLGA nanoparticles (bare nanoparticles) with a mean volume diameter of 111.4 ± 30.1 nm, and o-Carborane-loaded PLGA nanoparticles coated with CS (CS-coated nanoparticles) with a mean volume diameter of 113.6 ± 32.5 nm were prepared via an emulsion solvent evaporation method. Electrophoretic mobility was measured to calculate the particle surface charge number density of these particles; particle surface charge number densities of -1.91 mM and 20.8 mM were obtained for the bare and CS-coated nanoparticles, respectively. This result indicates that the particle surface was fully covered with CS. In vitro cellular uptake tests were carried out by using B16 melanoma cells. From the results of observation via confocal laser scanning microscopy, it was revealed that CS-coated nanoparticles existed around the cell nucleus, and were localized in the cytoplasm. Cellular uptakes of bare and CS-coated nanoparticles were quantitatively assessed by using fluorescence-activated cell sorting; the mean fluorescence intensity of CS-coated nanoparticles was three times higher than that of bare nanoparticles. The number of boron atoms in B16 melanoma cells was also investigated. Inductively coupled plasma atomic emission spectroscopy revealed that the number of boron atoms per cell of CS-coated nanoparticles was 1.8 times higher than that of bare nanoparticles. Based on these findings, we consider CS-coated nanoparticles to be suitable for boron neutron capture therapy.

Guided bone regeneration using a bone tissue engineering complex consisting of a poly-dl-lactide membrane and bone mesenchymal stem cells.

Developmental dysplasia of the hip (DDH) is one of the most common diseases encountered in pediatric orthopedic departments. Current treatment strategies seek to improve acetabular coverage, the principal defect of acetabular dysplasia, but are not very successful. We developed a guided bone regeneration (GBR) strategy to improve acetabular coverage via bone tissue engineering (BTE). Poly-dl-lactide (PDLLA) membranes were seeded with bone marrow mesenchymal stem cells (BMSCs) to form a BTE complex, which was then implanted into the superior margin of the acetabulum in a rabbit DDH model. Twelve weeks later, a small amount of high-density shadowing was evident on X-rays of the superior margin of the acetabulum, specimens of which exhibited new bone formation. Micro-computed tomography yielding three-dimensional images revealed that new bone had formed in the superior acetabulum, the basal part of which had fused with (and thus reconstructed) the autogenous bone, and new trabecular bone featuring transverse interlacing was evident in the interior of the hip. No clear evidence of bone formation was observed in rabbits that underwent sham operations or that were implanted with PDLLA only. Thus, it may be possible to improve acetabular coverage via BTE-based bone regeneration.

Therapeutic efficacy of rebamipide-loaded PLGA nanoparticles coated with chitosan in a mouse model for oral mucositis induced by cancer chemotherapy.

Oral mucositis is one of the most common side effects induced by cancer therapy, and the prevention or rapid treatment of the symptoms of oral mucositis can improve patients' quality of life and reduce the need for treatment interruption. In this study, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles coated with chitosan hydroxypropyltrimonium chloride was used as a carrier of rebamipide, and its usefulness was evaluated using a mouse model for oral mucositis. The surface properties and particle size of this nanoparticle were considered to be advantageous for the treatment of oral mucositis. Positively charged nanoparticles with an average particle diameter of 97.0 ±â€¯36.7 nm were prepared. From the results of the mucin adsorption study using a periodic acid/Schiff colorimetric method, it was confirmed that the mucin adsorptive capacity of chitosan-coated nanoparticles was 2.3 times higher than that of bare nanoparticles. This result was consistent with the results of the oral retention study of chitosan-coated nanoparticles using an in vivo optical imaging system. Therapeutic efficacy of the nanoparticles on oral mucositis was evaluated using a mouse model for oral mucositis induced by cancer chemotherapy. The chitosan-coated nanoparticles administration group significantly decreased the ulcer area at day 9, 11, and 13 compared with the non-treated control group. Moreover, this group significantly shortened the treatment period by 3.6 days compared to the bare nanoparticles administration group. Therefore, it was suggested that rebamipide-loaded PLGA nanoparticles coated with chitosan hydroxypropyltrimonium chloride were beneficial for the treatment of oral mucositis induced by cancer chemotherapy.

Preparation and Evaluation of Biodegradable Scleral Plug Containing Curcumin in Rabbit Eye.

BACKGROUND: To test whether biodegradable curcumin-loaded scleral plug is a promising choice for treating posterior ocular diseases, the study investigated the in vitro release profile of the scleral plug and its safety in vivo. METHODS: Scleral plugs containing 0.5 mg, 1.0 mg and 1.5 mg curcumin were synthesized by a compression-sintering method. These scleral plugs were placed in tubes containing balanced salt solution (BSS) buffer, which was replaced by fresh buffer daily. The curcumin concentration in the removed aliquot was tested daily for 14 days using high-performance liquid chromatography (HPLC). In the study, 44 rabbits were randomly divided into four groups: control, 0.5 mg, 1.0 mg and 1.5 mg curcumin groups. The scleral plug was trans-scleral fixed in the right eye of the rabbits in the three curcumin-treated groups. The control rabbits only received sclerotomy. The treated rabbit eyes were examined by a slit-lamp biomicroscope, an indirect ophthalmoscope and electroretinogram (ERG), and subjected to histological analysis. RESULTS: The concentration of the 1.5 mg curcumin-loaded scleral plug was higher than 15 µg/ml for consecutive 14 days in vitro. The in vivo experiments revealed intraocular pressure, a-wave and b-wave amplitudes of ERG, and conjunctival reaction degree were not significantly different between the four groups. Retinal structure was normal in the curcumin-treated groups. The sclerotomy wound healed after the plug was completely degraded. Anterior chamber reaction or complications were not observed. CONCLUSION: The study suggests that curcumin-loaded scleral plug could sustain high concentration of curcumin in vitro and is safe in vivo. It might be a promising alternative choice for the treatment of posterior ocular diseases.