Poly(lactic-co-glycolic) Acid Particles Research Articles

Sustained release system from PLGA particles co-encapsulated with inactivated influenza virus with natural killer T cell agonist α-galactosylceramide

Vaccines against influenza and many other infectious diseases require multiple boosters in addition to the primary dose to improve efficacy, but this approach is not ideal for compliance. The multiple doses could potentially be replaced by sustained or pulsatile release of antigens encapsulated in degradable microparticles (MPs). The efficacy of a vaccine is improved by adding an adjuvant, which can be co-delivered from the particles to enhance immunogenicity. Here, we developed degradable poly-lactic-co-glycolic acid (PLGA) (7–17 kDa) MPs capable of sustained release of ultraviolet killed influenza virus (A/PR/8/34) (kPR8) vaccine and the natural killer T (NKT) cell agonist alpha-galactosylceramide (α-GalCer) and tested their effectiveness at providing long-term protection against influenza virus infection in mice. Multiple formulations were developed for encapsulating the virus and adjuvant separately, and in combination. The MPs exhibited sustained release of both the virus and the adjuvant lasting more than a month. Co-encapsulation significantly increased the encapsulation efficiency (EE) of the vaccine but reduced the release duration. On the other hand, co-encapsulation led to a reduction in EE for the α-GalCer and a change in release profile to a higher initial burst followed by a linear release compared to a low initial burst and slower linear release. The α-GalCer also had considerably longer release duration compared to the vaccine. Mice injected with particle formulations co-encapsulating kPR8 and α-GalCer were protected from a lethal influenza virus infection 30 weeks after vaccination. This study demonstrates that PLGA MP based vaccines are promising for providing effective vaccination and possibly for replacing multiple doses with a single injection.

Microfluidic-Based Formulation of Essential Oils-Loaded Chitosan Coated PLGA Particles Enhances Their Bioavailability and Nematocidal Activity.

In this study, poly (lactic-co-glycolic) acid (PLGA) particles were synthesized and coated with chitosan. Three essential oil (EO) components (eugenol, linalool, and geraniol) were entrapped inside these PLGA particles by using the continuous flow-focusing microfluidic method and a partially water-miscible solvent mixture (dichloromethane: acetone mixture (1:10)). Encapsulation of EO components in PLGA particles was confirmed by Fourier transform infrared spectroscopy, thermogravimetric analysis, and X-ray diffraction, with encapsulation efficiencies 95.14%, 79.68%, and 71.34% and loading capacities 8.88%, 8.38%, and 5.65% in particles entrapped with eugenol, linalool, and geraniol, respectively. The EO components’ dissociation from the loaded particles exhibited an initial burst release in the first 8 h followed by a sustained release phase at significantly slower rates from the coated particles, extending beyond 5 days. The EO components encapsulated in chitosan coated particles up to 5 μg/mL were not cytotoxic to bovine gut cell line (FFKD-1-R) and had no adverse effect on cell growth and membrane integrity compared with free EO components or uncoated particles. Chitosan coated PLGA particles loaded with combined EO components (10 µg/mL) significantly inhibited the motility of the larval stage of Haemonchus contortus and Trichostrongylus axei by 76.9%, and completely inhibited the motility of adult worms (p < 0.05). This nematocidal effect was accompanied by considerable cuticular damage in the treated worms, reflecting a synergistic effect of the combined EO components and an additive effect of chitosan. These results show that encapsulation of EO components, with a potent anthelmintic activity, in chitosan coated PLGA particles improve the bioavailability and efficacy of EO components against ovine gastrointestinal nematodes.

The Evaluation of Bone Regeneration Following Socket Preservation with Concentrated Growth Factor (CGF) and Poly Lactic-Co-Glycolic Acid (PLGA) Scaffold in Rabbits

Various grafting materials are utilised to facilitate regeneration. There is currently a paradigm shift towards applying poly lactic-co-glycolic acid (PLGA), which is regarded as an excellent scaffold for tissue engineering. Concentrated growth factor (CGF) has also been reported to promote wound healing. Nevertheless, the role of PLGA microspheres as a substitute for bone graft material with CGF in bone regeneration remains unclear. This study was designed to evaluate the effect of CGF with PLGA on bone formation and the expression of alkaline phosphatase (ALP) following socket preservation. PLGA microspheres were prepared using double solvent evaporation method and observed under scanning electron microscopy (SEM). A 6 mL of rabbit’s blood was collected from the marginal ear vein and centrifuged to obtain CGF. Blood was also collected for ALP assessment from 24 New Zealand White (NZW) male rabbits subjected to the first upper left premolar extraction. Sockets were filled with CGF, PLGA, CGF+PLGA or left empty and observed with microscopic computed tomography (micro-CT) at four weeks and eight weeks. The SEM image revealed a spherical shape with interconnected pores on the surface of the PLGA particles. Repeated measures ANOVA were used to evaluate the effect of time and treatment (p &lt; 0.05) with significant differences in bone width, height, volume, volume fraction and expression of ALP was observed with CGF+PLGA. Both CGF and PLGA have the potential as the alternative grafting materials and this study could serve as an ideal benchmark for future investigations on the role of CGF+PLGA in bone regeneration enhancement.

Human fetal mesenchymal stem cells secretome promotes scarless diabetic wound healing through heat-shock protein family.

The high mortality rate of patients with diabetic foot ulcers is urging the appearance of an effective biomedical drug. Senescence is one of the major reasons of aging-induced decline in the diabetic wound. Our previous studies have demonstrated the anti-senescence effect of secretomes derived from human fetal mesenchymal stem cells (hfMSC). The present study tends to explore the potential role of hfMSC secretome (HFS) in wound healing through anti-aging. Meanwhile, we try to overcome several obstacles in the clinical application of stem cell secretome. A verticle bioreactor and microcarriers are employed to expand hfMSC and produce the HFS on a large scale. The HFS was then subjected to lyophilization (L-HFS). The PLGA (poly lactic-co-glycolic acid) particles were used to encapsulate and protect L-HFS from degradation in the streptozotocin (STZ)-induced diabetic rat model. Results showed that HFS-PLGA significantly enhanced wound healing by promoting vascularization and inhibiting inflammation in the skin wound bed. We further analyzed the contents of HFS. Isobaric tag for relative and absolute quantitation (ITRAQ) and label-free methods were used to identify peptides in the secretome. Bioinformatics analysis indicated that exosome production-related singling pathways and heat-shock protein family could be used as bio-functional markers and quality control for stem cell secretome production.

Size-dependent cellular uptake and sustained drug release of PLGA particles

Poly (lactic-co-glycolic) acid (PLGA) particles have become a commonly used drug delivery strategy in the pharmaceutical industry. In this work, we aim to investigate the size-dependent cellular internalization of PLGA particles and its effects on sustained drug release. We prepared three different-sized particles using PLGA (200, 500 and 2000 nm) ranging from submicrometer to micrometer. Dexamethasone (DEX) with excellent anti-inflammatory properties was used as a model drug to prepare DEX-loaded PLGA particles (DPs). We comprehensively investigated the encapsulation efficiency, cellular uptake and in vitro drug release profile. Pharmacodynamic assessment revealed that, in the lipopolysaccharide (LPS)-induced RAW 264.7 cells model, 500 nm DPs showed sustained anti-inflammatory efficacy. This work provides important information for designing PLGA-based drug delivery systems for biomedical applications.

The Acute Immune Responses of the Common Carp Cyprinus carpio to PLGA Microparticles-The Interactions of a Teleost Fish with a Foreign Material.

Poly lactic-co-glycolic acid (PLGA) particles safely and effectively deliver pharmaceutical ingredients, with many applications approved for clinical use in humans. In fishes, PLGA particles are being considered as carriers of therapeutic drugs and vaccine antigens. However, existing studies focus mainly on vaccine antigens, the endpoint immune responses to these (e.g., improved antibody titres), without deeper understanding of whether fishes react to the carrier. To test whether or not PLGA are recognized by or interact at all with the immune system of a teleost fish, we prepared, characterized and injected PLGA microparticles intraperitoneally into common carp. The influx, phenotype of inflammatory leukocytes, and their capacity to produce reactive oxygen species and phagocytose PLGA microparticles were tested by flow cytometry, qPCR, and microscopy. PLGA microparticles were indeed recognized. However, they induced only transient recruitment of inflammatory leukocytes that was resolved 4 days later whereas only the smallest µm-sized particles were phagocytosed. The overall response resembled that described in mammals against foreign materials. Given the similarities between our findings and those described in mammals, PLGA particles can be adapted to play a dual role as both antigen and drug carriers in fishes, depending on the administered dose and their design.

PLGA's Plight and the Role of Stealth Surface Modification Strategies in Its Use for Intravenous Particulate Drug Delivery.

Numerous human disorders can benefit from targeted, intravenous (IV) drug delivery. Polymeric nanoparticles have been designed to undergo systemic circulation and deliver their therapeutic cargo to target sites in a controlled manner. Poly(lactic-co-glycolic) acid (PLGA) is a particularly promising biomaterial for designing intravenous drug carriers due to its biocompatibility, biodegradability, and history of clinical success across other routes of administration. Despite these merits, PLGA remains markedly absent in clinically approvedIV drug delivery formulations. A prominent factor in PLGA particles' inability to succeed intravenously may lie in the hydrophobic character of the polyester, leading to the adsorption of serum proteins (i.e., opsonization) and a cascade of events that end in their premature clearance from the bloodstream. PEGylation, or surface-attached polyethylene glycol chains, is a common strategy for shielding particles from opsonization. Polyethylene glycol (PEG) continues to be regarded as the ultimate "stealth" solution despite the lack of clinical progress of PEGylated PLGA carriers. This review reflects on some of the reasons for the clinical failure of PLGA, particularly the drawbacks of PEGylation, and highlights alternative surface coatings on PLGA particles. Ultimately, a new approach will be needed to harness the potential of PLGA nanoparticles and allow their widespread clinical adoption.

The roadmap to micro: Generation of micron-sized polymeric particles using a commercial microfluidic system.

Microfluidic-assisted particle fabrication provides a route to circumvent the disadvantages associated with traditional methods of polymeric particle generation, such as low drug loading efficiency, challenges in controlling encapsulated drug release rates, batch-to-batch variability in particle physical properties and formulation instability. However, this approach primarily produces particles with nanometer size dimensions, which limits drug delivery modalities. Herein, we systematically studied parameters for the generation of micron-sized poly(lactic-co-glycolic) acid (PLGA) particles using a microfluidic system, the NanoAssemblr benchtop. Initially, we used two organic solvents that have been reported suitable for the fabrication of PLGA nanoparticles - acetone and acetonitrile. Subsequently, we methodically manipulated polymer concentration, organic: aqueous flow rate ratios, total flow rate, organic phase composition, and surfactant concentration to develop a route for the fabrication of micron-sized PLGA particles. Further, we incorporated hydroxychloroquine (HCQ), a clinically approved drug for malaria and lymphoma, and measured how its incorporation impacted particle physicochemical properties. Briefly, altering the organic phase composition by including ethyl acetate (less polar solvent), resulted in micron-scale particles, as well as increased polydispersity indexes (PDIs). Adjusting the surfactant concentration of poly vinyl alcohol (PVA) after the addition of these solvent mixtures rendered large particles with lower PDI variability. Moreover, encapsulation of HCQ influenced particle hydrodynamic diameter and PDI in a PVA concentration dependent manner. Finally, we demonstrated that unloaded and HCQ-loaded microparticles did not affect the viability of RAW 264.7 macrophages. This study provides an itinerary for fabricating biocompatible, drug-loaded, micron-sized polymeric particles, particularly when the drug of interest is not readily soluble in conventional organic solvents.

Screening of Surfactants for Improved Delivery of Antimicrobials and Poly-Lactic-co-Glycolic Acid Particles in Wound Tissue.

Topical wound management is often a challenge due to the poor penetration of antimicrobials in wound tissue and across the biofilm matrix where bacteria are embedded. Surfactants have been used for decades to improve the stability of formulations, increase drug solubility, and enhance penetration. In this study, we screened different detergents with respect to their cytotoxicity and their ability to improve the penetration of poly-lactic-co-glycolic acid (PLGA) particles in wound tissue. Among the tested surfactants, Kolliphor SLS and Tween 80 increased the penetration of PLGA particles and had a limited cytotoxicity. Then, these surfactants were used to formulate PLGA particles loaded with the poorly water-soluble antibiotic ciprofloxacin. The antimicrobial efficacy of the formulations was tested in a wound infection model based on human ex vivo skin. We found that even though PLGA particles had the same antimicrobial efficiency than the particle-free drug formulation, thanks to their solubilizing and anti-biofilm properties, the surfactants remarkably improved the antimicrobial activity of ciprofloxacin with respect to the drug formulation in water. We conclude that the use of Tween 80 in antimicrobial formulations might be a safe and efficient option to improve the topical antimicrobial management of chronic wound infections.

A Novel Method for Preparing Uniform-Sized PLGA Microspheres and the Application in Anti-tubercular Drug Delivery

The size was a key factor influencing the drug loading, release, and delivery efficacies of poly (lactic-co-glycolic) acid (PLGA) microspheres (MS). The purpose of the study was to explore a novel and simple method to prepare uniform-sized PLGA MS for drug delivery. Different from routine homogenizer, a vortex shaker was employed for emulsification during the preparation of PLGA MS. To enhance the homogeneity of resulted PLGA MS, a glass bead was used to facilitate the emulsification. The size of PLGA MS was controlled by adjusting the working frequency and time of vortex shaker. Then, selective centrifugation was used to further enrich PLGA MS of desired size. The resulted PLGA MS were systematically evaluated in anti-tubercular drug delivery. Compared with the routine stirring-based method, the novel method possessed a higher efficiency of emulsification and resulted in more homogenous MS under similar conditions. The produced PLGA particles were of a narrow size distribution, which could be 1 to 5 μm by adjusting the working frequency and time of vortex shaker. The narrow size distribution made it rather easy to enrich PLGA MS of specific size through selective centrifugation. Then, to evaluate the potential of the PLGA MS for drug delivery, 2–3-μm sized PLGA MS were selected to deliver anti-tubercular drug rifampicin (RFP). In vitro experiments demonstrated that the loaded RFP could be well-controlled release and delivered into macrophages. Anti-tubercular experiments showed that the uniform-sized MS as carriers of RFP significantly enhanced the therapeutic efficacy of the drug. Collectively, the study provided a novel and simple method for preparing uniform-sized PLGA MS, which may be of potentially wide applications.

Development and characterization of PLGA nanoparticles containing antibiotics

Several strategies for the delivery and release of drugs have been studied, among them the use of polymeric nanoparticles of PLGA (poly lactic-co-glycolic acid). These nanoparticles (NPs) have been shown to be promising for the controlled and effective release of drugs due to their biodegradability and biocompatibility. Regarding this, the aim of this study is to synthesize and characterize PLGA polymer nanoparticles associated with antimicrobials in order to reduce adverse reactions and to have a more effective local delivery. Empty PLGA nanoparticles and conjugated to vancomycin and meropenem antibiotics were synthesized by the double emulsification-solvent evaporation technique. Then, they were characterized by the analysis of the mean particle diameter, dynamic light scattering (DLS), Fourier transform infrared (FTIR) vibrational spectroscopy, contact angle measurement, and atomic force microscopy (AFM) and scanning electron microscopy (SEM). The DLS analysis of the NPs obtained showed approximate sizes of 263.5 nm (NPs-PLGA), 239.3 nm (NPs-VAN) and 284.2 nm (NPs-MER), and monodispersivity. FTIR results and contact angle measurements suggest encapsulation of antibiotics to NPs. The morphology evaluated through AFM and SEM indicates homogeneous, uniform, and spherical distribution of NPs and also apparently smooth. The antibacterial action of PLGA nanoparticles carried with antibiotics was effective when using concentrations of 5–2.5 mg/mL (PLGA-VAN) versus Staphylococcus aureus and 10–2.5 mg/mL (PLGA-MER) to Pseudomonas aeruginosa. The release kinetics of the antibiotics revealed a release profile of 43.9% at the end of 24 h and 96% at the end of 96 h for PLGA-VAN formulation and 8.25% and 16% at the end of 24 h and 96 h, for PLGA-MER, respectively. This study supports the potential application of PLGA particles containing antibiotics as facilitators of drug delivery and release effectively.

Repurposing rosiglitazone, a PPAR-γ agonist and oral antidiabetic, as an inhaled formulation, for the treatment of PAH

Peroxisome-proliferator-activated-receptor-gamma (PPAR-γ) is implicated, in some capacity, in the pathogenesis of pulmonary arterial hypertension (PAH). Rosiglitazone, an oral antidiabetic and PPAR-γ agonist, has the potential to dilate pulmonary arteries and to attenuate arterial remodeling in PAH. Here, we sought to test the hypothesis that rosiglitazone can be repurposed as inhaled formulation for the treatment of PAH. We have tested this conjecture by preparing and optimizing poly(lactic-co-glycolic) acid (PLGA) based particles of rosiglitazone, assessing the drug particles for pulmonary absorption, investigating the efficacy of the plain versus particulate drug formulation in improving the respiratory hemodynamics in PAH animals, and finally studying the effect of the drug in regulating the molecular markers associated with PAH pathogenesis. The optimized particles were slightly porous and spherical, and released 87.9% ± 6.7% of the drug in 24 h. The elimination half-life of the drug formulated in PLGA particles was 2.5-fold greater than that of the plain drug administered via the same route at the same dose. The optimized formulation, given via the pulmonary route, produced pulmonary selective vasodilation in PAH animals, but oral rosiglitazone had no effect in pulmonary hemodynamics. Rosiglitazone ameliorates the pathogenesis of PAH by balancing the molecular regulators involved in the vasoconstriction and vasodilation of human pulmonary arterial smooth muscle cells. All in all, data generated using intact animal and cellular models point to the conclusion that PLGA particles of an antidiabetic drug can be used for the treatment of a different disease, PAH.

Ramizol® encapsulation into extended release PLGA micro- and nanoparticle systems for subcutaneous and intramuscular administration: in vitro and in vivo evaluation

Objective: Novel antibiotic Ramizol® is advancing to clinical trials for the treatment of gastrointestinal Clostridium difficile associated disease. Despite this, previous studies have shown a rapid plasma clearance upon intravenous administration and low oral bioavailability indicating pure drug is unsuitable for systemic infection treatment following oral dosing. The current study aims to investigate the development of poly-lactic-(co-glycolic) acid (PLGA) particles to overcome this limitation and increase the systemic half-life following subcutaneous and intramuscular dosing.Significance: The development of new antibiotic treatments will help in combatting the rising incidence of antimicrobial resistance.Methods: Ramizol® was encapsulated into PLGA nano and microparticles using nanoprecipitation and emulsification solvent evaporation techniques. Formulations were analyzed for particle size, loading level and encapsulation efficiency as well as in vitro drug release profiles. Final formulation was advanced to in vivo pharmacokinetic studies in Sprague–Dawley rats.Results: Formulation technique showed major influence on particle size and loading levels with optimal loading of 9.4% and encapsulation efficiency of 92.06%, observed using emulsification solvent evaporation. Differences in formulation technique were also linked with subsequent differences in release profiles. Pharmacokinetic studies in Sprague–Dawley rats confirmed extended absorption and enhanced bioavailability following subcutaneous and intramuscular dosing with up to an 8-fold increase in Tmax and T1/2 when compared to the oral and IV routes.Conclusions: Subcutaneous and intramuscular dosing of PLGA particles successfully increased systemic half-life and bioavailability of Ramizol®. This formulation will allow further development of Ramizol® for systemic infection eradication.

Ketamine nano-delivery based on poly-lactic-co-glycolic acid (PLGA) nanoparticles

This work describes a novel method for the generation of a ketamine nano-delivery, to improve brain blood barrier permeability and increase drug therapeutic window as anaesthetic, analgesic and potential antidepressant. The approach herein described is based on ketamine-loaded poly-lactic-co-glycolic acid (PLGA) nanoparticles coupled to an apolipoprotein E (ApoE) peptide for delivery to the central nervous system. PLGA particles were synthesized with amount of drug, coupled with the ApoE peptide on the surface, and validated by physical characterization. The produced nanodevice showed a good colloidal stability in water, confirmed by zeta potential measurements, with a diameter in the range of 185–205 nm. The ketamine encapsulation was verified by liquid chromatography–mass spectrometry analyses obtaining an encapsulation efficiency up to 21.2 ± 3.54%. Once the occurrence of ApoE peptide functionalization was confirmed with fluorescence spectroscopy, the thermal stability and morphological information were obtained by differential scanning calorimetry and further dynamic light scattering measurements. The spherical shape and a rough nanoparticles surface were observed by atomic force microscopy. The reliability of this approach may be further developed as a protocol to be used to generate PLGA nanoparticles greater than 100 nm able to better penetrate blood brain barrier and release a neuroactive molecule at lower doses.

Modeling of the burst release from PLGA micro- and nanoparticles as function of physicochemical parameters and formulation characteristics

A substantial drug release from poly(lactic-co-glycolic) acid (PLGA) micro- and nanoparticles can occur in the first hours of immersion, which is referred to as burst release. A strong burst release (when not intentional) is to be avoided as it decreases the efficacy of the treatment and could be dangerous to the host. In this work we analyze the total amount of drug released during burst and respective kinetics in relation to formulations characteristics, experimental conditions and drug molecular properties in 154 drug release experiments with 41 different drugs by partial least squares (PLS) and decision tree regression. The model created enables to quantify to which degree the physicochemical parameters control the burst release from PLGA particles. Our analysis shows that the amount of drug released during burst is mostly influenced by the formulation characteristics and the synthesis parameters, whereas the drug release kinetics is also influenced by the molecular properties of the drug. The variables that significantly influence the amount and kinetics of the burst release are discussed in detail and compared with findings from other researchers. The final regression models are shown to predict the release profile of a new drug, opening the possibility to be applied to systematically manipulate the burst release by means of designing an optimized drug delivery system.

Porous Nanohydroxyapatite/Collagen Scaffolds Loading Insulin PLGA Particles for Restoration of Critical Size Bone Defect.

Insulin is considered to be a classical central regulator of energy homeostasis. Recently, the effect of insulin on bone has gained a lot of attention, but little attention has been paid to the application in bone tissue engineering. In this study, porous nanohydroxyapatite/collagen (nHAC) scaffolds incorporating poly lactic-co-glycolic acid (PLGA) particles were successfully developed as an insulin delivery platform for bone regeneration. Bioactive insulin was successfully released from the PLGA particles within the scaffold, and the size of the particles as well as the release kinetics of the insulin could be efficiently controlled through Shirasu porous glass premix membrane emulsification technology. It was indicated that the nHAC/PLGA composite scaffolds possessed favorable mechanical and structural properties for cell adhesion and proliferation, as well as the differentiation into osteoblasts. It was also demonstrated that the nHAC/PLGA scaffolds implanted into a rabbit critical-size mandible defect possessed tissue compatibility and higher bone restoration capacity compared with the defects that were filled with or without nHAC scaffolds. Furthermore, the in vivo results showed that the nHAC/PLGA scaffolds which incorporated insulin-loaded microspheres with a size of 1.61 μm significantly accelerated bone healing compared with two other composite scaffolds. Our study indicated that the local insulin released at the optimal time could substantially and reproducibly improve bone repair.

Efficacy of Poly-Lactic-Co-Glycolic Acid Micro- and Nanoparticles of Ciprofloxacin Against Bacterial Biofilms

Bacterial biofilms are associated with a number of recurring infectious diseases and are a major cause for antibiotic resistance. Despite the broad use of polymeric microparticles and nanoparticles in biomedical research, it is not clear which particle size is more effective against biofilms. The purpose of this study was to evaluate the efficacy of sustained release poly-lactic-co-glycolic acid (PLGA) micro- and nanoparticles containing ciprofloxacin against biofilms of Staphylococcus aureus and Pseudomonas aeruginosa. The PLGA particles were prepared by the double emulsion solvent evaporation method. The resulting microparticles (12 μm) and nanoparticles (300 nm) contained drug loads of 7.3% and 4.5% (wt/wt) ciprofloxacin, respectively. Drug release was complete within 1 week following comparable release profiles for both particle sizes. Micro- and nanoparticles demonstrated a similar in vitro antibiofilm performance against mature P aeruginosa and S aureus with marked differences between the 2 strains. The sustained release of ciprofloxacin from micro- and nanoparticles over 6 days was equally effective as the continuous treatment with ciprofloxacin solution over the same period resulting in the eradication of culturable S aureus suggesting that reformulation of ciprofloxacin as sustained release PLGA micro- and nanoparticles might be valuable formulation approaches for the treatment of biofilms.

Direct and controllable preparation of uniform PLGA particles with various shapes and surface morphologies

Abstract Biodegradable polymeric particles have been widely used in the biomedical fields such as drug carriers, tissue engineering, and medical imaging. It has been recognized that the physical properties of particles, such as size and shape, have a profound influence on their functions. However, it is not easy to prepare non-spherical particles by the conventional emulsion-based method because the minimization of interfacial energy leads to the spontaneous formation of spherical emulsions and it is difficult to control the uniformity and size. In order to solve this problem, we developed a direct method to fabricate non-spherical polylactic-co-glycolic acid (PLGA) particles with uniform size. This method employed a common agent, phosphate buffer saline (PBS), as the deformation initiator and combined the premix membrane emulsification technique with the solvent evaporation method to prepare uniform non-spherical particles of various shapes with aspect ratios from 2 to 40 and various sizes ranging from 800 nm to 60 μm (long axis). We found that the external driving force of stirring and the interfacial tension of the droplet dictated by the constitution of PBS and polyvinyl alcohol (PVA) have synergistic effects on the deformation. Through confocal laser microscopy (CLSM), the deforming process was observed visually in the solvent and gel state during the solidification. Moreover, octreotide acetate as a model peptide was successfully encapsulated into the non-spherical particles. The results indicated that the deformation process did not influence the encapsulation efficiency and bioactivity of the peptide, proving the feasibility of using non-spherical particles as potential drug delivery systems.

Effects of BDNF-loaded poly (lactide-co-glycolide) nanoparticle on hBMEC cell viability and its effectiveness in penetrating the BBB model

Event Abstract Back to Event Effects of BDNF-loaded poly (lactide-co-glycolide) nanoparticle on hBMEC cell viability and its effectiveness in penetrating the BBB model Siti N. Kamarudin1*, Gabriele R A Froemming2, Minaketan Tripathy3, Igor Iezhitsa4, Renad N Alyautdin5 and Nafeeza Mohd Ismail1 1 University Teknologi Mara (UiTM), Pharmacology/ Faculty of Medicine, Malaysia 2 University Teknologi Mara (UiTM), IPPerForM / Faculty of Medicine, Malaysia 3 University Teknologi Mara (UiTM), Fundamental of Pharmaceutics / Faculty of Pharmacy, Malaysia 4 University Teknologi Mara (UiTM), Centre for Neuroscience Research, Faculty of Medicine, Malaysia 5 Ministry of Health Russian Federation , Scientific Centre for Expertise of Medical Application Products, Russia Poly lactic-co-glycolic acid (PLGA) based nanoparticles are considered to be a promising drug carrier due to their extensive bioavailability, better encapsulation, controlled release properties and low cytotoxicity. Brain Derived Neurotrophic Factor (BDNF) is beneficial to brain tissue especially after ischemic injury promoting the survival of mature neuron cells. The objectives of this research were: 1) to prepare BDNF-loaded PLGA NPs coated with Apolipoprotein E (ApoE) to enhance BBB crossing via LDL-receptor mediated endocytosis; 2) to evaluate in vitro intracellular uptake and possible cytotoxicity of NPs using hBMEC cell line. Cell viability was determined using MTS-assay and cellular uptake of the NPs by the hBMEC cells was investigated using coumarin 6 as a fluorescent probe. For cells toxicity experiments, 5×104 cells per well were cultured in 96-well plates. After 4 hrs incubation with PLGA particles, 20 µl CellTiter 96s Aqueous One Solution was added directly to the cells and the formation of formazan was measured. Percentage of viability has been calculated relative to untreated control. For penetration study, 1×105 cells per well were cultured in 2 well chamber slides. After 4 hrs incubation, the nuclei were stained with DAPI; the cells were fixed and then imaged by CLSM to visualize the internalization of NPs. Totally 50 cells were analyzed using Leica Qwin software. The fluorescence intensity of the coumarin was measured according to its wavelength. Cell viability increased by 10.4% and 10.1% compared to control after exposure of hBMEC to PLGA-BDNF and PLGA-BDNF-ApoE respectively (p<0.001). Cellular uptake of PLGA-BDNF-ApoE was found to be significantly higher than PLGA-BDNF. In conclusion, PLGA-BDNF nanoparticles does not cause toxicity to hBMEC and was able to penetrate the cells. The penetration was enhanced by addition of ApoE on the surface of PLGA nanoparticles. Acknowledgements We would like to acknowledge the financial support from grant 600-RMI/ERGS 5/3 (36/2013) by MOE, Malaysia. Keywords: Blood-Brain Barrier, Vitamin E, Toxicity, in vitro, nanoparticle Conference: 14th Meeting of the Asian-Pacific Society for Neurochemistry, Kuala Lumpur, Malaysia, 27 Aug - 30 Aug, 2016. Presentation Type: Poster Presentation Session Topic: 14th Meeting of the Asian-Pacific Society for Neurochemistry Citation: Kamarudin SN, Froemming G, Tripathy M, Iezhitsa I, Alyautdin R and Mohd Ismail N (2016). Effects of BDNF-loaded poly (lactide-co-glycolide) nanoparticle on hBMEC cell viability and its effectiveness in penetrating the BBB model. Conference Abstract: 14th Meeting of the Asian-Pacific Society for Neurochemistry. doi: 10.3389/conf.fncel.2016.36.00153 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 04 Aug 2016; Published Online: 11 Aug 2016. * Correspondence: Dr. Siti N Kamarudin, University Teknologi Mara (UiTM), Pharmacology/ Faculty of Medicine, Sg Buloh, Selangor, Malaysia, syafika84@yahoo.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Siti N Kamarudin Gabriele R A Froemming Minaketan Tripathy Igor Iezhitsa Renad N Alyautdin Nafeeza Mohd Ismail Google Siti N Kamarudin Gabriele R A Froemming Minaketan Tripathy Igor Iezhitsa Renad N Alyautdin Nafeeza Mohd Ismail Google Scholar Siti N Kamarudin Gabriele R A Froemming Minaketan Tripathy Igor Iezhitsa Renad N Alyautdin Nafeeza Mohd Ismail PubMed Siti N Kamarudin Gabriele R A Froemming Minaketan Tripathy Igor Iezhitsa Renad N Alyautdin Nafeeza Mohd Ismail Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Conducting polymer microspherical cups for organic bioelectronics

Event Abstract Back to Event Conducting polymer microspherical cups for organic bioelectronics Milad Khorrami1, Martin Antensteiner1 and Mohammad Reza Abidian1 1 University of Houston, Biomedical Engineering, United States Current metallic-based implantable microscale bioelectronics have high impedance and low charge storage capacity, which result in both low signal-to-noise ratio and low charge injection electrode-tissue interfaces. Moreover, these electrodes without anti-inflammatory compounds are less likely to maintain their functionality due to unfavorable reactive tissue responses. Therefore, there is need to produce devices capable of delivering therapeutic compounds while maintaining their electrical performance. Poly(pyrrole) (PPy) has gained significant interest for biomedical applications owing to its excellent biocompatibility, electrical properties, and mechanical actuation. Poly(lactic-co-glycolic) acid (PLGA) is biodegradable and highly biocompatible, making it an ideal matrix for drug encapsulation. In this study, we have produced PPy microspherical cups from template PLGA microspheres. These conductive microstructures have large surface areas, granting low impedance values and high charge storage capacities for bioelectronics applications. PPy, poly(styrenesulfonate), benzyltriethylammonium chloride, PLGA, silicon wafer (Si) substrates and chloroform were used as purchased. Gold (Au) electrodes were fabricated on Si wafers (two circles with diameters 1.5mm and 5.0mm connected with a rectangle 1mm X 10mm). A thin layer of titanium (10nm) was deposited to support Au layer (100nm). Briefly, 4/2wt% PLGA/BTEAC was dissolved in chloroform and sprayed onto the Si using an applied electrical field of 100kVm-1 and 500μl/hr flow rate. PLGA particles were then coated with PPy/PSS using electrochemical deposition with current density 0.5mA/cm2 for 5 different time durations. The PLGA cores were then dissolved in chloroform to create PPy microspherical cups. Impedance spectroscopy (IS) and cyclic voltammetry (CV) were performed on all samples and a gold reference to investigate the impedance and charge storage capacity. The size and shape of PPy microstructures were characterized using Scanning Electron Microscopy. Fig. 1 shows the electropolymerized PPy on the surface of Au electrodes and around PLGA microspheres after 1, 2, 4, and 6 min. Fig. 2 demonstrates PPy cups after removal of PLGA cores. Fig. 3A shows the IS data for bare Au, PPy cups, and fully PPy-coated PLGA cores (8 min of deposition) from 1 to 10kHz. Electrodeposition of PPy on PLGA cores followed by removal of the PLGA significantly decreased the bare Au impedance (e.g. from 445 ± 63 Ω to 354 ± 39 Ω for 8 min coating at 1kHz, a difference of 20%). The additional surface area obtained by removal of the PLGA cores significantly increased the effective surface area of electrode, thus lowering the impedance. Fig. 3B shows the CV for bare gold, PPy cups, and fully PPy-coated PLGA microspheres. The PPy coating significantly increased the charge storage capacity from 2.5mC/cm2 (bare gold) to 47.5mC/cm2 (8 min), an increase of nearly 95%. We successfully demonstrated: (1) electrochemical deposition of PPy around the electrosprayed PLGA microspheres, (2) degradation of PLGA microspheres to fabricate PPy microspherical cups, and (3) improvement of electrical properties of Au electrodes by decreasing impedance and increasing charge storage capacity. This study demonstrates the potential of our conductive microstructures for neural interfacing and neural regeneration while retaining functionality for drug delivery. The authors would like to thank Fatemeh Fallahianbijan and support from National Institute of Health R01 NS087224. Keywords: electric, microstructure, polymer, biomedical application Conference: 10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016. Presentation Type: Poster Topic: Regenerative medicine: biomaterials for control of tissue induction Citation: Khorrami M, Antensteiner M and Abidian M (2016). Conducting polymer microspherical cups for organic bioelectronics. Front. Bioeng. Biotechnol. Conference Abstract: 10th World Biomaterials Congress. doi: 10.3389/conf.FBIOE.2016.01.02641 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Mar 2016; Published Online: 30 Mar 2016. Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Milad Khorrami Martin Antensteiner Mohammad Reza Abidian Google Milad Khorrami Martin Antensteiner Mohammad Reza Abidian Google Scholar Milad Khorrami Martin Antensteiner Mohammad Reza Abidian PubMed Milad Khorrami Martin Antensteiner Mohammad Reza Abidian Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. 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