Poly Lactic Acid Microparticles Research Articles

Polylactic acid microparticles in the range of μg/L reduce reproductive capacity by affecting the gonad development and the germline apoptosis in Caenorhabditis elegans

Polylactic acid (PLA) accounts for approximately 45% of the global market of biodegradable plastics. Using Caenorhabditis elegans as an animal model, we examined the effect of long-term exposure to PLA microplastic (MP) on reproductive capacity and the underlying mechanism. Brood size, number of fertilized eggs in uterus, and number of hatched eggs were significantly reduced by exposure to 10 and 100 μg/L PLA MP. Number of mitotic cells per gonad, area of gonad arm, and length of gonad arm were further significantly decreased by exposure to 10 and 100 μg/L PLA MP. In addition, exposure to 10 and 100 μg/L PLA MP enhanced germline apoptosis in the gonad. Accompanied with the enhancement in germline apoptosis, exposure to 10 and 100 μg/L PLA MP decreased expression of ced-9 and increased expressions of ced-3, ced-4, and egl-1. Moreover, the induction of germline apoptosis in PLA MP exposed nematodes was suppressed by RNAi of ced-3, ced-4, and egl-1, and strengthened by RNAi of ced-9. Meanwhile, we did not detect the obvious effect of leachate of 10 and 100 μg/L PLA MPs on reproductive capacity, gonad development, germline apoptosis, and expression of apoptosis related genes. Therefore, exposure to 10 and 100 μg/L PLA MPs potentially reduces the reproductive capacity by influencing the gonad development and enhancing the germline apoptosis in nematodes.

Study on Adsorption of Essential Oils on Polylactic Acid Microparticles

Polylactic acid (PLA) is a biodegradable polymer that is widely used in medical devices, drug delivery systems, fibers for packaging containers and textiles. However, given that interactions between the polymer and the materials in contact with it affect its applications, it is important to study its adsorption and diffusion properties. The adsorption capacity of different polylactic acid particles regarding different additives, e.g. essential oils (Thymus vulgaris, Melissa officinalis and Foeniculum vulgare), was investigated. PLA microparticles of various sizes were prepared by a solvent emulsification evaporation method. In this study, the specific adsorption of essential oils on PLA microparticles was also investigated, which is related to the solubility parameters of essential oils. The experiments were performed using three different solutions of essential oils and ethanol as a solvent. Two sets of PLA microparticles were prepared with different solvents using three different particle sizes. PLA microparticles exhibited different adsorption properties depending on the solvent that was used for their production. Samples of particles prepared using the solvent dichloromethane had a higher essential oil uptake than those prepared with chloroform. The uptake of essential oil solution did not change significantly (∼60%) by varying either the type of solvent used for PLA preparation or PLA particle size. The solubility of the essential oils affects the specific adsorption of essential oils on the microparticles. Among the components of the Hansen solubility parameters (HSPs), the polarity of essential oils is strongly related to adsorption.

Adsorption Properties of Essential Oils on Polylactic Acid Microparticles of Different Sizes.

The interaction between the polymer and the materials in contact with it affects its applicability. This can be particularly important in applications such as packaging or controlled drug delivery systems. Because of these interactions, the adsorption and diffusion properties of polylactic acid (PLA) are important. The absorption capacity of different polylactic acid particles for different additives like essential oils (Thymus vulgaris, Melissa officinalis, and Foeniculum vulgare essential oils) was investigated depending on the concentration of the essential oil. The PLA microparticles were prepared by the solvent evaporation emulsification method. The prepared particles had a degree of crystallinity of 0.1% and 16.1%, respectively, according to the granules used. This affects the particles’ adsorption properties. The specific essential oil uptake of the more crystalline microparticles was on average 15% higher than that of the amorphous particles. The specific amount of essential oil adsorbed decreases with the decreasing concentration of essential oil in the solutions. We also investigated whether the amount of essential oil taken up was correlated with the solubility parameter of the essential oils. We concluded that the difference between the adsorption of the essential oils on the polymer was related to the essential oils’ Hansen solubility parameter.

Production, Optimization and Characterization of Polylactic Acid Microparticles Using Electrospray with Porous Structure

Polymeric microparticles with controlled morphologies and sizes are being studied by researchers in many applications, such as for drug release, healthcare and cosmetics. Herein, spherical and porous polymeric microparticles of different sizes and morphologies by electrospray technique have been developed as a viable alternative. In this work, polylactic acid (PLA) microparticles with a spherical shape and porous morphology were successfully produced via an electrospray technique in a single step. Molecular interactions between the components and the effect of parameters, such as varying solvent compositions, flow rates and voltage on microparticle morphology, were investigated over the particle formation. It was observed that the type of solvents used is the most effective parameter in terms of particle morphology, size and distribution. When the optical microscopy and SEM images of the microparticles were examined, 3 wt.% PLA in dichloromethane (DCM) solution concentration with an applied voltage of 18 kV and a flow rate of 20 µL/min was found to be the optimum parameter combination to achieve the desired spherical and porous micron-size particles. The average diameter of the particles achieved was 3.01 ± 0.58 µm. DCM was found to be a more suitable solvent for obtaining microparticles compared to the other solvents used. Finally, particles that are obtained by electrospraying of PLA–DCM solution are porous and monodisperse. They might have excellent potential as a carrier of drugs to the targeted sides and can be used in different biomedical applications.

Are bio-based and biodegradable microplastics impacting for blue mussel (Mytilus edulis)?

The substitution of petrochemical plastics by bio-based and biodegradable plastics are in need of an evaluation for the potential toxic impacts that they can have on marine wildlife. This study aims to assess the toxicological effects of polylactic acid microparticles at two concentrations, 10 and 100 μg/L, during 8 days on the blue mussel, Mytilus edulis. No significant oxidative stress (catalase, glutathione-S-transferase and superoxide dismutase activities), neurotoxicity (acetylcholinesterase), or immunotoxicity (lysosomal membrane stability and acid phosphatase activity) were detectable. The multivariate analysis of metabolomic data allowed us to differentiate the individuals according to the exposure. From the loading plot of OPLS-DA, 48 ions down-regulated in the individuals exposed to microplastics. They were identified based on HRMS data as glycerophospholipids.

Engineered microtissues for the bystander therapy against cancer

Thymidine kinase expressing human adipose mesenchymal stem cells (TK-hAMSCs) in combination with ganciclovir (GCV) are an effective platform for antitumor bystander therapy in mice models. However, this strategy requires multiple TK-hAMSCs administrations and a substantial number of cells. Therefore, for clinical translation, it is necessary to find a biocompatible scaffold providing TK-hAMSCs retention in the implantation site against their rapid wash-out. We have developed a microtissue (MT) composed by TKhAMSCs and a scaffold made of polylactic acid microparticles and cell-derived extracellular matrix deposited by hAMSCs. The efficacy of these MTs as vehicles for TK-hAMSCs/GCV bystander therapy was evaluated in a rodent model of human prostate cancer. Subcutaneously implanted MTs were integrated in the surrounding tissue, allowing neovascularization and maintenance of TK-hAMSCs viability. Furthermore, MTs implanted beside tumors allowed TK-hAMSCs migration towards tumor cells and, after GCV administration, inhibited tumor growth. These results indicate that TK-hAMSCs-MTs are promising cell reservoirs for clinical use of therapeutic MSCs in bystander therapies.

Photocatalytic Nanocomposite Microsponges of Polylactide–Titania for Chemical Remediation in Water

We developed a simple and environmentally friendly approach for synthesis of photocatalytic nanocomposites composed of porous polylactic acid microparticles (PLA) with incorporated anatase titania ...

Development of an oxygen-releasing electroconductive in-situ crosslinkable hydrogel based on oxidized pectin and grafted gelatin for tissue engineering applications

Injectable hydrogels with conductivity are highly desirable as scaffolds for the engineering of various electrical stimuli-responsive tissues, including nerve, muscle, retina, and bone. However, oxygen deprivation within scaffolds can lead to failure by causing cell necrosis. Therefore, an oxygen release conductive injectable hydrogel can serve as a promising support for the regeneration of such tissues. In the present study, H2O2-loaded polylactic acid microparticles were fabricated. Then, gelatin-graft-polypyrrole with various pyrrole contents and periodate-oxidized pectin were synthesized, and consequently, injectable conductive hydrogel/microparticle scaffolds, inside which catalase was grafted and trapped, were obtained. The results revealed that spherical particles with a mean diameter of 60.39 μm and encapsulation efficiency of 49.64 %, which persistently provided oxygen up to 14 days, were achieved. Investigations on hydrogels revealed that with the increase of pyrrole content of gelatin-graft-polypyrrole from 0 to 15 %, the swelling ratio, pore size, porosity, and conductivity were increased from 6.5 to 11.8, 173.13 μm–295.96 μm, 79.7%–93.8%, and from 0.06 mS/m to 2.14 mS/m, respectively. On the other hand, the crosslinking degree and compressive modulus of hydrogels were shown to decrease from 67.24%–27.35%, and from 214.1 kPa to 64.4 kPa, respectively. Moreover, all formulations supported cell viability and attachment. Overall, the hydrogel/particle scaffold with the merits of electrical conductivity, injectability, compatibility, and sustained oxygen release can be used as a tissue engineering scaffold, promoting the regeneration of electricity responsive tissues. Considering all the aforementioned characteristics and behavior of the fabricated scaffolds, they may be promising candidates for bone tissue engineering applications.

Potential effects of biodegradable single-use items in the sea: Polylactic acid (PLA) and solitary ascidians

With conventional plastics posing a great threat to marine organisms, and potentially also to humans, bio-based, biodegradable plastics are being offered as an ecological solution by which to reduce the environmental impact. Inside compost facilities, bioplastics that comply with the EN 13432:2000 international standard biodegrade almost completely within 180 days. However, outside compost facilities, and specifically in marine environments, these bioplastics may have a similar effect to that of fossil-fuel based plastics. Here we investigated the effects of polyethylene terephthalate (PET) and polylactic acid (PLA) single-use cups and plates on a solitary ascidian’s biological and ecological features. Both PET and PLA microparticles reduced the fertilization rate of Microcosmus exasperatus, with no significant difference between materials. Accumulation rates in adult M. exasperatus exposed to micronized PET and PLA particles at two concentrations were similar for both the bioplastic material and the conventional plastic particles, with no significant difference between the two materials. A microbial-based digestive protocol was developed in order to recover the bioplastic material from ascidian tissue and reduce any material-loss caused by the known digestion protocols. Finally, PET plates submerged for three months in the Red Sea exhibited a significantly higher community richness and cover area in comparison to PLA plates, which did not provide a firm substrate for settlers. Indeed, coverage by the solitary ascidian Herdmania momus was significantly higher on PET plates. The current study demonstrates that discarded bioplastic products may have similar effects to those of conventional plastics on marine organism fertilization and biological accumulation, emphasizing the need to revise both the production and marketing of “biodegradable” and “compostable” plastics in order to prevent a further negative impact on ecosystems due to the mismanagement of bioplastic products.

Polylactic acid microparticles embedded porous gelatin scaffolds with multifunctional properties for soft tissue engineering

Suitable three-dimensional scaffolds showing controllable drug delivery properties, known as multifunctional scaffolds, have gained increasing interest for soft tissue engineering. Here, tetracycline hydrochloride-encapsulated polylactic acid (TCH-PLA) microparticles prepared by using the double emulsion/solvent evaporation method were incorporated into a gelatin matrix. Highly interconnected porous TCH-PLA-in-Gel scaffolds were formed by using lyophilization. In vitro release studies showed that the scaffolds exhibit a controlled release behavior and release low amounts of the drug. TCH-PLA particles additionally reinforced porous gelatin scaffolds and enhanced thermal stability. Antibacterial activity of the scaffolds against Staphylococcus aureus and Escherichia coli was confirmed by using the disk diffusion method. The scaffolds exhibited biocompatibility with adult human dermal fibroblasts, without cytotoxicity. Results indicated that TCH-PLA-in-Gel scaffolds showing multifunctional properties are good candidates for the applications of soft tissue engineering.

Triamcinolone acetonide-loaded PLA/PEG-PDL microparticles for effective intra-articular delivery: synthesis, optimization, in vitro and in vivo evaluation

Nowadays the use of sustainable polymers as poly-lactic acid (PLA) and poly-δ-decalactone (PDL) in drug delivery is advantageous compared to polymers derived from fossil fuels. The present work aimed to produce microparticles (MPs) derived from novel sustainable polymers, loaded with triamcinolone acetonide (TA) for treatment of rheumatoid arthritis via intra-articular (IA) delivery. PDL was synthesized from green δ-decalactone monomers and co-polymerized with methoxy-polyethylene glycol (mPEG) forming PEG-PDL with different molecular weights. The Hansen's solubility parameters were applied to select the most compatible polymer with the drug. An o/w emulsion/solvent evaporation technique was used for MPs fabrication, using 3 [3] full factorial design. Selection of the optimized MPs was performed using Expert Design® software's desirability function. The optimized formulations were characterized using scanning electron microscope, powder X-ray diffraction, differential scanning calorimetry, infrared spectroscopy and in vitro release studies. The inhibition percents of inflammation and histopathological studies were assessed in complete Freund's adjuvant-induced rats' knee joints evaluating the effect of IA injections of selected MPs compared to the free drug suspension. Solubility studies revealed high compatibility and miscibility between TA and PEG-PDL1700, which was blended with PLA for convenient MPs formation. The in vitro characterization studies confirmed the formation of drug-copolymer co-crystals. The in vivo studies ensured the superiority of the newly designed composite MPs in inflammation suppression, compared to the free drug suspension and PLA MPs as well. The present study proved the advantage of using sustainable polymers in a novel combination for effective drug delivery and suggesting its usefulness in designing versatile platforms for therapeutic applications.

Synthesis, characterization and antibacterial activity of thymol-loaded polylactic acid microparticles entrapped with essential oils of varying viscosity

Double emulsion technique (W1/O/W2) was used to achieve PLA (polylactic acid)-based microparticles loaded with thymol (hydrophilic antibacterial active) with high encapsulation efficiency (> 90%) that was later released in water in controlled fashion. In order to enhance the release of thymol from semicrystalline slow degrading PLA matrix, pores were introduced into the particles by incorporating minute quantity of essential oils (EOs) such as castor, mustard, olive and coconut oils of varying viscosity (from 128 to 13 mPa S). Strikingly, it was found that the pore size of microparticles (pore size 1.2–0.53 µm and specific surface area 7.5–2.1 m2/g) has been influenced by the viscosity of EOs. The plausible mechanism of formation of pores using EOs was also explored. As expected, the release rate of thymol did get accelerate with the increase in pore density and its release mechanism can well be explained with the help of power law model. In addition to that, these porous particles were demonstrated to act as an effective carrier for continuous delivery of thymol with enhanced inhibitory activity probably due to synergistic action of EOs and thymol. Therefore, EOs employed here served dual purposes. These PLA-based microparticles composed of completely natural ingredients can be exploited as active food packaging material to prolong the shelf life of food.

Poly(ethylene carbonate)-containing polylactic acid microparticles with rifampicin improve drug delivery to macrophages.

Pulmonary delivery of antibiotics will decrease the required dose for efficient treatment of lung infections and reduce systemic side effects of the drug. The objective was to evaluate the applicability of poly(ethylene carbonate) (PEC) for the preparation of inhalable, antibiotic-containing particles. Rifampicin (RF)-loaded microparticles were prepared by electrospraying a carrier matrix of polylactic acid (PLA) with 0%, 5% and 10% PEC. Prepared particles had an aerodynamic diameter between 4 and 5μm. Within 60min, PEC-containing particles released 35-45% of RF, whereas PLA particles released only 15% of RF. Irrespective of particle composition, uptake of RF by macrophages was improved to 40-60% when formulated in microparticles compared to 0.4% for RF in solution, and intracellular localisation of particles was confirmed using confocal microscopy. Effect on macrophage and alveolar cell viability was similar for all particles whereas the minimal inhibitory concentrations against Pseudomonas aeruginosa and Escherichia coli for RF-containing PEC particles were twofold lower than for PLA particles, explained by the faster release of RF from PEC-containing particles. The inclusion of PEC in PLA microparticles increased the release of RF and the inhibitory effect against two bacteria species while displaying physical particle properties similar to PLA particles.

Interleukin-1β-Targeted Vaccine Improves Glucose Control and β-Cell Function in a Diabetic KK-Ay Mouse Model.

Interleukin-1β (IL-1β) has been implicated as a key proinflammatory cytokine involved in the pancreatic islet inflammation of type 2 diabetes mellitus (T2DM). Excess IL-1β impairs islet function by inducing insulin resistance and β-cell apoptosis. Therefore, specifically reducing IL-1β activity provides a therapeutic improvement for T2DM by sustaining the inhibition of IL-1β-mediated islet inflammation. In this study, we developed an IL-1β-targeted epitope peptide vaccine adjuvanted with polylactic acid microparticles (1βEPP) and applied it to a diabetic KK-Ay mouse model. Results showed that the 1βEPP elicited high antibody responses, which neutralized the biological activity of IL-1β, and induced barely detectable inflammatory activity. 1βEPP immunization reduced body weight gain, protected KK-Ay mice from hyperglycemia, improved glucose tolerance and insulin sensitivity, and decreased the serum levels of free fatty acids, total cholesterol and triglyceride. Moreover, 1βEPP restored β-cell mass; inhibited β-cell apoptosis; decreased the expression of IL-1β; and interrupted NF-κB activation by reducing IKKβ and pRelA levels. These studies indicated that the IL-1β-targeted vaccine may be a promising immunotherapeutic for T2DM treatment.

Polylactic acid and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) nano and microparticles for packaging bioplastic composites

Two methods, nanoprecipitation and emulsification/solvent evaporation with different solvents, to prepare nano and microparticles of polylactic acid (PLA) and PHBV are investigated. The obtained particles are characterized in terms of morphology by SEM and thermal properties by DSC and TGA. The objective is the preparation of PLA and PHBV nano and microparticles, with controlled shape and size distribution, for their further inclusion into biopolymer matrices such as PLA, PHBV or thermoplastic starch matrices. The purpose is the use of these biocomposites in the sector of wrapping and packaging. Good thermal properties of the nano and microparticles are important to the posterior processing as extrusion film technique. Although the smallest particles are obtained for PLA using nanoprecipitation technique with THF as solvent, these nanoparticles show a low thermal stability. The emulsification technique using dichloromethane as solvent shows to be a good option to obtain, for PLA and PHBV, spherical particles with controlled size and adequate thermal stability. The reproducibility of the selected method is studied for up-scaling nano and microparticle production to pre-industrial level. This study of reproducibility using statistical analysis shows the robustness of the methodology.

Immunopotentiation of Hepatitis B Vaccine Using Biodegradable Polymers as an Adjuvant

The purpose of this research was to develop an alternative adjuvant for hepatitis B vaccine (HBsAg) that elicits a long-lasting immune response after a single administration. In this study, the suitability of Poly (D, L)-lactide-co-glycolic acid (PLGA), Poly lactic acid (PLA) and Chitosan polymers as adjuvants for HBsAg were investigated. We used solvent evaporation and emulsion cross-linking techniques to encapsulate HBsAg into the different polymeric systems. The newly developed microparticles were evaluated for vaccine content, particle size distribution, in vitro release and immunogenicity. HBsAg-encapsulated PLGA and PLA microparticles were smooth and spherical. However, Chitosan microparticles were homogeneous, and almost spherical, with rough surfaces. The vaccine loading and release patterns varied with the type of polymer used. In this study, Chitosan polymeric microparticles released antigen until day 63 post-injection; however, the release period of the PLGA and PLA systems was shorter. A significant increase in the level of antibodies to HBsAg was induced by all the polymeric microparticles. The results indicate that Chitosan microparticles are a more efficient adjuvant for HBsAg than PLGA and PLA polymeric microparticles.

Use of polylactic acid for the preparation of microparticulate drug delivery systems.

This report reviews the development of particulate drug delivery systems technology based on polylactic acid (PLA). The following methods used to produce PLA microparticles are considered: emulsion solvent evaporation, emulsion solvent extraction, interfacial phase deposition, spray coating, and the melting method. The different preparation processes and parameters used, the characteristics of microparticles obtained and those parameters affecting the characteristics of these systems, are discussed.

A new method for the preparation of drug containing polylactic acid microparticles without using organic solvents

Microparticles of d,l-polylactic acid (PLA) prepared by a new method (melting method) were compared with microparticles obtained by the solvent evaporation/extraction method. For particle preparation by the melting method, the matrix polymer ( d,l-PLA, MW2000 or 16000) was melted in presence of the drug vinpocetine, a new neurotropic agent, to obtain a homogeneous mixture. After emulsification of the melt in a hot aqueous solution, microparticles were isolated by either pouring the hot emulsion into ice-water or spray drying, electron microscopy revealed a smooth surface of the d,l-PLA 2000 particles isolated by spray drying, whereas d,l-PLA 16000 microparticles and d,l-PLA 2000 isolated by centrifugation showed a rough surface. The mean diameter ranged from 2 to 22 μm, depending on the MW of the polymer and the isolation method. A faster drug release could be achieved by increasing the drug content or by addition of polyethylene glycol to d,l-PLA. These two factors are useful for influencing the release characteristics. For oral application an ideal retardation could be achieved with d,l-PLA 2000, whereas d,l-PLA 16000 microparticles showed a prolonged release characteristic over some days and should therefore be useful for intramuscular and subcutaneous administration. During the preparation of microparticles by melting, the MW was reduced by ca. 12%, as ascertained by end group titration. HPLC analysis demonstrated that the drug was stable during the preparation process.