Polycaprolactone Microparticles Research Articles

Smart wireless flexible bandage containing drug loaded polycaprolactone microparticles for real-time monitoring and treatment of chronic wounds.

The quality of life is negatively impacted by chronic wounds for more than 25 million people in the US. They are quite prone to infection, which may lead to the eventual loss of a limb. By exposing the ulcers to treatment agents at the appropriate time, the healing rate is increased. On-demand drug release in a closed-loop system will aid us in reaching our goal. In this study, we have developed a platform capable of real-time diagnosis of bacterial infection by wirelessly reading wound pH, as well as slow and on-demand local administration of antibiotics. The drug carrier microparticles, an electrical patch, a thermoresponsive hydrogel with an integrated microheater, and a flexible pH sensor comprised the closed-loop patch. Here it is reported that slow and smart release of cefazolin can be addressed by incorporation of drug encapsulated hydrophobic microparticles embedded into a thermo-responsive hydrogel. The utilization of a programmable bandage to provide antibiotic medication highlights the need of not only choosing appropriate therapeutic substances but also the controlled release of the medicine and its rate of release within the wound area. The results of our study indicate that the use of cefazolin encapsulated polycaprolactone (PCL) microparticles can effectively regulate the application of antibiotic treatment for chronic skin wounds. The results also showed a substantial gradual release of cefazolin from the thermo-responsive Pnipam hydrogel when the wound dressing was subjected to a temperature of 37°C. We believe that the developed flexible smart bandage can have a significant impact on chronic wound healing.

Acoustofluidic separation of bacteria from platelets using tilted-angle standing surface acoustic wave

Separation of microscale objects, such as cells and bacteria, is an essential sample preparation step in various microfluidic applications in microbiology, chemistry, biology, and biomedicine. Microfluidic separation of bacteria from blood cells is highly in demand to prevent or investigate bacterial infectious diseases. Unlike red and white blood cells, platelets have a similar size distribution to that of bacteria, which makes bacteria separation from platelets technically challenging. Most previous techniques for microfluidic separation rely on size as a separation marker. These size-based separation methods are not applicable to separation of the same or similar-sized samples. Here, we propose an acoustofluidic method using tilted-angle standing surface acoustic wave (taSSAW) for label-free separation of the microscale objects of the same or similar size based on compressibility. From the experimental investigation with polymethylmethacrylate, polystyrene, and polycaprolactone microparticles of the same size, we found that less compressible objects migrated further when exposed to the taSSAW field formed within a microchannel. Based on the findings, we demonstrated that Escherichia coli (E. coli) can be separated from platelets because the taSSAW-induced acoustic radiation force acting on comparatively less compressible E. coli was greater than that applied to the platelets. Fluorescence microscopy, scanning electron microscope, hemocytometry, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and polymerase chain reaction were conducted to confirm the successful positive separation of bacteria from platelets with high purity of exceeding 96 % and recovery rate of exceeding 81 %.

Liquefied capsules containing nanogrooved microdiscs and umbilical cord-derived cells for bone tissue engineering

Background Surface topography has been shown to influence cell behavior and direct stromal cell differentiation into distinct lineages. Whereas this phenomenon has been verified in two-dimensional cultures, there is an urgent need for a thorough investigation of topography’s role within a three-dimensional (3D) environment, as it better replicates the natural cellular environment. Methods A co-culture of Wharton’s jelly-derived mesenchymal stem/stromal cells (WJ-MSCs) and human umbilical vein endothelial cells (HUVECs) was encapsulated in a 3D system consisting of a permselective liquefied environment containing freely dispersed spherical microparticles (spheres) or nanogrooved microdiscs (microdiscs). Microdiscs presenting 358 ± 23 nm grooves and 944 ± 49 nm ridges were produced via nanoimprinting of spherical polycaprolactone microparticles between water-soluble polyvinyl alcohol counter molds of nanogrooved templates. Spheres and microdiscs were cultured in vitro with umbilical cord-derived cells in a basal or osteogenic medium within liquefied capsules for 21 days. Results WJ-MSCs and HUVECs were successfully encapsulated within liquefied capsules containing spheres and microdiscs, ensuring high cellular viability. Results show an enhanced osteogenic differentiation in microdiscs compared to spheres, even in basal medium, evidenced by alkaline phosphatase activity and osteopontin expression. Conclusions This work suggests that the topographical features present in microdiscs induce the osteogenic differentiation of adhered WJ-MSCs along the contact guidance, without additional differentiation factors. The developed 3D bioencapsulation system comprising topographical features might be suitable for bone tissue engineering approaches with minimum in vitro manipulation.

Polycaprolactone microparticles for the subcutaneous administration of cannabidiol: in vitro and in vivo release.

Cannabidiol (CBD) has become a highly attractive entity in therapeutics. However, its low aqueous solubility, instability and handling problems limit the development of effective CBD formulations. Subcutaneously administered CBD-loaded polycaprolactone microparticles (MP) represent an interesting strategy to overcome these challenges. This work focuses on evaluating the pharmacokinetics of CBD formulated in polymer microparticles for subcutaneous administration and characterising its release. The mean release time (MRLT) parameter is used to compare the release of CBD from two microparticle formulations in vitro and in a mouse model. After the administration of CBD in solution, a bicompartmental distribution is observed due to the extensive diffusion to the brain, being the brain/blood AUC ratio 1.29. The blood and brain mean residence time (MRT) are 0.507 ± 0.04 and 0.257 ± 0.0004days, respectively. MP prepared with two drug/polymer ratios (15/150-MP and 30/150-MP) are designed, showing similar in vitro dissolution profiles (similarity factor (f2) is 63.21), without statistically significant differences between MRLTin vitro values (4.68 ± 0.63 and 4.32 ± 0.05days). However, considerable differences in blood and brain profiles between both formulations are detected. The blood and brain MRT values of 15/150-MP are 6.44 ± 0.3days and 6.15 ± 0.25days, respectively, whereas significantly lower values 3.91 ± 0.29days and 2.24 ± 0.64days are obtained with 30/150-MP. The extended release of CBD during 10days after a single subcutaneous administration is achieved.

Preparation, characterization and biocompatibility of calcium peroxide-loaded polycaprolactone microparticles.

To explore the physicochemical characteristics and biocompatibility of calcium peroxide (CPO)-loaded polycaprolactone (PCL) microparticle. The CPO/PCL particles were prepared. The morphology and elemental distribution of CPO, PCL and CPO/PCL particles were observed with scanning electron microscopy and energy dispersive spectroscopy, respectively. Rat adipose mesenchymal stem cells were isolated and treated with different concentrations (0.10%, 0.25%, 0.50%, 1.00%) of CPO or CPO/PCL particles. The mesenchymal stem cells were cultured in normal media or osteogenic differentiation media under the hypoxia/normoxia conditions, and the amount of released O2 and H2O2 after CPO/PCL treatment were detected. The gene expressions of alkaline phosphatase (ALP), Runt-associated transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) were detected by realtime RT-PCR. SD rats were subcutaneously injected with 1.00% CPO/PCL particles and the pathological changes and infiltration of immune cells were observed with HE staining and immunohistochemistry at day 7 and day 14 after injection. Scanning electron microscope showed that CPO particles had a polygonal structure, PCL particles were in a small spherical plastic particle state, and CPO/PCL particles had a block-like crystal structure. Energy dispersive spectroscopy revealed that PCL particles showed no calcium mapping, while CPO/PCL particles showed obvious and uniform calcium mapping. The concentrations of O2 and H2O2 released by CPO/PCL particles were lower than those of CPO group, and the oxygen release time was longer. The expressions of Alp, Runx2, Ocn and Opn increased with the higher content of CPO/PCL particles under hypoxia in osteogenic differentiation culture and normal culture, and the induction was more obvious under osteogenic differentiation conditions (all P<0.05). HE staining results showed that the muscle tissue fibers around the injection site were scattered and disorderly distributed, with varying sizes and thicknesses at day 7 after particle injection. Significant vascular congestion, widened gaps, mild interstitial congestion, local edema, inflammatory cell infiltration, and large area vacuolization were observed in some tissues of rats. At day 14 after microparticle injection, the muscle tissue around the injection site and the tissue fibers at the microparticle implantation site were arranged neatly, and the gap size was not thickened, the vascular congestion, local inflammatory cell infiltration, and vacuolization were significantly improved compared with those at day 7. The immunohistochemical staining results showed that the expressions of CD3 and CD68 positive cells significantly increased in the surrounding muscle tissue, and were densely distributed in a large area at day 7 after particle injection. At day 14 of microparticle injection, the numbers of CD3 and CD68 positive cells in peripheral muscle tissue and tissue at the site of particle implantation were lower than those at day 7 (all P<0.01). CPO/PCL particles have good oxygen release activity, low damage to tissue, and excellent biocompatibility.

Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side effects. Here, we aimed at designing new negative temperature-responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan-β-glycerophosphate-based thermogel (THG)-containing mesoporous SiO2 nanoparticles (THG@SiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2-TMZ and THG@PCL-TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ-silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2-TMZ) and TMZ, spray-dried on PLC and incorporated into the thermogel (THG@PCL-TMZ), induced cell death in vitro. When applied intracranially to a resected U87-MG-Red-FLuc human GBM model, THG@SiO2-TMZ and THG@PCL-TMZ caused a significant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2-TMZ and THG@PCL-TMZ are therefore new promising gel-based local therapy candidates for the treatment of GBM.

Mechanism and kinetics of enzymatic degradation of polyester microparticles using a shrinking particle-shrinking core model.

Generalized shrinking particle (SPM) and shrinking core (SCM) models were developed to the kinetics of heterogenous enzymatic degradation of polymer microparticles in a continuous microflow system. This enzymatic degradation was performed in a microfluidic device designed to both physically separate and immobilize the microparticles. Then time-resolved measurements were made using image processing of the physical changes of the particles during degradation. The kinetics of enzyme-polymer intermediate formation, enzymatic bond cleavage, and enzyme diffusion through the layer of degraded substrate (SCM only) were mathematically derived to predict the time-resolved degradation of the substrate. The proposed models were tested against the degradation of 15-25 μm particles of polycaprolactone (PCL) and poly (butylene adipate-co-terephthalate) (PBAT) by cutinase enzyme from Humicola insolens. Degradation of PCL microparticles followed the SPM model and its kinetics were found to be zero-order, while the SCM model applied to PBAT microparticles showed first-order kinetics. Further, the degradation of polybutylene succinate (PBS), and poly butylene-sebacate-co-terephthalate (PBSeT) microparticles demonstrated wide applicability of the method. The use of image processing simplifies the required analysis by eliminating the need to remove aliquots or concentrate effluent for additional analytical characterization.

Removal of Hydrophobic Organic Pollutants and Copper by Alginate-Based and Polycaprolactone Materials

Organic pollutants (OPs) and heavy metals are environmental toxicants associated with great concerns. Decontamination processes are urgent for both, and the possibility to achieve their simultaneous removal from polluted waters is highly interesting. Additionally, in many cases, the effect of organic matter in the removal process is overlooked and must be considered. This work aimed to study the potential of alginate-based and polycaprolactone (PCL) materials to remove OPs and copper ions in the absence and presence of organic matter. The OPs investigated were the polycyclic aromatic hydrocarbons anthracene and benzo[a]pyrene, and the pesticide chlorpyrifos, both hydrophobic compounds. Copper (II) ions were used as a model of heavy metals. Alginate-based spheres were prepared by gelation, and PCL microparticles were obtained by oil/water emulsion solvent evaporation. The materials with the highest efficiencies for OP removal from aqueous solutions were those with activated carbon and PCL. Furthermore, the spheres with activated carbon could remove anthracene and copper simultaneously, even in the presence of humic acid. This work points to activated carbon–alginate spheres as a multifunctional adsorbent able to remove different pollutants and to PCL for potential applications in OP decontamination processes.

Bilayer fixed-dose combination tablet for curcumin microparticles and piroxicam and in vitro evaluation.

Aim: In the present work, fixed-dose combination of bilayer tablets for piroxicam as and curcumin as immediate-release and sustained-release layer (SRL) respectively for management of inflammatory response. Materials & methods: The SRL include Curcumin polycaprolactone microparticles from spray drying. The tablet layers include Pearlitol 200SD, Microcrystalline cellulose PH101, Aerosil 200, talc each layer. Results: SEM studies confirm spherical microparticles. PXRD and DSC studies confirm the amorphous microparticles. In vitro studies exhibit, an immediate release and sustained release for Piroxicam and Curcumin after 2 h. Cellular uptake studies on RAW 264.7cells confirm the complete internalization of microparticles. Conclusion: Therefore, it was concluded that microparticles can be formulated into a unit dosage form for the management of inflammation.

Microfluidic Generation of Therapeutically Relevant Polycaprolactone (PCL) Microparticles: Computational and Experimental Approaches

Drug releasing microparticles play an important role in drug delivery as they can be used for site specific delivery as well as control over the release time of therapeutics. The use of microfluidic technologies for the fabrication of these particles is of increasing interest since they provide enhanced control over microparticle size and size distribution compared to bulk production methods. However, the use of microfluidic platforms in the production of drug releasing microparticles with therapeutically relevant cargo still requires optimization depending on their application, and the effect of the addition of cargo on the production process is still unexplored. Here we show the formation of therapeutically relevant (in terms of size and dose of cargo) polycaprolactone (PCL) microparticles using a microfluidic platform and analyze the effect of the addition of cargo in the microparticle size and size distribution. This microfluidic platform was designed with the aid of computational fluid dynamic simulations, allowing us to construct a polydimethylsiloxane (PDMS) microfluidic device capable of making microparticles in the range of 15 to 35 μm with low coefficient of variation (CV) both with and without cargo by varying the flow rate ratios of the phases used during droplet generation. Our data show the effect of the addition of cargo on the droplet and microparticle sizes and monodispersity. Our fabrication method allows the formation of spherical microparticles, optimal for biomedical applications. In addition, our microfluidic platform can maintain the generation of monodisperse droplets (with an average size of 52.5 μm) over extended periods of time, suggesting it has the capacity to be used for scaled-up production of PCL microparticles. This microfluidic device is a robust and reliable method for the fabrication of PCL microparticles with cargo, which can potentially be loaded with other relevant therapeutic molecules for biomedical applications.

THE ELECTROSPRAYED INSULIN-LOADED POLYCAPROLACTONE MICROPARTICLES AS A DRUG CARRIER

Drug and protein encapsulated polymeric microparticles have been considered as the most effective delivery in pharmaceutical biotechnology. In this work, we report the fabrication of polycaprolactone microparticles (PCL MPs) containing insulin via an electrospraying method. The morphology, chemical composition, physicochemical properties, insulin encapsulation and release efficiency, degradation of PCL MPs, and cytotoxicity are systematically characterized and analyzed. The results indicate that insulin do not incorporate with PCL matrix leading to the deformation of PCL MPs’ structure. In addition, insulin can be loaded into the PCL MPs with high concentration up to 25 % while it remains chemical properties when releasing from the PCL MPs. Moreover, insulin demonstrates high burst release within the first day, subsequently the release become more stable during 2-7 days. The 80% viability of the cell suggests that PCL MPs are biocompartible to cells. As a consequence, the above mentioned material is proved to be has high potential for insulin carrier in controlled release application

Flow Dispersion for Obtaining Ivermectin Encapsulated in Polycaprolactone Microparticles

Introduction. Ivermectin is an antiparasitic drug that has been widely used in veterinary medicine. Parasitic diseases of farm animals cause great economic damage and pose the risk of human infection. Prolonged dosage forms of ivermectin are effective against them. The first step in the creation of such a drug was the preparation and study of polymeric microparticles of polycaprolactone with encapsulated ivermectin. Aim. Obtaining polymeric microparticles of polycaprolactone with encapsulated ivermectin using a continuous flow-through unit. Materials and methods. The object of the study was microparticles of polycaprolactone with encapsulated ivermectin obtained on a continuous flow-through unit. Determination of the average particle size and size distribution was carried out by the method of laser diffraction. Microscopy was used to visually assess the shape and size of the microparticles. UV – spectrophotometry was use to quantitative determination of ivermectin. Results and discussion. Polymeric microparticles of polycaprolactone with encapsulated ivermectin was obtained and had an average size of 126.63 ± 42.67 μm and contained 32,73–62,00 % of ivermectin. Suspensions prepared from the obtained microparticles were passed through a 20G injection needle without noticeable resistance, which indicates the possibility of their use as the basis of an injectable preparation. Conclusion. Obtained results confirm the possibility of using flow-through dispersion using a device developed by us for obtaining polycaprolactone microparticles with encapsulated ivermectin, which are suitable for injection. Thus, the results obtained make it possible to continue studies of microparticles and create a drug based on them.

The effect of solvent and pressure on polycaprolactone solutions for particle and fibre formation

Polycaprolactone (PCL) is a widely used material in many applications to tackle health problems worldwide. Formed micro- or nanosized PCL particles and fibres benefit from a higher surface area to volume ratio and are valuable in those applications, thus there is always a push to achieve smaller diameters. Electrohydrodynamic (EHD) technologies have been at the forefront in the production of polymeric biomaterials, and pressurised gyration (PG) has also enhanced possibilities by its ability to spin comparable fibres at rapid speeds. In this work, PCL microparticles and fibres were separately produced by changing key operating parameters of EHD and PG systems and PCL solution properties. Initially, PCL microparticles were formed by electrospraying with different binary solvent systems, followed by pressurised gyration fibre production with various singular solvents and a pre-optimised binary solvent system. As anticipated, the use of binary systems altered particle morphologies and diameters, while increased pressure and the use of different solvents greatly affected the characteristics of resulting fibres. The morphology of PCL was found to be highly dependent on the solvents and operating parameters of the technology used.

Quantitative Determination of Ivermectin in Polymer Microspheres

Introduction. Ivermectin is known as a veterinary agent with a wide spectrum of action against endo-and exoparasites of farm animals, which makes its use promising. Therefore, the possibility of creating prolonged parenteral dosage forms using polymer biodegradable carriers is currently being investigated. To carry out their quality control, a method of quantitative determination of the active substance is necessary. Most of the previously proposed methods are characterized by time-consuming sample preparation, complex composition of the mobile phase or a long analysis time, therefore, during the development of an injectable prolonged preparation of ivermectin based on polycaprolactone microparticles, a new method for the quantitative determination of ivermectin was proposed, which is simple and suitable for use in production.Aim. Development of a method for the quantitative determination of ivermectin in the composition of polycaprolactone microparticles and its validation.Materials and methods. Microparticles with ivermectin were used as the object of the study. The method of quantitative determination of ivermectin in the test sample was developed on a high-performance liquid chromatograph Dionex UltiMate 3000 (Thermo Fisher Scientific, USA), equipped with a diode-matrix detector.Results and discussion. In this paper, various conditions for the quantitative determination of ivermectin in the composition of polymer microparticles are studied. Based on the obtained data and results, a method has been developed that has optimal sample preparation and analysis conditions.Conclusion. As a result of the development, the conditions for the analysis were selected, which allow us to evaluate the quantitative content of ivermectin in the sample. The method was validated for the parameters specificity, analytical area, linearity, trueness, repeatability, intermediate precision.

Robust and scalable production of emulsion-templated microparticles in 3D-printed milli-fluidic device

Emulsions are ideal templates for preparation of functional microparticles in food, cosmetics, and pharmaceutics. However, the lack of a simple and robust platform that allows mass production of oil-in-water (O/W) emulsions has been considered as a practical hurdle for broader applicability of these emulsion-based technologies. Herein, we report a novel 3D-printed milli-fluidic device (3D-PMD) for robust and scalable production of water-in-oil (W/O) as well as O/W emulsions. By using an additive manufacturing method with one-step prototyping capability, 3D-PMD integrates an array of 40 drop-makers with a 3D void geometry and a flow distributor in a compact fashion, which has been difficult to achieve using conventional methods. Experimental results as well as the computational fluid dynamics simulation confirm the validity in the design of the drop-maker and the flow distributor, as well as the hydrophilic surface modification process for the robust and controllable production of poly(ethylene glycol) microgels and polycaprolactone microparticles, prepared from W/O and O/W emulsions, respectively. We anticipate that the simplicity, low-cost ($150/per device), facile manufacturability, and versatile emulsion production capability of our 3D-PMD method offers a unique route to produce W/O and O/W emulsions in a robust and in a scalable manner, providing new and exciting opportunities in various applications involving functional microparticles such as cosmetic products, optical displays, controlled reactions, and drug delivery systems to name a few.

Design of Protein-Based Liquefied Cell-Laden Capsules with Bioinspired Adhesion for Tissue Engineering.

Platforms with liquid cores are extensively explored as cell delivery vehicles for cell-based therapies and tissue engineering. However, the recurrence of synthetic materials can impair its translation into the clinic. Inspired by the adhesive proteins secreted by mussels, liquefied capsule is developed using gelatin modified with hydroxypyridinones (Gel-HOPO), a catechol analogue with oxidant-resistant properties. The protein-based liquefied macrocapsule permitted the compartmentalization of living cells by an approachable and non-time-consuming methodology resorting to i) superhydrophobic surfaces as a processing platform of hydrogel beads, ii) gelation of gelatin at temperatures <25°C, iii) iron coordination of the hydroxypyridinone (HOPO) moieties at physiological pH, and iv) core liquefaction at 37 °C. With the design of a proteolytically degradable shell, the possibility of encapsulating human adipose-derived mesenchymal stem cells (hASC) with and without the presence of polycaprolactone microparticles (μPCL) is evaluated. Showing prevalence toward adhesion to the inner shell wall, hASC formed a monolayer evidencing the biocompatibility and adequate mechanical properties of these platforms for proliferation, diminishing the need for μPCL as a supporting substrate. This new protein-based liquefied platform can provide biofactories devices of both fundamental and practical importance for tissue engineering and regenerative medicine or in other biotechnology fields.

Chitosan/PCL nanoparticles can improve anti-neoplastic activity of 5-fluorouracil in head and neck cancer through autophagy activation.

Head and neck squamous cell carcinoma (HNSCC), a prevalent cancer worldwide, has a high incidence of loco-regional dissemination, frequent recurrence, and lower 5-year survival rates. Current gold standard treatments for advanced HNSCC rely primarily on radiotherapy and chemotherapy but with limited efficacy and significant side effects. In this study, we characterized a novel 5-fluorouracil (5-FU) carrier composed of chitosan solution (CS) and polycaprolactone (PCL) microparticles (MPs) in HNSCC preclinical models. The designed MPs were evaluated for their size, morphology, drug entrapment efficiency (EE%) and in vitro drug release profile. The anti-cancer activity of 5-FU-loaded particles was assessed in HNSCC human cell lines (CAL27 and HSC3) and in a preclinical mouse model (AT84) utilizing cell proliferation and survival, cell motility, and autophagy endpoints. The results demonstrated a 38.57 % in 5-FU entrapment efficiency associated with reduced 5-FU in vitro release up to 96 h post-exposure. Furthermore, CS-decorated PCL MPs were able to promote a significant inhibition of cancer cell proliferation based on the metabolic and colony formation assays, in comparison to controls. In contrast, CS-decorated PCL MPs did not influence the pharmacological efficacy of 5-FU to inhibit in vitro cancer cell migration. Last, cell protein analysis revealed a significant increase of autophagy and cell death evaluated by LC3-II expression and PARP1 cleavage, respectively. In summary, these results support the potential utility of CS-decorated PCL MPs as an effective 5-FU-delivery carrier to improve HNSCC therapeutic management.

Magnetically Responsive Polymeric Microparticles for the Triggered Delivery of a Complex Mixture of Human Placental Proteins.

Bone loss through traumatic injury is a significant clinical issue. Researchers have created many scaffold types to mimic an extracellular matrix to provide structural support for the formation of new bone, however functional regeneration of larger scaffolds has not been fully achieved. Newer scaffolds aim to deliver bioactive molecules to improve tissue regeneration. To achieve a more comprehensive regenerative response, a magnetically triggerable polymeric microparticle platform is developed for the on-demand release of a complex mixture of isolated human placental proteins. This system is composed of polycaprolactone (PCL) microparticles, encapsulating magnetic nanoparticles (MNPs), and placental proteins. When subjected to an alternating magnetic field (AMF), the MNPs heat and melt the PCL, enhancing the diffusion of proteins from microparticles. When the field is off, the PCL re-solidifies. This potentially allows for cyclic drug delivery. Here the design, synthesis, and proof-of-concept experiments for this system are reported. In addition, it is shown that the proteins retain function after being magnetically released. The ability to trigger the release of complex protein mixtures on-demand may provide a significant advantage with wounds where stagnation of healing processes can occur (e.g., large segmented bone defects).

Antioxidants entrapment in polycaprolactone microparticles using supercritical assisted injection in a liquid antisolvent

In this work, the entrapment of two antioxidants, α-lipoic acid (ALA) and eugenol (EUG), in polycaprolactone (PCL) microparticles, using the supercritical assisted injection in a liquid antisolvent (SAILA), is proposed.Using SAILA, spherical and non-aggregated PCL particles, with average sizes between 0.2 and 1.2 μm, were produced. Then, coprecipitation experiments were performed: PCL/EUG and PCL/ALA particles with an average size of 0.99 ± 0.34 μm and 0.99 ± 0.18 μm, respectively, were produced, with entrapment efficiencies up to 90 %, considerably higher than results reported in the literature. EUG and ALA coprecipitates showed complete release kinetics in a maximum time of 2 days respect to dissolution time of about 4 h and 5 h of unprocessed EUG and ALA, respectively. Furthermore, the antioxidant power of the used compounds was preserved in the obtained co-precipitates.

Effects of the electrosprayed polycaprolactone microparticles morphology on the polycaprolactone degradation

The polycaprolactone (PCL) microparticles fabricated by electrospray technique have been studied and applied in drug and protein delivery system. The degradation of PCL and the release of drug/protein from the polymeric microparticles (MPs) were desired to happen simultaneously. When the new dosage was administrated, the PCL MPs were degraded and eliminated out of the body. This research indicated that the degradation of PCL was influenced by the various morphology of electrosprayed microparticles. The different sizes of 11.8 μm and 5.17 μm and the various shapes of the PCL MPs such as hollow, porous and wrinkle particles and spheres were investigated the PCL degradation in the PBS solution, at pH 7.4. The morphology of PCL MPs was designed by controlling the polymer solution and the electrosprayed processing parameters such as the flow rate and collecting distance. Scanning electron microscopy and gel permeation chromatography were order to determine the change of the morphology and number molecule weight (Mn) of PCL MPs. The porous, distorted and smaller particles reduced the Mn faster than the microspheres because of the larger surface area of MPs contacted with PBS solution. After 77 days, PCL MPs which were fabricated by the processing parameter, including 2.5% PCL in DCM, flow rate of 0.8 mL/h, voltage of 18 kV, collecting distance of 25 cm, reduced 49.96% molecular weight (decreasing from Mn= 80,438 g/mol to 40,225 g/mol).&#x0D;