PCL Microspheres Research Articles

Injectable methotrexate loaded polycaprolactone microspheres: Physicochemical characterization, biocompatibility, and hemocompatibility evaluation

In this study, bare polycaprolactone microspheres (PCL MPs) and methotrexate (MTX) loaded PCL microspheres (MTX-PCL MPs) have been developed by oil-in-water emulsion solvent evaporation method using hydroxypropyl methylcellulose (HPMC) as an emulsifier. Encapsulation efficiency and loading capacity of methotrexate were found to be 51.28%±0.52 and 2.8%±0.06 respectively. Environmental scanning electron microscopy showed the PCL MPs and MTX-PCL MPs to have a spherical shape and smooth surface morphology. The mean size of microspheres (23μm) was found within injectability criteria. High-Resolution X-ray diffraction of microspheres revealed that PCL retained its semi-crystalline nature after processing in microspheres, but the drug looses its crystallinity. Fourier transmittance infrared spectroscopy and thermogravimetry analysis of the microspheres indicated that no physicochemical modification occurred. In vitro, MTX release study from MTX-PCL MPs in phosphate buffer saline (pH7.4) showed controlled release profile and only 31% of MTX released in 306h. The microspheres in lyophilized form are physicochemically stable for 8months. Furthermore, L929 cells treated with microspheres showed cell viability >80%. The different concentrations of microspheres found hemocompatible and did not affect the biconcave shape of red blood cells (RBCs). The physiochemical and biological evaluation of microspheres suggests their further use for drug delivery application.

Selective laser sintering scaffold with hierarchical architecture and gradient composition for osteochondral repair in rabbits.

Osteochondral defects cannot be adequately self-repaired due to the presence of the sophisticated hierarchical structure and the lack of blood supply in cartilage. Thus, one of the major challenges remaining in this field is the structural design of a biomimetic scaffold that satisfies the specific requirements for osteochondral repair. To address this hurdle, a bio-inspired multilayer osteochondral scaffold that consisted of the poly(ε-caprolactone) (PCL) and the hydroxyapatite (HA)/PCL microspheres, was constructed via selective laser sintering (SLS) technique. The SLS-derived scaffolds exhibited an excellent biocompatibility to support cell adhesion and proliferation invitro. The repair effect was evaluated by implanting the acellular multilayer scaffolds into osteochondral defects of a rabbit model. Our findings demonstrated that the multilayer scaffolds were able to induce articular cartilage formation by accelerating the early subchondral bone regeneration, and the newly formed tissues could well integrate with the native tissues. Consequently, the current study not only achieves osteochondral repair, but also suggests a promising strategy for the fabrication of bio-inspired multilayer scaffolds with well-designed architecture and gradient composition via SLS technique.

Interlaminar toughening of resin transfer molded laminates by electrospun polycaprolactone structures: Effect of the interleave morphology

Today, fiber reinforced polymer composites are a standard material in applications where a high stiffness and strength are required at minimal weight. Although fiber reinforced polymer composites show many advantages compared to other materials, delamination between reinforcing plies remains a major problem limiting further breakthrough. Previous work has shown that electrospun nanofibers can significantly improve the interlaminar fracture toughness of fiber reinforced composites thus preventing delaminations. In the present paper, the effect of the morphology of the toughening polymer is analyzed by incorporating different polycaprolactone structures in the interlaminar regions. Both Mode I and Mode II interlaminar facture toughness of composites containing five different electrospun morphologies - nanofibers, microfibers, microspheres, dense films, and PCL spray coated glass fibers - were evaluated. Analyzing the fracture behavior of the PCL toughened laminates ensures a better insight in the micromechanical fracture mechanisms behind the observed interlaminar fracture toughness and results in guidelines on the optimal interleave morphology. The results clearly demonstrate the distribution of PCL in the interlayer has a large effect on the crack path of the delamination and the resulting interlaminar fracture toughness. In order to improve the interlaminar fracture toughness in both Mode I as well as Mode II without adverse effects, porous PCL structures such as PCL nanofibers, microfibers, and microspheres are much more suitable than non-porous structures such as PCL films or spray-coated glass fibers. Among the porous structures, the nanofibers had an overall better performance with an increase in Mode I and Mode II interlaminar fracture toughness of about 60% and 80% respectively.

Raloxifene-/raloxifene-poly(ethylene glycol) conjugate-loaded microspheres: A novel strategy for drug delivery to bone forming cells

Raloxifene (Ral)- or Ral-poly(ethylene glycol) (PEG) conjugate-loaded microspheres were prepared with poly(ε-caprolactone) (PCL) alone or with the blend of PCL and poly(D,L-lactide-co-glycolide) (PLGA) to provide controlled and sustained Ral release systems. Benefits of these formulations were evaluated on bone regeneration. Ral-loaded PCL microspheres had the highest encapsulation efficiency (70.7±5.0%) among all groups owing to high hydrophobic natures of both Ral and PCL. Cumulative amount of Ral released from Ral-PEG (1:2) conjugate-loaded PCL:PLGA (1:1) microspheres (26.9±8.8%) after 60days was significantly higher relative to other microsphere groups. This finding can be ascribed to two factors: i) Ral-PEG conjugation, resulting in increased water-solubility of Ral and increased degradation rates of PCL and PLGA with enhanced water penetration into the polymer matrix, and ii) usage of PLGA besides PCL in the carrier composition to benefit from less hydrophobic and faster degradable nature of PLGA in comparison to PCL. In vitro cytotoxicity studies performed using adipose-derived mesenchymal stem cells (ASCs) demonstrated that all microspheres were non-toxic. Evaluation of intensities of Alizarin red S staining conducted after 7 and 14days of incubation of ASCs in the release media of the different microsphere groups was performed with Image J analysis software. At day 7, it was observed that the matrix deposited by the cells cultivated in the release medium of Ral-PEG (1:2) conjugate-loaded PCL:PLGA (1:1) microspheres had significantly higher mineral content (26.78±6.23%) than that of the matrix deposited by the cells cultivated in the release media of the other microsphere groups except Ral-loaded PCL:PLGA (1:1) microsphere group. At day 14, Ral release from Ral-PEG (1:2) conjugate-loaded PCL:PLGA (1:1) microsphere group resulted with significantly higher mineralization of the matrix (32.31±1.85%) deposited by ASCs in comparison to all other microsphere groups. Alizarin red S staining results eventuated in parallel with the release results. Thus, it can be suggested that Ral-PEG (1:2) conjugate-loaded PCL:PLGA (1:1) microsphere formulation has a potential as an effective controlled drug delivery system for bone regeneration.

Magnetically responsive polycaprolactone nanoparticles for progesterone screening in biological and environmental samples using gas chromatography.

A new Fe3O4/poly(є-caprolactone) (PCL) magnetite nanocomposite was fabricated and used as a sorbent for magnetically mediated PCL microspheres solid-phase extraction (MM-PCL-SPE) followed by gas chromatography-flame ionization detection (GC-FID) for monitoring of progesterone (PGN) hormone in biological and environmental matrices, namely blood serum, tap water, urine, and hospital wastewater. The nanomagnetite core of the sorbent was synthesized by a co-precipitation method. Magnetic nanoparticles (MNPs) were then microencapsulated with PCL microspheres using emulsion polymerization. The nanocomposite was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). The magnetite sorbent can be effectively dispersed in aqueous solution and attracted to an external magnetic field. The MM-PCL-SPE process for PGN assay involved (a) dispersion of the sorbent in the donor phase aqueous solution with sonication, (b) exposure to a magnetic field to collect sorbent that had adsorbed the analyte, and (c) solvent desorption of extracted PGN for GC-FID analysis. The work demonstrates the usefulness of MM-PCL-SPE in the rapid and sensitive monitoring of trace amounts of PGN in real samples. The limit of detection (LOD) and limit of quantification (LOQ) were 1.00 and 3.30ng/mL, respectively. The relative recoveries in real samples were adequate. Linearity was observed over a wide range of 2.2-10,000.0ng/mL in aqueous media and urine and 0.01-70.0μg/mL in blood serum. Graphical Abstract In this research new Fe3O4/poly(є-caprolactone) (PCL) magnetite microspheres were developed as an efficient sorbent for solid-phase extraction of progesterone hormone in biological and environmental matrices.

Biodegradable mesoporous bioactive glass nanospheres for drug delivery and bone tissue regeneration

Bioactive inorganic materials are attractive for hard tissue regeneration, and they are used as delivery vehicles for pharmaceutical molecules, scaffolds and components for bio-composites. We demonstrated mesoporous bioactive glass (BG) nanospheres that exhibited the capacity to deliver pharmaceutical molecules. Mesoporous BG nanospheres with variable Ca to Si ratios were synthesized using sol–gel chemistry. By controlling the hydrolysis and condensation conditions, the diameter of the mesoporous BG nanospheres was changed from 300 nm to 1500 nm. The porous structure and surface area of the BG nanospheres were shown to be dependent on their composition. The surface area of the BG nanospheres decreased from 400 ± 2 m2 g−1 to 56 ± 0.1 m2 g−1 when the Ca/Si ratio increased from 5 to 50 at.%. When the mesoporous BG nanospheres were loaded with ibuprofen (IBU), they exhibited a sustained release profile in simulated body fluid (SBF). In the meantime, the IBU-loaded BG nanospheres degraded in SBF, and induced apatite layer formation on the surface as a result of their good bioactivity. When the BG nanospheres were used as a composite filler to poly (ε-caprolactone) (PCL), they were shown to be effective at improving the in vitro bioactivity of PCL microspheres.

Cell-free fibrin scaffolds for in situ regeneration of full thickness cartilage defects

Event Abstract Back to Event Cell-free fibrin scaffolds for in situ regeneration of full thickness cartilage defects Changyou Gao1, Yuankun Dai1 and Lie Ma1 1 Zhejiang University, Department of Polymer Science and Engineering, China Introduction: Cartilage tissue engineering is a promising way to regenerate the damaged cartilage. Pre-loading of cells in the scaffolds is the usual way, but is less applicable in translation of the technique. In situ recruitment of bone marrow stem cells into the scaffolds would bypass the controversy and promote the medical translation of regenerative system[1]. Fibrinogen (Fg) has abundant bioactive domains[2]. Herein macro-porous fibrin scaffolds (FS) are prepared, and are applied without pre-seeding any cells for in situ regeneration of full thickness cartilage defects. Material and Methods: Evenly mixed PCL microspheres[3] and Fg powder were compressed in a mould to remove air, which was transformed into PCL/Fg cake at 65 oC for 1 h. 25 U thrombin was added to get a fibrin clot. The PCL microspheres were dissolved by acetone, which was exchanged with graded ethanol solution to obtain the FS after lyophilization. FS were transplanted into full thickness cartilage defects (4 mm in diameter, 4 mm in depth) in the center of the patella groove of rabbits. Results and Discussion: Highly interconnected pores were found in FS with porosity higher than 80%. The compressive modulus of hydrated FS was about 5 kPa. 50% mass loss of the FS after 40 days’ culture in DMEM with 10% FBS would support the cell proliferation and extracellular matrix deposition. BMSCs showed an accumulation morphology and proliferation behavior in FS. 12 weeks after in vivo regeneration, the defects were filled with neo tissue with smooth surface and well integrity with surrounding tissue. Histological analysis confirmed the deposition of cartilage components. Expression of cartilage relative genes and proteins in the neo tissue was higher than those of native cartilage. All these results prove the regeneration of cartilage with the assistance of FS. Conclusion: In vivo neo cartilage could be formed after transplantation of the cell-free FS, showing higher expression of cartilage relative genes and proteins. The in situ cartilage regeneration using the cell-free FS gives an insight into the in situ tissue regeneration by evoking the instinctive pro-healing behavior. The Natural Science Foundation of China (21434006, 21374097, and 51322302)

Directed differentiation of human induced pluripotent stem cells into neuronal subtypes by small molecule releasing microspheres

Event Abstract Back to Event Directed differentiation of human induced pluripotent stem cells into neuronal subtypes by small molecule releasing microspheres Andrew M. Agbay1, Laura De La Vega Reyes2, Jose C. Gomez3 and Stephanie M. Willerth1, 3 1 University of Victoria, Division of Medical Sciences, Canada 2 Tecnológico de Monterrey, Campus Guadalajara, Division of Architecture,Engineering and Health sciences, Mexico 3 Univeristy of Victoria, Mechanical Engineering, Canada Introduction: Previous microsphere research has demonstrated the potential of microsphere-based drug delivery for directing the differentiation of human induced pluripotent stem cells (hiPSCs) for neural tissue engineering applications[1]. Cell replacement therapies using hiPSCs are ideal for conditions where patients experience loss or damage of neurons such as in Parkinson’s disease (dopaminergic neurons) (DNs) and spinal cord injury (motor neurons) (MNs)[2]. The steroid guggulsterone has been shown to efficiently derive DNs from hiPSCs[3] while MNs can be derived from a combination of the small molecules retinoic acid (RA) and purmorphamine[4]. The aim of this study is to produce guggulsterone and purmorphamine encapsulated poly(Ɛ-caprolactone) (PCL) microspheres and then incorporate these drug releasing microspheres into hiPSC aggregates where they can promote the differentiation of hiPSCs into different neuronal subtypes. Materials and Methods: A water-in-oil emulsion was used to fabricate the microspheres. Encapsulation efficiencies were calculated by measuring light absorbance of the extracted drug at 240 nm for guggulsterone and 319 nm for purmorphamine. In vitro drug release studies over 44 and 28 days were done in triplicate. Guggulsterone microspheres will be incorporated with neural aggregates to induce differentiation into DNs while a mixture of previously encapsulated RA microspheres[1] and purmorphamine microspheres will be incorporated to generate MNs. For incorporation of microspheres into neural aggregates, appropriate combinations of microspheres will be added to hiPSC suspensions and centrifuged into AggreWellTM800 inserts (STEMCELL Technologies). The resulting differentiation will be determined by flow cytometry to detect viability, pluripotency, and neuronal marker expression while immunocytochemistry will be used to visualize the resulting differentiation. Finally, gene expression profiling will be done using next-generation sequencing techniques (Illumina, MiSeq®) on neurons derived from the drug delivery systems. Results and Discussion: Guggulsterone-loaded and purmorphamine-loaded microspheres were successfully prepared at an encapsulation efficiency of 31.6 ± 4.8% and 84.7 ± 2.3%, respectively. The average diameter of microspheres was 14.8 ± 5.9 µm for guggulsterone and 5.5 ± 2.6 µm for purmorphamine. Figure 1. Scanning electron micrographs of (A) guggulsterone microspheres and (B) purmorphamine microspheres showing a spherical and smooth morphology. Purmorphamine microspheres had a cumulative release of ~25% over 28 days. Figure 2. Cumulative release of purmorphamine over 28 days. Sample size n = 3. After 12 days, cell viability for the purmorphamine microsphere incorporated aggregates (~73%) was comparable to the negative control (~70%) suggesting low cytotoxic effects from the microspheres. These microsphere aggregates showed decreased SSEA-4 pluripotency marker expression (~27%) compared to the negative control (~45%) as expected. Conclusions: We have successfully fabricated guggulsterone and purmorphamine PCL microspheres using a single emulsion technique and shown that the purmorphamine microspheres can be incorporated in hiPSC aggregates, influencing differentiation. Such combinations of small molecules releasing microspheres with hiPSC aggregates represent a novel strategy for engineering neural tissue. The authors would like to acknowledge the Advanced Microscopy Facility at the University of Victoria.

Design and evaluation of gamma-sterilized vancomycin hydrochloride-loaded poly(ɛ-caprolactone) microspheres for the treatment of biofilm-based medical device-related osteomyelitis

Context: There is a great necessity to find and use accomplished terminal sterilization technique for industrial manufacturing, research and development studies. Gamma (γ)-sterilization has been commonly employed for wide range of products as indicated by the pharmacopoeias. However, carefully examination should be performed prior to administration since γ-radiation can cause changes in drug and polymer excipients. No information is available in literature about γ-sterilization effects on vancomycin HCl-loaded poly (ɛ-caprolactone) (PCL) microspheres.Objective: Formulations were developed using a different preparation approach for the treatment of medical device-related osteomyelitis, and γ-sterilization effects on the physicochemical characterization of the formulations were examined.Methods: Water-in-oil-in-water (w/o/w) emulsion technique using polyvinyl alcohol (PVA) in inner and outer phase was applied to prepare formulations. Physicochemical properties of the formulations were investigated before and after γ-sterilization and the antibacterial activity against Staphylococcus aureus (S. aureus) and Staphylococcus epidermidis (S. epidermidis) were measured.Results: The particle size of the nonsterilized formulations were between 58 and 134 μm. 60% or 20% of vancomycin HCl were released from 42.500 Mn or 70.000–90.000 Mn PCL microspheres, respectively, in 24 h. No difference was observed in the particle size, drug-loading efficiency, morphology, in vitro release and antimicrobial activity of the formulations after γ-sterilization (p > 0.05).

Full factorial design optimization of anti-inflammatory drug release by PCL–PEG–PCL microspheres

A biodegradable triblock poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) copolymer was successfully synthesized by ring-opening polymerization of ε-caprolactone, and was characterized by intrinsic viscosimetry, (1)H nuclear magnetic resonance, infrared spectroscopy and X-ray diffraction. Copolymer microparticles loaded with ibuprofen were prepared by an oil-in-water (o/w) emulsion solvent evaporation process. They were carefully weighted and characterized through their zeta potential. In this work, 4 selected process parameters (shaking speed X1, time of contact X2, poly(vinyl alcohol) concentration X3, and ibuprofen concentration X4) were adjusted at 2 different values. For each of the 16 experimental conditions, repeated twice, the drug encapsulation efficiency of the microspheres was determined, according to the following definition: EE (X1, X2, X3, X4)=mass of encapsulated ibuprofen/total weight of ibuprofen. A "full factorial design method" was applied to analyze the results statistically according to a polynomial fit and to determine the optimal conditions for the microencapsulation of the ibuprofen through an accurate statistical protocol. The microparticles obtained exhibit a spherical shape as shown by electron microscopy.

PCL microspheres tailored with carboxylated poly(glycidyl methacrylate)-REDV conjugates as conducive microcarriers for endothelial cell expansion.

Microcarrier cell culture systems provide one of the most promising techniques for cell amplification due to their high surface area-to-volume ratio. In this study, biodegradable polycaprolactone (PCL) microspheres tethered with carboxylated poly(glycidyl methacrylate)-REDV conjugates were developed by a combination of surface-initiated atom transfer radical polymerization (ATRP) and azide-alkyne click chemistry as conducive microcarriers for rapid cell expansion of human umbilical vein endothelial cells (HUVECs). Azido-terminated poly(glycidyl methacrylate) (PGMA-N3) brushes were grafted onto the PCL microspheres by surface-initiated ATRP. Subsequent carboxylation of PGMA-N3 brushes was accomplished by azide-alkyne click reaction with hexynoic acid. REDV peptides were covalently conjugated to the pendent carboxyl groups on the side chain of carboxylated PGMA-COOH brushes via carbodiimide chemistry to enhance the cytocompatibility of the three-dimension (3D) PCL scaffolding system. Success in each functionalization step was ascertained by the measurement of attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and wet laser particle size analysis. In vitro cell-loading assay of HUVECs demonstrated a significant improvement of cell adhesion and proliferation on the REDV-immobilized PCL microsphere surfaces, and a confluent layer of HUVECs was formed after 7 days of incubation. The highly biocompatible and transportable nature of functionalized PCL microcarriers offers significant potential as a cell expansion platform.

In vitro evaluation of effects of sustained anti-TNF release from MPEG-PCL-MPEG and PCL microspheres on human rheumatoid arthritis synoviocytes

Anti-tumor necrosis factor α (TNFα) drugs such as etanercept (ETN) have been mostly used in systemic treatment of rheumatoid arthritis. To eliminate the side effects in long-term treatments and to achieve a local sustained anti-inflammatory effect, a controlled drug delivery system is needed for anti-TNFα drugs. This study aims to develop novel injectable microcarriers of ETN that can provide long-term controlled release of this protein drug upon intra-articular application. In this study, poly(ε-caprolactone) (PCL) and its copolymer with poly(ethylene glycol), methoxypoly(ethylene glycol)-poly(ε-caprolactone)-methoxypoly(ethylene glycol) microspheres (MPEG-PCL-MPEG) were compared for their prospective success in rheumatoid arthritis treatment. Microspheres with smooth surface of a mean particle diameter of approximately 5 μm were prepared with both polymers. MPEG-PCL-MPEG microspheres had higher encapsulation efficiency than PCL microspheres. The activity of encapsulated ETN within MPEG-PCL-MPEG microspheres also retained while 90% of the activity of ETN within PCL microspheres could retain during 90-day release. MPEG-PCL-MPEG microspheres showed faster ETN release compared to PCL microspheres in various release media. Cumulative amounts of ETN released from both types of microspheres were significantly lower in cell culture medium and in synovial fluids than in phosphate buffered saline. This was mainly due to protein adsorption onto microspheres. Hydrophilic MPEG segment enhanced ETN release while preventing protein adsorption on microspheres compared to PCL. Sustained ETN release from microspheres resulted with a significant decrease in pro-inflammatory cytokines (TNFα, IFNγ, IL-6, IL-17) and MMP levels (MMP-3, MMP-13), while conserving viability of fibroblast-like synoviocytes compared to the free drug. Results suggest that MPEG-PCL-MPEG is a potential copolymer of PCL that can be used in development of biomedical materials for effective local treatment purposes in chronic inflammatory arthritis owing to enhanced hydrophilicity. Yet, PCL microspheres are also promising systems having good compatibility to synoviocytes and would be especially the choice for treatment approach requiring longer term and slower release.

Characteristics and release profiles of MPEG-PCL-MPEG microspheres containing immunoglobulin G

Polyester–polyether type block copolymers have attracted attention in the area of drug delivery systems with their capability in providing a broad range of amphiphilic characteristics. The aim of the present work was to prepare and characterize immunoglobulin G (IgG) loaded methoxy poly(ethylene glycol)-poly(ɛ-caprolactone)-methoxy poly(ethylene glycol) (MPEG-PCL-MPEG) microspheres as potential carrier for therapeutic monoclonal antibodies used in clinics. MPEG-PCL-MPEG triblock copolymer was synthesized by ring-opening polymerization of ɛ-caprolactone initiated by MPEG and then characterized. Microspheres were prepared by double emulsion-solvent evaporation method and their properties were compared with those of PCL microspheres. Microspheres had spherical shape with a mean particle size around 6μm. MPEG-PCL-MPEG microspheres had higher encapsulation efficiency than PCL microspheres. After 90 days of release, 30±2% and 57±3% of the bioactivity of IgG released from non-irradiated PCL and MPEG-PCL-MPEG microspheres were protected, respectively. Presence of MPEG in microspheres provided more controlled IgG release rate and protected IgG from denaturation during γ-irradiation (20±3% and 49±2% for PCL and MPEG-PCL-MPEG microspheres, respectively). In vitro cytotoxicity tests revealed that both MPEG-PCL-MPEG and PCL microspheres had no toxic effect on cells. This study showed that MPEG-PCL-MPEG microspheres are promising delivery systems for therapeutic monoclonal antibodies.

Engineering PLGA doped PCL microspheres with a layered architecture and an island–sea topography

Composite polymer devices have gained considerable interest in biomedical applications. In this work, a composite poly(lactic-co-glycolic acid)/poly(e-caprolactone) (PLGA/PCL) microsphere with a layered architecture and an island–sea topography was developed. PCL was found to occupy the shell layer of the microsphere, while PLGA constituted surface islands and the internal core. This subtle structure was derived from the different external and internal rates of phase separation between PCL and PLGA. The existence of the PLGA islands enhanced the hydrophilicity of the PCL shell. Mouse mesenchymal stem cells (mMSCs) were cultured and they grew well on the PLGA/PCL microspheres. The surface of the microsphere was microscopically composed of PCL sea and PLGA islands, and the mMSCs showed a trend to attach to the more hydrophilic PLGA islands and bridged between adjacent microspheres. This paper provides a new alternative to design functional microspheres for potential application in tissue repair.

Gelation of microsphere dispersions using a thermally-responsive graft polymer

Dispersions of microspheres (MSs) that form self-supporting particle gels are fundamentally interesting from the viewpoints of gel formation and mechanical properties. Here, we investigate model mixed MS/thermally responsive polymer dispersions that exist as particle gels at 37°C. The MS comprised poly(caprolactone) (PCL) and was prepared by solvent evaporation. The thermally responsive polymer contained a cationic backbone and poly(2-(2-methoxyethoxy)ethyl methacrylate) side chains and is abbreviated as PMA. Mixed PCL/PMA dispersions formed weak gels due to depletion at 20°C. At higher temperatures they formed stronger gels due to a combination of bridging of PCL MS by PMA and reinforcement by a PMA network. A key parameter controlling the mechanical properties of the reinforced MS particle gels was the volume fraction of PMA with respect to total polymer present (ΦPMA). Self-healing behaviour was observed for the gels using dynamic rheology and this depended on ΦPMA. The MS particle gel mechanical properties were conceptually described in terms of isostress and isostrain blending laws. At ΦPMA less than or greater than 0.057 the gels were dominated by the PCL or PMA networks, respectively. The latter value is suggested to be analogous to a phase inversion point.

Hydroxyapatite-coated poly(ϵ-caprolactone) microspheres fabricated via a Pickering emulsion route: effect of fabrication parameters on diameter and chemical composition

Hydroxyapatite (HAp) nanoparticle-coated poly(ϵ-caprolactone) (PCL) microspheres were fabricated via surfactant-free ‘Pickering-type’ emulsion solvent evaporation method in the absence of any molecular surfactants. HAp nanoparticles worked as an efficient stabilizer for dispersion of emulsions and microspheres. Optical microscopy, scanning electron microscopy, laser diffraction particle size analyzer, and elemental analysis were used to characterize the microspheres in terms of their size, dispersibility in aqueous media, morphology of the microspheres, and chemical compositions. The microsphere size and PCL/HAp weight ratio were successfully controlled by fabrication parameters (PCL concentration in the oil phase, HAp nanoparticle concentration in the aqueous phase, and homogenization rate): number-average diameter of the microspheres was systematically controlled over a wide range (9.2–25.1 μm) and PCL/HAp weight ratio was controlled to be between 74.0/26.0 and 99.8/0.2. Laser diffraction and optical microscopy studies of dilute aqueous dispersions indicate that the polymer microspheres disperse stably before and after evaporation of the oil. Potential applications for these HAp-coated PCL microspheres include carriers for cell delivery in tissue engineering and for sustained release of therapeutics.

Antigen adsorbed surface modified poly-ɛ-caprolactone microspheres stimulates both adaptive and innate immune response in fish

Surface modified poly-ɛ-caprolactone microspheres as an antigen carrier was explored in a fish model. Outer membrane vesicles of Edwardsiella tarda adsorbed on to surface modified poly-ɛ-caprolactone microspheres with chitosan and alginate induces both innate and adaptive immune responses which persist up to 63 days of post immunization through parenteral immunization unlike that of free and FIA adjuvented antigens. These results highlight the role of these microspheres as an adjuvant/antigen carrier in fish.

Fabrication of core–shell microspheres using alginate and chitosan–polycaprolactone for controlled release of vascular endothelial growth factor

Alginate microspheres loaded with vascular endothelial growth factor (VEGF) were prepared via an emulsification method using calcium chloride as a crosslinker. The microspheres with encapsulation efficiency of about 80% were coated by chitosan–polycaprolactone (CH–PCL) with various PCL percentages changing from around 15 to 42wt.% to fabricate core–shell alginate/CH–PCL microspheres with an average size of around 40μm. It was found that the CH–PCL coating layer on the core–shell microspheres could have a sandwich-like structure. The PCL content in the CH–PCLs and the concentration of CH–PCL solutions in preparing the microsphere functioned as two key factors to regulate the release profiles of the microspheres. Some selected alginate/CH–PCL microspheres were further crosslinked using genipin as a crosslinker, and the amount of genipin was found to be another impactful factor to mediate the release patterns of the microspheres. In vitro release measurements revealed that VEGF-release from these core–shell microspheres was controlled either by Fickian diffusion or non-Fickian transport that involves both diffusion and swelling. Some optimized core–shell microspheres were capable of maintaining sustained VEGF-release in an approximately linear manner over a period of time longer than 4weeks and did not involve a significant initial burst.

Collagen adsorption on quercetin loaded polycaprolactone microspheres: Approach for “stealth” implant

We recently experimented with collagen coating on the surface of quercetin loaded polycaprolactone microspheres by simple adsorption technique to mimic extra cellular matrix and reduce immune or inflammatory responses at the site of implants. The collagen immobilization on polymeric scaffold surfaces through various surface modification techniques was the current scenario to improve bio-integration of the polymers with the in vivo system. Nevertheless, it requires other chemicals or processing methods to modify the surface of polymers to immobilize the collagen covalently. Here protein adsorption principle is used for the coating of collagen onto the surface of solid microspheres and characterized. Optical, ATR-FTIR, SEM analysis confirm collagen coating. The reduction in burst release of the quercetin from the PCL microspheres further confirms its presence and role in the controlled release. The results indicate that the adsorption technique can be the simple strategy to coat collagen on the surface of polyester implants to develop stealth implant in shorter time with low cost technology.

Hydroxyapatite-armored poly(ε-caprolactone) microspheres and hydroxyapatite microcapsules fabricated via a Pickering emulsion route

Hydroxyapatite (HAp) nanoparticle-armored poly(ε-caprolactone) (PCL) microspheres were fabricated via a “Pickering-type” emulsion solvent evaporation method in the absence of any molecular surfactants. It was clarified that the interaction between carbonyl/carboxylic acid groups of PCL and the HAp nanoparticles at an oil–water interface played a crucial role in the preparation of the stable Pickering-type emulsions and the HAp nanoparticle-armored microspheres. The HAp nanoparticle-armored PCL microspheres were characterized in terms of size, size distribution, morphology, and chemical compositions using scanning electron microscopy, laser diffraction, energy dispersive X-ray microanalysis, and thermogravimetric analysis. The presence of HAp nanoparticles at the surface of the microspheres was confirmed by scanning electron microscopy and energy dispersive X-ray microanalysis. Pyrolysis of the PCL cores led to the formation of the corresponding HAp hollow microcapsules.