Poly DL-lactide Research Articles

Increased Runx2 expression associated with enhanced Wnt signaling in PDLLA internal fixation for fracture treatment.

Poly-D-L lactide (PDLLA) biodegradable implants to heal fractures are widely applied in orthopedic surgeries. However, whether the process of fracture healing is regulated differently when PDLLA is used compared with traditional metal materials remains unclear. Runt-related transcription factor 2 (Runx2) and canonical Wnt signaling are essential and may interact reciprocally in the regulation of osteogenesis during bone repair. In the present study, a rat femoral open osteotomy model was used to compare the curative efficacy of a PDLLA rod and Kirschner wire under intramedullary fixation for fracture treatment. The dynamic expression of Runx2 and key components of the canonical Wnt signaling in callus tissue during fracture healing was also investigated. The results of the current study indicate that at weeks 4 and 6 following fixation, the callus bone structural parameters of microCT were significantly improved by PDLLA rod compared to that of Kirschner wire. In addition, at weeks 4 and 6 after fixation, the protein and mRNA expression of Runx2 and the positive regulators of canonical Wnt signaling, such as Wnts and β-catenin, were significantly increased. However, the protein and mRNA expression levels of the negative regulators of canonical Wnt signaling, such as glycogen synthase kinase-3β, were significantly decreased in callus tissue when treated with PDLLA rod compared with Kirschner wire. Collectively, these data indicate that compared to the traditional metal material, using PDLLA internal fixation for fracture treatment may further improve bone formation, which is associated with the increased expression of Runx2 and the enhancement of canonical Wnt signaling.

Patterned Fibers Embedded Microfluidic Chips Based on PLA and PDMS for Ag Nanoparticle Safety Testing.

A new method to integrate poly-dl-lactide (PLA) patterned electrospun fibers with a polydimethylsiloxane (PDMS) microfluidic chip was successfully developed via lithography. Hepatocyte behavior under static and dynamic conditions was investigated. Immunohistochemical analyses indicated good hepatocyte survival under the dynamic culture system with effective hepatocyte spheroid formation in the patterned microfluidic chip vs. static culture conditions and tissue culture plate (TCP). In particular, hepatocytes seeded in this microfluidic chip under a flow rate of 10 μL/min could re-establish hepatocyte polarity to support biliary excretion and were able to maintain high levels of albumin and urea secretion over 15 days. Furthermore, the optimized system could produce sensitive and consistent responses to nano-Ag-induced hepatotoxicity during culture. Thus, this microfluidic chip device provides a new means of fabricating complex liver tissue-engineered scaffolds, and may be of considerable utility in the toxicity screening of nanoparticles.

Shape memory effect of thermal-responsive nano-hydroxyapatite reinforced poly-d-l-lactide composites with porous structure

In this study, the effect of the inclusion of nano-hydroxyapatite (nano-HAp) and the porous structure on the shape memory behavior of poly-d-l-lactide (PDLLA) composites was investigated. Porous, thermal-responsive shape memory composites, PDLLA/nano-HAp, were prepared by a newly developed polymer coagulation, particulate leaching, and cold compression moulding technique. The inclusion of nano-HAp to PDLLA led to a higher shape memory transition temperature, improved mechanical strength and larger recovery force as compared with the neat PDLLA. The nanocomposite with 10 wt% of nano-HAp exhibited the best shape fixity and recoverability with the shortest recovery time. Further increase in the filler content of nano-HAp would reduce the recovery force and prolong the recovery time due to restriction in the movement of the amorphous PDLLA chain segments. The morphologies, thermal properties and shape memory behavior were measured by scanning electron microscopy, thermal gravimetric analyzer, differential scanning calorimeter, dynamic mechanical analysis, physical bending test and cyclic thermo-mechanical test. These results provide important information for designing biomedical devices using this novel type of bioabsorbable shape memory polymer composite.

Actuation Behavior of Polylactic Acid Fiber Films Prepared by Electrospinning.

A poly-DL-lactide (PLA) fiber film was prepared using the electrospinning method. This film consisted of randomly oriented PLA nanofibers. Consequently, it had sponge-like structure and was quite soft compared to PLA films prepared by spin coating. The average diameter of the fibers and the density of the film were 730 nm and 20%, respectively. By applying a voltage, the PLA film was subjected to electric-field-induced strain: expansion and compression in the thickness direction. When a voltage of -200 V was applied to the film, its thickness shrank from 13.5 µm to 10.0 µm (a 26% reduction). Electric-field-induced strain can occur via two different mechanisms: The first is electrostrictive behavior. That. is, in a highly electric field region, a change of film thickness occurs (compression only) from the electrostatic force between electrodes. The second mechanism is piezoelectric-like behavior that occurs in racemic PLA, wherein a PLA nanofiber is expanded and compressed by applying positive and negative voltage. Such piezoelectric-like behavior was not observed in spin-coated PLA films.

HPMA-based block copolymers promote differential drug delivery kinetics for hydrophobic and amphiphilic molecules

We describe a method how polymeric nanoparticles stabilized with (2-hydroxypropyl)methacrylamide (HPMA)-based block copolymers are used as drug delivery systems for a fast release of hydrophobic and a controlled release of an amphiphilic molecule. The versatile method of the miniemulsion solvent-evaporation technique was used to prepare polystyrene (PS) as well as poly-d/l-lactide (PDLLA) nanoparticles. Covalently bound or physically adsorbed fluorescent dyes labeled the particles’ core and their block copolymer corona. Confocal laser scanning microscopy (CLSM) in combination with flow cytometry measurements were applied to demonstrate the burst release of a fluorescent hydrophobic drug model without the necessity of nanoparticle uptake. In addition, CLSM studies and quantitative calculations using the image processing program Volocity® show the intracellular detachment of the amphiphilic block copolymer from the particles’ core after uptake. Our findings offer the possibility to combine the advantages of a fast release for hydrophobic and a controlled release for an amphiphilic molecule therefore pointing to the possibility to a ‘multi-step and multi-site’ targeting by one nanocarrier. Statement of SignificanceWe describe thoroughly how different components of a nanocarrier end up in cells. This enables different cargos of a nanocarrier having a consecutive release and delivery of distinct components. Most interestingly we demonstrate individual kinetics of distinct components of such a system: first the release of a fluorescent hydrophobic drug model at contact with the cell membrane without the necessity of nanoparticle uptake. Secondly, the intracellular detachment of the amphiphilic block copolymer from the particles’ core after uptake occurs. This offers the possibility to combine the advantages of a fast release for a hydrophobic substance at the time of interaction of the nanoparticle with the cell surface and a controlled release for an amphiphilic molecule later on therefore pointing to the possibility to a ‘multi-step and multisite’ targeting by one nanocarrier. We therefore feel that this could be used for many cellular systems where the combined and orchestrated delivery of components is prerequisite in order to obtain the highest efficiency.

A novel bioactive nerve conduit for the repair of peripheral nerve injury

The use of a nerve conduit provides an opportunity to regulate cytokines, growth factors and neurotrophins in peripheral nerve regeneration and avoid autograft defects. We constructed a poly-D-L-lactide (PDLLA)-based nerve conduit that was modified using poly{(lactic acid)-co-[(glycolic acid)-alt-(L-lysine)]} and β-tricalcium phosphate. The effectiveness of this bioactive PDLLA-based nerve conduit was compared to that of PDLLA-only conduit in the nerve regeneration following a 10-mm sciatic nerve injury in rats. We observed the nerve morphology in the early period of regeneration, 35 days post injury, using hematoxylin-eosin and methylene blue staining. Compared with the PDLLA conduit, the nerve fibers in the PDLLA-based bioactive nerve conduit were thicker and more regular in size. Muscle fibers in the soleus muscle had greater diameters in the PDLLA bioactive group than in the PDLLA only group. The PDLLA-based bioactive nerve conduit is a promising strategy for repair after sciatic nerve injury.

Curcumin loaded Poly DL lactide and hyperbranched polyglycerol blended nanofibrous scaffold for wound dressing applications

Event Abstract Back to Event Curcumin loaded Poly DL lactide and hyperbranched polyglycerol blended nanofibrous scaffold for wound dressing applications Govindaraj Perumal1, A Maya Nandkumar2 and Mukesh Doble1 1 Indian Institute of Technology Madras, Biotechnology, India 2 Sree Chitra Tirunal Institute for Medical Sciences and Technology, Division of Microbiology - Biomedical Technology Wing, India Introduction: Electrospinning is the most effective approach for fabrication of the nanofibers with suitable diameter and alignment.[1] Recently hyperbranched polyglycerols (HPGs) has emerged as a promising polymer used to make tissue engineering scaffolds due to its three dimensional architecture, presence of highly functional groups for the attachment of specific molecules to improve the cell adhesion, absorption and proliferation of the cells.[2][3] Poly DL lactic acid (PDLA) is a biodegradable, biocompatible and US FDA approved polymer for human use and widely utilized in biomedical applications such as drug delivery and tissue engineering.[4][5] Consequently, electrospinning of PDLA used to fabricate the tissue engineering scaffolds by combining with other polymers or appropriate molecules/agents. Curcumin is a poly phenolic naturally occurring compound with variety of biological functions such as anti oxidant, anti tumor, anti bacterial, anti coagulation, anti proliferation and anti inflammatory.[6][7] In this work aimed to fabricate curcumin loaded PDLA – HPG to improve the bioavailability, controlled release, stability, supporting cell attachment and proliferation to augment the healing of wound tissues. Materials and Methods: Poly DL lactide (PDLA) and hyperbranched polyglycerol (HPG) with molecular weight (Mn) of 15 kDa each were synthesized as per a reported procedure with modifications. Curcumin was purchased from Sigma Aldrich, India. Nanofibrous scaffold loaded with curcumin PDLA-HPG and PDLA-HPG were produced by electrospinning process through following parameters. PDLA (15 wt %), HPG (20 wt %) and curcumin (10 %) employed with 15 kV, 0.5 ml/hr flow rate, 12.5 cm distance at ambient conditions. The collector plate was covered with aluminium foil at predetermined distance from the blunt needle tip to collect the electrosprayed/electrospun nanofibers. A thick mat of nanofibers were carefully detached and dried under vacuum for 48 hrs at room temperature. Scanning Electron Microscopy (SEM) was used to observe the fibers properties such as orientation, diameter and surface topography. Likewise, surface wettability of the fibers were determined by water contact angle method by placing a drop of ultra pure water on the fiber mat by with Goniometer (KRUSS) Germany. In vitro curcumin release, In vitro cytocompatibility, In vitro cytoprotective, In vitro anti oxidant activity and In vitro anti inflammatory studies were performed to assess the viability and wound healing properties of the nanofibrous scaffold. Results and Discussion: SEM images of the PDLA+HPG mat revealed uniformly aligned, bead free fibers having diameter range from 200-250 nm with well inter connections (Figure 1). Significantly, curcumin loaded fibers with diameter ranging from 200-500 nm were observed (Figure 2). PDLA and PDLA-HPG blend fibers exhibited water contact angle of 90 and 55 respectively. Polymers blend displaying hydrophilic character owing to incorporation of more hydroxyl group containing HPG polymer (Figure 3). In vitro cytocompatibility of the nano fibers analyzed by MTT assay using 3T3 swiss fibroblast cells which indicating very good viability of the cells after 72 hours. Conclusion: In this work we fabricated the nanofibers scaffold of PDLA-HPG and curcumin loaded PDLA-HPG. SEM images shown uniformly aligned, well inter connected and bead free electrospun fibers obtained with higher curcumin loading capacity. Curcumin loaded nanofibers scaffold with cytoprotective and anti inflammatory qualities can have potential in wound dressing applications. IIT Madras - Facilities and funding

Osteoneogenesis due to periosteal elevation with degradable and nondegradable devices in Göttingen Minipigs.

Periosteal distraction or elevation has been known as an experimental method to induce new bone formation. Although it uses the principles of distraction osteogenesis no further osteotomy is necessary. The purpose of this study was to test devices of different materials and to evaluate the point of origin of the new bone formation. On each calvaria of twelve male adult Göttingen Minipigs three devices were implanted. The materials used were degradable PDLLA (poly-DL-lactide), PGA (polyglycolic acid) and nondegradable Ti (titanium). After a consolidation time of 2, 4 and 6 weeks days a total of 36 specimens were harvested. To identify the total amount of newly created bone, micro-CT and histological analysis were performed. All degradable devices collapsed to a certain extent within the observation time but osteoneogenesis took place in all materials after a consolidation time of 2, 4 and 6 weeks after implantation above and under the devices. No statistical significant differences between the materials were found. However, most bone formation took place in the space under the periosteum and above the devices (p < 0.001). Periosteal elevation can produce new bone formation with degradable devices, which derives from the periosteum and the underlying bone. In this interaction the periosteum seems to contain the larger share.

Reconstruction of segmental stability of goat cervical spine with poly (D, L) Lactide cage

Objective To design a type of poly (D, L) Lactide (PDLLA) cage, compare the characteristics of inter body fusion using PDLLA cage with those of titanium cage and autologous tricortical iliac crest graft in a goat cervical spine model in vivo. Methods Twenty-four goats underwent C3-4 discectomy and fusion were assigned to 3 groups, PDLLA cage group (n=8), titanium alloy cage group (n=8) and autologous iliac bone group (n=8). Radiography was performed pre- and post-operatively and 1, 2, 4, 8, and 12 weeks after operation. At the same time points, disc space height (DSH), intervertebral angle (IVA), and lordosis angle (LA) were measured. After 12 weeks, the goats were killed and fusion sites were harvested. Biomechanical testing was performed in flexion, extension, axial rotation, and lateral bending to determine the stiffness and range of motion. All cervical fusion specimens underwent histomorphological observation. Results The IVA of PDLLA cage 4 weeks after operation and DSH 8 and 12 weeks after operation was statistically greater than that of autologous iliac bone graft (P 0.05). Radiographic and histomorphological observation showed better fusion results in cage groups than in autologous bone group. Conclusion This type of PDLLA cage has excellent biocompatibility and can provide an appropriate biological environment for bone ingrowth and osteogenesis at bone-implant interface. Furthermore, PDLLA cage can maintain DSH and increase the stability of fusion segments to create a good biomechanical environment for the last bone fusion. Key words: Cervical vertebrae; Spinal fusion; Animal experimentation; Biomechanics

A Comparison of the Process of Remodeling of Hydroxyapatite/Poly-D/L-Lactide and Beta-Tricalcium Phosphate in a Loading Site.

Currently, the most commonly used bioresorbable scaffold is made of beta-tricalcium phosphate (β-TCP); it is hoped that scaffolds made of a mixture of hydroxyapatite (HA) and poly-D/L-lactide (PDLLA) will be able to act as novel bioresorbable scaffolds. The aim of this study was to evaluate the utility of a HA/PDLLA scaffold compared to β-TCP, at a loading site. Dogs underwent surgery to replace a section of tibial bone with a bioresorbable scaffold. After the follow-up period, the scaffold was subjected to histological analysis. The HA/PDLLA scaffold showed similar bone formation and superior cell and tissue infiltration compared to the β-TCP scaffold, as seen after Villanueva Goldner staining. Moreover, silver staining and immunohistochemistry for Von Willebrand factor and cathepsin K demonstrated better cell infiltration in the HA/PDLLA scaffold. The fibrous tissue and cells that had infiltrated into the HA/PDLLA scaffold tested positive for collagen type I and RUNX2, respectively, indicating that the tissue and cells that had infiltrated into the HA/PDLLA scaffold had the potential to differentiate into bone. The HA/PDLLA scaffold is therefore likely to find clinical application as a new bioresorbable scaffold.

Dynamic Assessment of the Endothelialization of Tissue-Engineered Blood Vessels Using an Optical Coherence Tomography Catheter-Based Fluorescence Imaging System.

Lumen endothelialization of bioengineered vascular scaffolds is essential to maintain small-diameter graft patency and prevent thrombosis postimplantation. Unfortunately, nondestructive imaging methods to visualize this dynamic process are lacking, thus slowing development and clinical translation of these potential tissue-engineering approaches. To meet this need, a fluorescence imaging system utilizing a commercial optical coherence tomography (OCT) catheter was designed to visualize graft endothelialization. C7 DragonFly™ intravascular OCT catheter was used as a channel for delivery and collection of excitation and emission spectra. Poly-dl-lactide (PDLLA) electrospun scaffolds were seeded with endothelial cells (ECs). Seeded cells were exposed to Calcein AM before imaging, causing the living cells to emit green fluorescence in response to blue laser. By positioning the catheter tip precisely over a specimen using high-fidelity electromechanical components, small regions of the specimen were excited selectively. The resulting fluorescence intensities were mapped on a two-dimensional digital grid to generate spatial distribution of fluorophores at single-cell-level resolution. Fluorescence imaging of endothelialization on glass and PDLLA scaffolds was performed using the OCT catheter-based imaging system as well as with a commercial fluorescence microscope. Cell coverage area was calculated for both image sets for quantitative comparison of imaging techniques. Tubular PDLLA scaffolds were maintained in a bioreactor on seeding with ECs, and endothelialization was monitored over 5 days using the OCT catheter-based imaging system. No significant difference was observed in images obtained using our imaging system to those acquired with the fluorescence microscope. Cell area coverage calculated using the images yielded similar values. Nondestructive imaging of endothelialization on tubular scaffolds showed cell proliferation with cell coverage area increasing from 15 ± 4% to 89 ± 6% over 5 days. In this study, we showed the capability of an OCT catheter-based imaging system to obtain single-cell resolution and to quantify endothelialization in tubular electrospun scaffolds. We also compared the resulting images with traditional microscopy, showing high fidelity in image capability. This imaging system, used in conjunction with OCT, could potentially be a powerful tool for in vitro optimization of scaffold cellularization, ensuring long-term graft patency postimplantation.

Degradation of poly-d-l-lactide (PDLLA) interference screws (Megafix®)

Interference screw fixation is a standard procedure in anterior cruciate ligament (ACL) replacement. Aim of this study was to evaluate the degradation process of Poly-D-L-lactide (PDLLA) interference screws used for tibial ACL graft fixation. We evaluated magnetic resonance imaging (MRI) scans of 18 patients who underwent ACL revision surgery at different time points after anatomic ACL reconstruction. At primary surgery, a tibial hybrid fixation was performed with a degradable interference (IF) screw made of PDLLA (Megafix(®)) and a button. MRI revealed three different phases of degradation of the PDLLA screw. 6-8 months after surgery the IF screw was clearly visible as a well-defined structure on MRI and CT scan. After 12-16 months, the screws appeared less defined with central ingrowths' of connective tissue. In some cases only fragmented screw material was visible. At these time points, there was a slight edema surrounding the tunnel visible on MRI. After 22 months and later, the mean screw site densities were comparable with the surrounding bone density. There was no edema or signs of inflammation around the bone tunnels visible. Presence of cystic or osteolytic changes was not detected. After 22 months, a PDLLA screw may not interfere with ACL revision surgery. Regarding the degradation process of PDLLA screws, we noted three different phases. Furthermore, the degradation process observed by MRI resembles to that described by animal studies. The PDLLA screws fully absorb and are partially replaced by bone. The degradation process in humans seems to be longer than that described in animals.

Preparation, characterization, and in vitro cytotoxicity evaluation of a novel anti-tuberculosis reconstruction implant.

BackgroundReconstruction materials currently used in clinical for osteoarticular tuberculosis (TB) are unsatisfactory due to a variety of reasons. Rifampicin (RFP) is a well-known and highly effective first-line anti-tuberculosis (anti-TB) drug. Poly-DL-lactide (PDLLA) and nano-hydroxyapatite (nHA) are two promising materials that have been used both for orthopedic reconstruction and as carriers for drug release. In this study we report the development of a novel anti-TB implant for osteoarticular TB reconstruction using a combination of RFP, PDLLA and nHA.MethodsRFP, PDLLA and nHA were used as starting materials to produce a novel anti-TB activity implant by the solvent evaporation method. After manufacture, the implant was characterized and its biodegradation and drug release profile were tested. The in vitro cytotoxicity of the implant was also evaluated in pre-osteoblast MC3T3-E1 cells using multiple methodologies.ResultsA RFP/PDLLA/nHA composite was successfully synthesized using the solvent evaporation method. The composite has a loose and porous structure with evenly distributed pores. The production process was steady and no chemical reaction occurred as proved by Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Diffraction (XRD). Meanwhile, the composite blocks degraded and released drug for at least 12 weeks. Evaluation of in vitro cytotoxicity in MC3T3-E1 cells verified that the synthesized composite blocks did not affect cell growth and proliferation.ConclusionIt is feasible to manufacture a novel bioactive anti-TB RFP/PDLLA/nHA composite by the solvent evaporation method. The composite blocks showed appropriate properties such as degradation, drug release and biosafety to MC3T3-E1 cells. In conclusion, the novel composite blocks may have great potential for clinical applications in repairing bone defects caused by osteoarticular TB.

Combinatorial Matrix Assisted Pulsed Laser Evaporation of a biodegradable polymer and fibronectin for protein immobilization and controlled release

• Combinatorial Matrix Assisted Pulsed Laser Evaporation applied to the immobilization of biodegradable polymer and protein. • Fibronectin incorporation in PDLLA matrix for controlled release. • Single step procedure for new release systems of active substances. Defined protein quantities were embedded in situ in a biodegradable polymer coating during simultaneous laser vaporization of two targets. Fibronectin (FN) and poly- dl -lactide (PDLLA) were transferred and immobilized concomitantly by Combinatorial Matrix Assisted Pulsed Laser Evaporation onto solid substrates. The film surface with gradient of composition was characterized by optical, scanning electron microscopy and profilometry. Micrometric FN packages were visualized in the polymeric matrix by confocal microscopy. The composition of FN was investigated by FTIR and μFTIR analyses in a polymeric matrix with different thickness.

Development of nanoparticulate formulations for ocular delivery of prednisolone acetate: preparation and characterization

This study describes the development and characterization of biodegradable prednisolone acetate nanoparticles indicated for ocular use. Nanoparticles were prepared by oil-in-water emulsion/solvent evaporation and nanoprecipitation techniques using poly lactide-co-glycolide (50:50) and poly DL-lactide. A 2 4 factorial design was applied to optimize the drug formulation. The effect of independent variables such as polymer type, drug-to-polymer ratio, surfactant concentration and method of preparation on entrapment efficiency (EE%), particle size, zeta potential and drug release were investigated. Further studies such as differential scanning calorimetry (DSC), X-ray diffraction (XRD) and transmission electron microscope were carried out on the selected formula. O/W emulsion/solvent evaporation technique was superior to the nanoprecipitation method in terms of EE% . In vitro release study showed extended drug release. DSC and XRD indicated the dispersion of the drug within the nanoparticles. These results demonstrate the feasibility of encapsulating prednisolone acetate inside biodegradable nanoparticles for ocular delivery.

Cell behaviors on magnetic electrospun poly-d, l-lactide nanofibers

It is widely accepted that magnetic fields have an influence on cell behaviors, but the effects are still not very clear since the magnetic field's type, intensity and exposure time are different. In this study, a static magnetic field (SMF) in moderate intensity (10mT) was employed to investigate its effect on osteoblast and 3T3 fibroblast cell behaviors cultured respectively with magnetic polymer nanofiber mats. The magnetic mats composed of random oriented or aligned polymer nanofibers were fabricated by electrospinning the mixed solution of poly-d, l-lactide (PLA) and iron oxide nanoparticles. The fiber morphology was characterized by scanning electron microscopy (SEM), the nanoparticle distribution in fiber matrix was measured with transmission electron microscope (TEM). Mechanical properties of nanofiber mats are studied by uniaxial tensile test. The results showed the nanofibers loaded with magnetic nanoparticles displayed excellent magnetic responsibility and biodegradability. In vitro cytotoxicity analysis demonstrated that the osteoblast proliferation of all fiber mats stimulated with or without SMF was increased with the increase of the culturing days. Furthermore, in the horizontal SMFs, cell orientation tended to deviate from nanofiber orientation to field direction while the nanofiber orientation is perpendicular to the field direction, while the horizonal direction of SMFs could also direct the cell growth orientation. The magnetic nanofiber mats provide a potential platform to explore the cell behaviors under the stimulation of external magnetic field.

Mechanical properties and in vitro evaluation of bioactivity and degradation of dexamethasone-releasing poly-d-l-lactide/nano-hydroxyapatite composite scaffolds

The purpose of this study was to fabricate drug-release nano-composite scaffolds and perform in vitro evaluation of their mechanical properties, bioactivity, biodegradability and drug release behaviors. Porous drug-release poly-d-l-lactide (PDLLA) composite scaffolds filled with different amounts of nano-hydroxyapatite (nano-HAp) were prepared by a technique combining polymer coagulation, cold compression moulding, salt leaching and drug coating. Apatite detected on the scaffolds after exposure to a simulated body fluid showed improvement in bioactivity and the apatite formation ability through the addition of the nano-HAp content in the composites. Nano-HAp incorporation and apatite formation made a positive impact on the mechanical properties of the scaffolds; however, plasticization and degradation of PDLLA had a negative impact. The pH-compensation effect of the composite scaffolds can reduce the risk of chronic inflammation complications. The fabrication method in this study can produce scaffolds with controllable structure, appropriate mechanical properties and degradation rates for cancellous bone repair applications.

ABAC Tetrablock Terpolymers for Tough Nanoporous Filtration Membranes

Nanoporous poly(styrene)-b-poly(isoprene)-b-poly(styrene) (PS–PI–PS) was prepared from PS–PI–PS–PLA (PLA = poly(d,l-lactide)) tetrablock terpolymer precursors. Hydroxy end-functionalized PS–PI–PS was synthesized by sequential anionic polymerizations and used to initiate the ring-opening polymerization of d,l-lactide. A combination of small-angle X-ray scattering, transmission electron microscopy and scanning electron microscopy data supports a core–shell cylinder morphology with PLA as the core component. The inherently robust mechanical properties associated with PS–PI–PS block copolymers provide the materials with enhanced flexibility and toughness compared to analogous nanoporous polystyrene samples prepared by etching of PS–PLA diblocks. Composite membranes containing nanoporous PS–PI–PS on top of microporous poly(ether sulfone) (PES) were prepared by direct spin-coating and also by a salt-plate coating/film-transfer strategy. Nanopores (dpore ≈ 15 nm) were created by a combination of reactive ion etc...

Polymeric nanocapsules with SEDDS oil-core for the controlled and enhanced oral absorption of cyclosporine

Self-microemulsifying drug delivery system (SEDDS) cored-polymeric nanocapsules (NC) were fabricated using emulsion diffusion method for the controlled oral absorption of the poorly water soluble drug, cyclosporine. Poly-dl-lactide (PDLLA) was used as the shell-forming polymer. The NCs in different polymer/oil ratios (from 25/125 to 125/125) were prepared following a solvent-diffusion method. Especially, the SEDDS oil-core compositions, which can form microemulsions on dispersion, were selected based on a pseudo-phase diagram study and further optimized based on the solubility and permeability studies. The prepared NCs were with a mean diameter of 150-220 nm and 9.4-4.5% w/w drug loading. In vivo study in rats showed that the optimized NC(50/125) and NC(100/125) released the drug in controlled way as well as enhanced the bioavailability significantly with AUC(0-24h) values of 14880.3±1470.6 and 12657.8±754.5 ng h/ml, respectively, compared to that of SEDDS-core solution (9878.9±409.6 ng h/ml). Moreover it was observed that the NCs maintained blood concentration of cyclosporine (>500 ng/ml) for 14-20 h but in the case of control formulation it was only 7.33 h. Our results suggest that the prepared NCs could be a potential carrier for the oral controlled release formulation of cyclosporine.

Effects of block copolymer properties on nanocarrier protection from in vivo clearance

Drug nanocarrier clearance by the immune system must be minimized to achieve targeted delivery to pathological tissues. There is considerable interest in finding in vitro tests that can predict in vivo clearance outcomes. In this work, we produce nanocarriers with dense PEG layers resulting from block copolymer-directed assembly during rapid precipitation. Nanocarriers are formed using block copolymers with hydrophobic blocks of polystyrene (PS), poly-ε-caprolactone (PCL), poly-d,l-lactide (PLA), or poly-lactide-co-glycolide (PLGA), and hydrophilic blocks of polyethylene glycol (PEG) with molecular weights from 1kg/mol to 9kg/mol. Nanocarriers with paclitaxel prodrugs are evaluated in vivo in Foxn1nu mice to determine relative rates of clearance. The amount of nanocarrier in circulation after 4h varies from 10% to 85% of initial dose, depending on the block copolymer. In vitro complement activation assays are conducted to correlate in vivo circulation to the protection of the nanocarrier surface from complement binding and activation. Guidelines for optimizing block copolymer structure to maximize circulation of nanocarriers formed by rapid precipitation and directed assembly are proposed, relating to the relative sizes of the hydrophilic and hydrophobic blocks, the hydrophobicity of the anchoring block, the absolute size of the PEG block, and polymer crystallinity. The in vitro results distinguish between the poorly circulating PEG5k–PCL9k and the better circulating nanocarriers, but could not rank the better circulating nanocarriers in order of circulation time. Analysis of PEG surface packing on monodisperse 200 nm latex spheres indicates that the size of the hydrophobic PCL, PS, and PLA blocks are correlated with the PEG blob size. Suggestions for next steps for in vitro measurements are made.