Poly Lactic Acid Block Copolymer Research Articles

In Vivo Degradation Studies of PGA-PLA Block Copolymer and Their Histochemical Analysis for Spinal-Fixing Application.

Polylactic acid (PLA) and polyglycolic acid (PGA) are well-known medical-implant materials. Under the consideration of the limitations of degradable polymeric materials, such as weak mechanical strength and by-product release through the biodegradation process under in vivo environments, PLA–PGA block copolymer is one of the effective alternative implant materials in the clinical field. In our previous study, two types of extremely effective PGA–PLA copolymers (multi/tri-block PGA–PLA copolymers) were synthesized. These synthesized block copolymers could overcome aforementioned issues and also showed good biocompatibility. In this study, the PGA–PLA block copolymers with large molecular weight were synthesized under the same chemical scheme, and their bio durability was confirmed through the in vivo degradation behavior and histochemical analyses (by hematoxylin and eosin and immune staining) in comparison with commercial PLGA random copolymer (medical grade). Specimens for the degradation test were investigated by SEM and X-ray diffractometer (XRD). As a result, the synthesized PGA–PLA block copolymer showed good biocompatibility and had a controlled biodegrading rate, making it suitable for use in resorbable spinal-fixation materials.

Polylactic acid block copolymer grafted temozolomide targeted nano delivery in the treatment of glioma

Gliomas are tumors of the central nervous system; they can be invasive and are commonly treated by surgical resection, chemo, and radiotherapy. Removal of a glioma is dangerous and not always successful. Temozolomide (TMZ), the first-line chemotherapy drug for gliomas, inhibit tumor recurrence, and metastasis to some extent. TMZ is often accompanied by side effects such as anemia, fever, constipation, and more. Here using a double-targeted Kunitz domain Angiopep-2 (ANG) modified block copolymer poly(lactic acid)-polyethylene glycol (PEG-PLA) coated with TMZ, we constructed a nano-delivery system (ANG@PLA-PEG/TMZ) that crosses the blood-brain barrier (BBB) to treat gliomas.

Enhancing the specific T cell immune response against micro- and nanoparticle immobilized antigen

The current study was a part of the project on generating viral particle traps occurring due to covalent immobilization on the interface of recombinant virus-specific polymer-based nano- and microparticles. It is assumed that protein-particle conjugates could be able to bind virions followed by engulfment by immune cells. The study was aimed to examine the effect of polylactic acid (PLA) and PLA block-copolymer with polyethylene glycol (PLA-PEG)-based micro- and nanoparticles on the cellular immune response against polymeric particle-bound antigen. Materials and methods. A recombinant chimeric protein beta-2-microglobulin — green fluorescent protein (β2M-sfGFP) was obtained by affine chromatography. The recombinant protein was immobilized onto the polymer particles, which were further used for mice immunization. Female F1 hybrid mice (CBA x C57BL) in experimental and control groups consisted of 4–6-month-old 15 animals (weighted 20–25 g). Intracellular cytokine staining was used to evaluate the cellular immune response. Results and discussion. It was shown that the nanoparticles of PLA block-copolymer with polyethylene glycol (PLA-PEG) were able to bind 10 microgram protein per 1 mg polymer. The polylactic acid nanoparticles were able to bind 2,3 microgram protein per 1 mg polymer. In experiment, mice in group 1 were immunized with 100 nm PLA-PEG particle-β2M-sfGFP conjugate, in group 2 — with same particles together with soluble β2M-sfGFP. In group 3, mice were immunized with 1400 nm PLA particles-β2M-sfGFP conjugate, and in group 4 — with same particles together with soluble protein. The spleens isolated 2 weeks after the four-time intraperitoneal immunization. Comparison of immune response between groups was assessed by nonparametric Kruskal–Wallis criterion with Tukey correction. It was shown that the number of antigen-specific CD4+ T cells produced to model protein was significantly higher after immunization with particle-β2M-sfGFP conjugate, as compared to control groups, wherein immunization was performed with a mixture of protein and unmodified particles (p 0.001). It was found that the number of antigen-specific CD8+ T cells formed against β2m-sfGFP did not differ between all groups examined.

Novel potential nanostructures for photodynamic therapy

To develop potent and safer formulation of photosensitizer for cancer photodynamic therapy (PDT), we tried to formulate hydrophobic porphyrin derivative, photoprotoporphyrin IX dimethyl ester (PppIX-DME), into polymeric nanoparticles composed of polyethylene glycol and polylactic acid block copolymer (PN-Por). The mean particle size of PN-Por prepared was around 80 nm and the zeta potential was determined to be weakly negative. In vitro phototoxicity study for PN-Por clearly indicated the significant phototoxicity of PN-Por for three types of tumor cells tested (Colon-26 carcinoma (C26), B16BL6 melanoma and Lewis lung cancer cells) in the PppIX-DME concentration-dependent fashion. Furthermore, it was suggested that the release of PppIX-DME from PN-Por would gradually occur to provide the sustained release of PppIX-DME. In vivo pharmacokinetics of PN-Por after intravenous administration was evaluated in C26 tumor-bearing mice, and PN-Por exhibited low affinity to the liver and spleen and was therefore retained in the blood circulation for a long time, leading to the efficient tumor disposition of PN-Por. Furthermore, significant and highly effective anti-tumor effect was confirmed in C26 tumor-bearing mice with the local light irradiation onto C26 tumor tissues after PN-Por injection. These findings indicate the potency of PN-Por for the development of more efficient PDT-based cancer treatments.

Formulation and Evaluation of Paclitaxel-Loaded Polymeric Nanoparticles Composed of Polyethylene Glycol and Polylactic Acid Block Copolymer

To develop potent paclitaxel (PTX) formulations for cancer chemotherapy, we formulated PTX into polymeric nanoparticles composed of polyethylene glycol (PEG) and polylactic acid (PLA) block copolymer (PN-PTX). First, the physicochemical properties of PN-PTX prepared were assessed; the mean particle size was around 80 nm and the zeta potential was found to be almost neutral. Next, the in vitro PTX release property was assessed by a dialysis method. Although rapid release of PTX was observed just after dosing, around 70% of PTX was stably incorporated in polymeric nanoparticles for a long time in the presence of serum. Then, the in vivo pharmacokinetics of PN-PTX after intravenous administration was investigated in Colon-26 (C26) tumor-bearing mice. Both polymeric nanoparticles and PTX incorporated exhibited a long blood circulating property, leading to enhanced permeability and retention (EPR) effect-driven, time-dependent tumor disposition of PTX. Tumor distribution increased gradually for 24 h, and tissue uptake clearance of polymeric nanoparticles in the liver and spleen was lower than that of PEG liposomes. Since these results indicated that the in vivo disposition characteristics of PN-PTX were very favorable, we then evaluated the anti-tumor effect of PN-PTX in C26 tumor-bearing mice. However, PN-PTX did not exhibit any significant anti-tumor effect, presumably due to the poor PTX release from polymeric nanoparticles. From these results, it is considered that the favorable pharmacokinetic properties of nanoparticles and the drug incorporated do not always lead to its potent in vivo pharmacological activity, suggesting the importance of PTX release properties within tumor tissues.

Evaluation of Polyethylene Glycol/Polylactic Acid Films in the Prevention of Adhesions in the Rabbit Adhesion Formation and Reformation Sidewall Models

Objective: To assess the efficacy of bioresorbable films consisting of various polyethylene glycol 6000 and polylactic acid block copolymers on the formation and reformation of adhesions in rabbit models of adhesion development between the sidewall to the adjacent cecum and bowel. The composition of the different polymers was expressed by the number of monomeric units in the block, namely, ethylene oxide (EO) and lactic acid (LA), respectively. Design: Studies of the efficacy of EO/LA films were conducted in rabbit sidewall adhesion formation studies in the presence and absence of blood and in rabbit adhesion reformation studies. REPEL (Life Medical Sciences, Edison, NJ), a film of EO/LA ratio 3.0 manufactured under commercial conditions, was also tested in these animal models. Setting: University-based laboratory. Animals: New Zealand white rabbits. Intervention(s): Placement of films of various EO/LA ratios at the site of injury to the parietal peritoneum. Main Outcome Measure(s): Adhesion formation and reformation. Result(s): Films of various EO/LA ratios, Seprafilm (Genzyme, Cambridge, MA) and Interceed (Johnson and Johnson Medical, Arlington, TX) placed over an area of excised sidewall at the time of initial injury were highly efficacious in the prevention of adhesion formation. A film of EO/LA ratio 3.7, in contrast with Interceed, was also shown to maintain maximal efficacy in the reduction of adhesion formation in the presence of blood. Further, a film of EO/LA ratio 3.0 produced under commercial conditions, REPEL, was highly efficacious in reducing adhesion development in the rabbit models of adhesion and reformation. Conclusion(s): These studies suggest that bioresorbable EO/LA films reduced adhesion development in rabbit models of adhesion formation and reformation.