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Results for “Polylactic Acid-Polyglycolic Acid Copolymer”

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At least 19 recordsLinked to original sources
PubMed1988

A comparative scanning electron microscopic study on degradation of absorbable ligating clips in vivo and in vitro.

Using scanning electron microscopy, the degradation characteristics of two absorbable ligating clips, Absolok (polydioxanone) and Lactomer (poly-L-lactide-co-30%-glycolide) have been studied under in vivo and in vitro conditions. The rate of Absolok clip degradation was significantly greater than that of Lactomer clip degradation both in vitro and in vivo. The rate of degradation of Lactomer clips significantly increased and they showed a greater change in proportion of breakdown in vivo than in vitro compared to Absolok clips. The Absolok clip breakdown began with the formation of surface undulations which later developed into fissures. The undulations appeared on the clip surface as early as 7 days and by 2 weeks developed into fissures. The initial appearance of the fissures was at the edge of the clips particularly at the mating surface. The thickness of layers forming the fissures gradually decreased and by 15 weeks the layers appeared as very thin sheets of materials. The high energy areas (locking and molding points) were more resistant to breakdown and the remains of the clips were still present 25 weeks after initiation of the experiments. The Lactomer clips showed very little sign of degradation in vitro even after 10 weeks of incubation. However, in the in vivo experiments undulations formed on the clip surface as early as 2 weeks postimplantation. These clips also showed fissures similar to those observed on Absolok clips.

Animals↗
PubMed1988

Effect of particle size on the in vitro and in vivo degradation rates of poly(DL-lactide-co-glycolide) microcapsules.

Three different sieve size fractions of ergot-containing biodegradable microcapsules were examined both in vitro and in vivo. The sieve sizes and average particle diameter, (micron), were: less than 45-75 (mean = 30); 75-106 (mean = 79); 106-177 (mean = 130). These microcapsules contained ca. 9% drug and were produced from 50:50 poly(DL-lactide-co-glycolide). The objective was to determine the effect of particle size on in vivo and in vitro degradation rates. The microcapsules were injected into rat gastrocnemius muscle and excised and examined at various time points up to 70 days. Initially a minimal tissue response was noted which was characterized by a sharply localized acute inflammatory reaction. Following this, connective tissue and foreign body giant cells engulfed the microcapsules at 20-30 days. Only vestiges of the microcapsules were found surrounded by minimal connective tissue and foreign body giant cells after 60-70 days. The tissue reaction was a minimal, sharply localized foreign body giant cell and connective tissue process for all three size groups of microcapsules. The largest microcapsules (mean = 130 microns) exhibited a slightly greater tendency to undergo in vivo and in vitro degradation relative to the other groups. However, it can be concluded that over the microcapsule size ranges examined minimal differences in the degradation properties of the polymeric matrices and consequently those of the microcapsules were noted.

Animals↗
PubMed1995

Biodegradable sponges for hepatocyte transplantation.

Liver cell transplantation may provide a means to replace lost or deficient liver tissue, but devices capable of delivering hepatocytes to a desirable anatomic location and guiding the development of a new tissue from these cells and the host tissue are needed. We have investigated whether sponges fabricated from poly-L-lactic acid (PLA) infiltrated with polyvinyl alcohol (PVA) would meet these requirements. Highly porous sponges (porosity = 90-95%) were fabricated from PLA using a particulate leaching technique. To enable even and efficient cell seeding, the devices were infiltrated with the hydrophilic polymer polyvinyl alcohol (PVA). This reduced their contact angle with water from 79 to 23 degrees, but did not inhibit the ability of hepatocytes to adhere to the polymer. Porous sponges of PLA infiltrated with PVA readily absorbed aqueous solutions into 98% of their pore volume, and could be evenly seeded with high densities (5 x 10(7) cells/mL) of hepatocytes. Hepatocyte-seeded devices were implanted into the mesentery of laboratory rats, and 6 +/- 2 x 10(5) of the hepatocytes engrafted per sponge. Fibrovascular tissue invaded through the devices' pores, leading to a composite tissue consisting of hepatocytes, blood vessels and fibrous tissue, and the polymer sponge.

Animals↗
PubMed1995

Incorporation of polylactide-polyglycolide in a cortical defect: neoangiogenesis and blood supply in a bone chamber.

Erodible polymers are an alternative to metals for fracture fixation (for example, in the malleolus) and for maxillofacial reconstruction. In this study, the vascular response to eroding polylactide-polyglycolide copolymer threads was observed chronically in a bone chamber implant, with use of intravital microscopy. A bone chamber implant loaded with 100 microns thick polylactide-polyglycolide threads was implanted into the right tibia in 15 mature female New Zealand White rabbits. Periodic intravital microscopic observations were performed from the third to the tenth or twelfth week after implantation. Vascularization, blood flow, and trabecular growth into the chambers from the medial cortex were recorded on videotape and analyzed using digital image processing. A statistically significant delay of neo-osteogenesis in the presence of this copolymer was described in an earlier report. The present report describes the measures of neoangiogenesis and blood supply; there was a significant delay in neoangiogenesis. It is suggested that both delayed angiogenesis and osteogenesis were secondary consequences of the macrophage response to slowly eroding poly-L-lactide crystal nanoparticles and the influence of reduced nutrient exchange. The lesser effect on blood supply and vascular volume fraction was seen to be linked to the slowing down of angiogenesis, as the latter allowed vessels to mature, with a widening of their calibers. This homeostatic adjustment was interpreted as being only partially successful in restoring control levels of oxygen delivery, because resulting increases in vessel surface area did not reach control levels. Thus, in the presence of eroding polylactide-polyglycolide, the oxygen supply and extravasation of other nutrients may be below normal during healing phases when the need is critical.

Analysis of Variance↗
PubMed1992

Angiopolarity of cell carriers: directional angiogenesis in resorbable liver cell transplantation devices.

The purpose of this study was to obtain directional angiogenesis of small blood vessels and capillaries to an implant made from a resorbable polymer for hepatocyte transplantation. It was intended to mimic the native acinar structure of the liver in order to facilitate replication of the cells and organ growth. The implant device structure was designed for injection to minimize surgical trauma. Hollow microspheres with an open porous wall structure and one large central opening were made from poly(d,l-lactic-co-glycolic acid) (85:15 lactic:glycolic). This polymeric scaffold was seeded with hepatocytes and implanted into the abdominal wall muscle of syngeneic Fisher rats. Specimens explanted up to 56 days p.o. showed hepatocyte survival and the development of a directional blood supply. This phenomenon is coined "angiopolarity". The study should help in addressing the issue as to whether avascular cell implants with post-transplantation organ growth should be attempted. Processing options in applying heat to the polymer solution allow manufacturing of larger microspheres with different diameters of central openings. This would allow the use of the scaffold for other cell transplantations than hepatocytes.

Animals↗
PubMed1992

Clearance of microsphere-entrapped 5-fluorouracil and cytosine arabinoside from the vitreous of primates.

Experiments were conducted with biodegradable microspheres containing antimetabolites to assess the release of the drugs from the microspheres into the vitreous cavity of primates. Microspheres containing a mixture of radiolabeled and cold cytosine arabinoside (Ara-C) or 5-fluorouracil (5-FU) were prepared using a solvent evaporation process. The copolymers of poly (lactic) and poly (glycolic) acid (85:15) and drug was dissolved in a mixture of chloroform and acetone. The solutions were then emulsified in an aqueous solution of polyvinyl alcohol and stirred for 24 hours to evaporate the organic solvent. A 0.1 mL aliquot of a suspension of the microspheres was then injected into one eye of eight African Green monkeys. Half received 250 +/- 10 micrograms of Ara-C and the others 375 +/- 15 micrograms of 5-FU. The concentration in the vitreous was then measured by removing a 0.1 mL sample of vitreous at 1, 2, 4 and 11 days after injection. Both drugs released from microspheres were still detectable in the eye 11 days after injection and the clearance kinetics were similar for both drugs. The results indicate that the microspheres appear promising as a slow drug-delivery system for future investigations in conjunction with these and other antimetabolites suitable for the treatment of PVR.

Animals↗
PubMed1991

Sustained release of isoniazid in vivo from a single implant of a biodegradable polymer.

In order to solve the problem of poor patient compliance, attempts were made to prolong the bioavailability of antimycobacterial drugs after a single administration. A single implant of polylactic-co-glycolic acid (PLGA) co-polymer containing isoniazid ensured its sustained release up to 6 weeks. The levels are comparable with those obtained from daily doses. Homogenates of liver and lungs from animals killed at 6 weeks after a single implant showed high antimycobacterial activity against Mycobacterium tuberculosis. Sera from the implant and daily dose group animals showed no significant difference in renal, hepatic and haematological parameters. The implant caused no local or systemic toxicity.

Biocompatible Materials↗
PubMed1992

Gel casting of resorbable polymers. 2. In-vitro degradation of bone graft substitutes.

Gel cast microporous materials produced from: slow resorbing, poly(L-lactide); fast resorbing, 50:50 poly(DL lactide coglycolide); and blends of these polymers have been characterized by weight loss, compression testing and thermal analysis after immersion in phosphate buffered saline (37 degrees C, pH 7.4) for times up to 6 months. Increasing weight loss and reduction in compressive properties with immersion time were measured. Blending reduces the rate of weight loss and material shrinkage relative to the copolymer. Thermal analysis of degraded samples revealed evidence of reorganization of the crystalline phase in poly(L-lactide) and a crystalline component in the 50:50 copolymer, estimated at 5-7% of the original material content, which is probably responsible for gel formation. Thermograms of the blend are effectively a superposition of thermograms of the individual components. Gel casting shows potential for varying the resorption rate, form stability and compressive properties of micro/macroporous bone graft substitutes.

Biocompatible Materials↗
PubMed1991

Controlled release microparticles for vaccine development.

The primary and secondary sera IgG antibody responses to ovalbumin (OVA) entrapped in biodegradable poly(lactide-co-glycolide) (PLGA) microparticles were compared with the responses obtained with soluble OVA. In addition, OVA in PLGA microparticles was also administered after dispersion in an immunostimulatory vehicle, Freund's incomplete adjuvant (FIA). The primary IgG responses to OVA in microparticles/FIA were significantly greater than the responses to soluble OVA from day 14 to day 42, when booster immunizations were administered. From day 49 to the end of the study at day 84, the responses to OVA, both in microparticles alone and in microparticles/FIA, were significantly greater than the responses to soluble OVA. Nevertheless, the responses obtained for OVA in microparticles or microparticles/FIA were, in general, not as high as those obtained with OVA in Freund's complete adjuvant.

Animals↗
PubMed1987

Restoration of bone discontinuities in dogs using a biodegradable implant.

A copolymer (polylactic acid: polyglycolic acid) was combined with a proteolipid (PL) and the resulting implant complex was rigidly fixed into discontinuities in the mandibles of 25 adult, foxhound dogs. Identically prepared control discontinuities in contralateral sites in the same animals were also rigidly fixed but did not receive the complex. At four, eight, 12, 24, and 40 weeks the dogs were killed and implant and controls were prepared for histomorphometry. Histomorphometric evaluation revealed a linear increase of bony reparative elements in the implants over 40 weeks that exceeded those of the nontreated control sites. The copolymer-PL implant, therefore, may provide an alternative to autogeneic and allogeneic bone substances.

Animals↗
PubMed1995

In vitro comparison of parameters affecting the fixation strength of sagittal split osteotomies.

PURPOSE: The goal of this study was to determine how different parameters affect the bending strength of human cadaver mandibles that have undergone a sagittal split osteotomy. MATERIALS AND METHODS: The effects of screw material (titanium [Ti] vs polylactic acid/polyglycolic acid [PLA/PGA]), screw configuration (linear vs inverted L-shape), screw diameter (2.0 mm vs 2.7 mm), material into which screws were inserted (human mandible, bovine rib, synthetic polymer), and loading rate (1.0 mm/min vs 10.0 mm/min) were quantified. Also, biomechanical principles were used to model shear stress and displacement. Variable lever arms, screw material, screw diameter, screw configuration, distance between screws, and bone properties were all evaluated in this model. RESULTS: Accounting for variable mandible geometries and differentiating between deflections (and shear stresses) due to bending and due to torsion, in vitro mechanical testing revealed that there was a statistically significant difference in total shear stress at 3 mm of deflection depending on screw material (Ti > PLA/PGA), screw diameter, and material into which screws are inserted (mandibles > ribs = synthetic polymer). There was no significant difference in total shear stress depending on screw configuration or strain rate. CONCLUSION: Total shear stress and deflections are important and more viable parameters than load to assess parameters of clinical importance in osteotomy or fracture fixation.

Aged↗
PubMed1984

The evaluation of various bioabsorbable materials on the titanium fiber metal tracheal prosthesis.

A new type of tracheal prosthesis was studied. It consists of a rigid, porous cylinder of titanium fiber metal coated with a polymer that provides an initial air seal and then is absorbed to permit subsequent fibrous tissue ingrowth and reepithelialization. Fifteen such cylinders measuring 50 mm by 26 mm were coated with one of the following polymers: polycaprolactone 700 (3 coated internally and 3 externally); a copolymer of 75% poly-L-lactic acid and 25% polyglycolic acid (3 coated internally and 3 externally); and polyglactin 910 (3 coated externally). Fifteen kennel-conditioned mongrel dogs, each randomly assigned to one of these five groups, underwent implantation of the prosthesis through a right thoracotomy into a 5-cm defect in the distal intrathoracic trachea. There were no immediate postoperative deaths, and no instances of major air leak from the prosthesis. One animal died after two weeks secondary to a lower respiratory tract infection. Bronchoscopic evaluation revealed varying degrees of tissue ingrowth into the prostheses, with no evidence of infection or distal accumulation of secretions. Histological evaluation showed superior tissue ingrowth and reepithelialization with internally coated prostheses; two out of three polymers gave good results.

Animals↗
PubMed2026

An All-in-One Photothermal Nanocomposite Hydrogel for Controlling Inducible Transgene Expression.

We have developed a remotely near-infrared (NIR)-activated, implantable fibrin hydrogel for the controlled induction of transgene expression, designed to decouple the therapeutic efficacy of rapamycin from its systemic toxicity. Rapamycin, a drug widely used in clinical practice as an immunosuppressant and antiproliferative agent, is a potent transcriptional inducer that enables tightly regulated temporal transgene expression through chemically induced dimerization. However, its utility as a dimerizer is hindered by the unintended systemic immunosuppression and off-target effects inherent to its conventional administration. To address this, we developed poly(lactic-co-glycolic acid) (PLGA) nanoparticles to encapsulate rapamycin, aiming to facilitate localized delivery and enhance drug stability. Engineered cells harboring a dual heat- and dimerizer-responsive gene switch exhibited robust reporter transgene expression following nanoparticle treatment and thermal activation. Nanoencapsulation preserved rapamycin activity against thermal and hydrolytic degradation, enabling superior, long-term dimerizer function compared to the free drug. To create a remotely actuated platform, we developed photothermal hydrogels by incorporating hollow gold nanoparticles and rapamycin-loaded PLGA nanoparticles within a fibrin matrix hosting the reporter cells. In mice, NIR irradiation of subcutaneously implanted constructs achieved transgene induction levels comparable to systemic administration of rapamycin. Notably, nanoparticle-mediated delivery resulted in negligible circulating rapamycin concentrations. Furthermore, localized rapamycin release initially promoted a pro-healing M2 macrophage phenotype, followed by a late-stage transition toward an M1-dominant profile that likely facilitated the clearance of scaffold degradation products. In hydrogels incorporating cells harboring a gene switch to control human VEGF165 production, NIR irradiation triggered a robust angiogenic cascade characterized by transient erythema followed by an increase in CD31+ microvascular density. Collectively, these data demonstrate the potential of this light-triggered and rapamycin-dependent platform as a customizable and safe tool for achieving the control required to advance the next-generation of site-specific, transgenic protein therapies.

Animals↗
PubMed2025

Immunomodulatory Nanoparticles Induce Autophagy in Macrophages and Reduce Mycobacterium tuberculosis Burden in the Lungs of Mice.

Tuberculosis (TB) is the leading cause of death from infectious disease. Macrophages are the primary immune responders and become the primary host cells for the causative agent Mycobacterium tuberculosis. Following the uptake of M. tuberculosis, the inherent antimicrobial action of macrophages is dampened, enabling the bacterium to reside within these cells and multiply. Rising resistance of M. tuberculosis to antibiotics has led to the investigation of novel approaches for the treatment of TB. Here, we report a host-directed approach, employing biomimetic Curdlan poly(lactic-co-glycolic acid) (C-PLGA) nanoparticles (NPs), and examine autophagy induction in infected macrophages, eradication of M. tuberculosis and immune modulation in a mouse model. We demonstrate that the NPs induce autophagy in M. tuberculosis-infected macrophages. Treatment of H37Rv infected C57BL/6 mice with these NPs reduced M. tuberculosis burden in the lungs of mice and modulated cytokines and chemokines and this work demonstrates that these immunomodulatory NPs are a potential treatment approach for TB.

Animals↗
PubMed1991

Controlled delivery systems for proteins based on poly(lactic/glycolic acid) microspheres.

This paper describes an investigation of the use of poly(lactic/glycolic acid) polymers for long-term delivery of high molecular weight, water-soluble proteins. Poly(lactic/glycolic acid) (PLGA) microspheres, containing (fluorescein isothiocyanate)-labeled bovine serum albumin and (fluorescein isothiocyanate)-labeled horseradish peroxidase, were prepared by a modified solvent evaporation method using a double emulsion. The microspheres were spherical with diameters of 55-95 microns and encapsulated more than 90% of the protein. The preparation method was gentle and maintained enzyme activity and protein solubility. Stability studies showed that the encapsulation of an enzyme inside PLGA microspheres can protect them from activity loss. When not placed inside PLGA microspheres, (fluorescein isothiocyanate)-labeled horseradish peroxidase lost 80% of its activity in solution at 37 degrees C in a few days, whereas inside the PLGA microspheres it retained more than 55% of its activity after 21 days of incubation at 37 degrees C. In vitro release studies revealed that different release profiles (i.e., near-constant or biphasic) and release rates can be achieved by simply modifying factors in the preparation procedure such as mixing rate and volume of inner water and organic phases. Degradation studies by scanning electron microscopy and gel-permeation chromatography suggested that the mechanism responsible for protein release is mainly through matrix erosion.

Biological Availability↗
PubMed1990

Influence of average molecular weights of poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 on phase separation and in vitro drug release from microspheres.

The phase separation of fractionated poly(DL-lactic acid-co-glycolic acid) copolymers 50/50 was determined by silicone oil addition. Polymer fractionation by preparative size exclusion chromatography afforded five different microsphere batches. Average molecular weight determined the existence, width, and displacement of the "stability window" inside the phase diagrams, and also microsphere characteristics such as core loading and amount released over 6 hr. Further, the gyration and hydrodynamic radii were measured by light scattering. It is concluded that the polymer-solvent affinity is largely modified by the variation of average molecular weights owing to different levels of solubility. The lower the average molecular weight is, the better methylene chloride serves as a solvent for the coating material. However, a paradoxical effect due to an increase in free carboxyl and hydroxyl groups is noticed for polymers of 18,130 and 31,030 SEC (size exclusion chromatography) Mw. For microencapsulation, polymers having an intermediate molecular weight (47,250) were the most appropriate in terms of core loading and release purposes.

Drug Compounding↗