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PubMed2004

Preparation and characterization of cationic PLGA nanospheres as DNA carriers.

Nanoparticles formulated from biodegradable polymers such as poly(lactic acid) (PLA) and poly(lactide-co-glycolide) (PLGA) are being extensively investigated as non-viral gene delivery systems due to their controlled release characteristics and biocompatibility. PLGA nanoparticles for DNA delivery are mainly formulated by an emulsion-solvent evaporation technique using PVA as a stabilizer generating negatively charged particles and heterogeneous size distribution. The objective of the present study was to formulate cationically modified PLGA nanoparticles with defined size and shape that can efficiently bind DNA. An Emulsion-diffusion-evaporation technique to make cationic nanospheres composed of biodegradable and biocompatible co-polyester PLGA has been developed. PVA-chitosan blend was used to stabilize the PLGA nanospheres. The nanospheres were characterized by atomic force microscopy (AFM), photon-correlation spectroscopy (PCS), and Fourier transform infrared spectroscopy (FTIR). Zeta potential and gel electrophoresis studies were also performed to understand the surface properties of nanospheres and their ability to condense negatively charged DNA. The designed nanospheres have a zeta potential of 10mV at pH 7.4 and size under 200nm. From the gel electrophoresis studies we found that the charge on the nanospheres is sufficient to efficiently bind the negatively charged DNA electrostatically. These cationic PLGA nanospheres could serve as potential alternatives of the existing negatively charged nanoparticles.

Biocompatible Materials↗
PubMed2006

Microspheres from new biodegradable poly(ester amide)s with different ratios of L- and D-alanine for controlled drug delivery.

A series of biodegradable poly (ester amide)s composed of sebacic acid, dodecanediol and different ratios of the stereoisomers of L- and D-alanine were synthesized for applications in drug delivery systems. Microspheres loaded with diclofenac sodium salt, triclosan and clofazimine were prepared with the solvent evaporation technique. No influence of polymer constitution in the drug release rate was found in vitro and no degradation occurred during the period of drug release. It was shown that a sustained delivery of the hydrophilic diclofenac sodium salt in Sörensen media occurred and it was controlled by diffusion. However, exhaustion of microspheres was feasible only from the most porous matrices where channelling had an important contribution.

Alanine↗
PubMedDate not supplied

Dielectric and thermodynamic properties of biodegradable poly(D,L-lactide-co-glycolide) and the effect on the micro-encapsulation and release of captopril.

The mechanical and dielectric properties of three kinds of poly(lactic acid-coglycolic acid) (PLG) with different molecular weights and polydispersities fractioned by ultrafiltration were investigated by dynamic mechanical thermal analysis (DMTA) and dielectric measurement. All samples showed typical behaviour of amorphous polymer under different fields. Two relaxation processes were found, a secondary relaxation in glassy state at low temperature and a glass transition relaxation. The molecular weights and polydispersities of PLGs influenced significantly both relaxation, especially the relaxation strength and location. The strength of secondary relaxation was reduced and the glass transition shifted to a higher temperature when the molecular weight of PLG increased and the polydispersity decreased. The shift of glass transition temperature (Tg) might decrease the motion of the macromolecules and resulted in a higher moduli of rubbery PLG at the temperature of the drug system (37 degrees C) and lowered the diffusivity of the drug in polymeric matrix and then the initial burst and fast diffusional release of captopril from commercial PLG were improved.

Biocompatible Materials↗
PubMedDate not supplied

Developing new methods for the treatment of malignant brain tumours: local delivery of anti-neoplastic agents using biodegradable polymers.

Controlled delivery of chemotherapeutic agents by biodegradable polymers is a new strategy that has been added to the arsenal available for the treatment of malignant neoplasms. This approach is particularly suitable for the management of brain tumours because of the constraints imposed by the blood brain barrier (BBB). The use of polymers for local drug delivery minimises systemic toxicity, while achieving prolonged elevation of intratumoural drug concentrations that results in improved efficacy. In addition, this strategy broadens the spectrum of drugs available for the treatment of neoplasms in the central nervous system to include agents whose efficacy is significantly limited by systemic toxicity or inability to penetrate the BBB. In this review, we discuss the rationale and background for the use of this novel approach. We also summarise the clinical trials and laboratory investigations leading to the development of local delivery of anti-neoplastic agents from biodegradable polymers for the treatment of malignant gliomas.

Animals↗
PubMed2004

Liposomes as adjuvant for anti-mycobacterial vaccine development.

Mycobacteria are intracellular pathogens that invade and reside inside the macrophages. Recent advances in controlled delivery systems for vaccines such as liposomes have sparked a renewed interest in their potential application for the prevention of mycobacterial infections. The versatility of liposomes in the incorporation of hydrophilic/hydrophobic components, their non-toxic nature, biodegradability, biocompatibility, adjuvanticity, induction of cellular immunity, property of sustained release and prompt uptake by macrophages, makes them attractive candidates for the delivery of antigens. This review focuses on liposome research in the area of mycobacterial diseases and highlights how the various mycobacterial components may be exploited as powerful antigens with liposomes as adjuvants.

Animals↗
PubMed2002

Tissue reaction and biodegradation of implanted cross-linked high amylose starch in rats.

The biocompatibility and degradation characteristics of cross-linked high amylose starch (Contramid were investigated in rats over 4 months. Contramid pellets (3-mm diameter and thickness) obtained by direct compression, were implanted subcutaneously and intramuscularly. On sequential time points, macroscopic observations of implantation sites were performed and tissue samples were removed, fixed, and histologically evaluated. No macroscopic inflammatory reaction was observed with Contramid.. Upon histologic examination, inflammatory reaction produced by Contramid was moderate and restricted to implantation sites. The sequence of inflammatory events with Contramid was similar regardless of implantation site. Degradation of Contramid pellets was characterized by fragmentation with formation of fibrovascular septa and phagocytosis by macrophages. Finally Contramid was mostly absorbed by the end of the 4-month period and substituted by adipocytes. It has been demonstrated that Contramid is a biocompatible and absorbable material.

Amylose↗
PubMed1987

Controlled release using a new bioerodible polyphosphazene matrix system.

Polyphosphazenes possess polymer backbones consisting of nitrogen and phosphorous formally separated by alternating single and double bonds. Their potential for biomedical applications stems from the fact that polymers with a wide array of properties can be synthesized using the same starting compound, poly(dichlorophosphazene), through changes in side chain substituents, and that many of these compounds synthesized have been found to biodegrade to harmless products. In this article, studies of a novel monolithic bioerodible polyphosphazene matrix system for controlled drug delivery are presented. Poly(imidazole methylphenoxy)phosphazene is synthesized and shown to be bioerodible. The versatility of drug delivery devices fabricated using this polymer is shown through studies of release of macro-molecules and low molecular weight drugs. Initial histological evaluations of this particular polyphosphazene are also presented.

Aniline Compounds↗
PubMed2006

In vitro and in vivo testing of bioabsorbable antibiotic containing bone filler for osteomyelitis treatment.

The use of local antibiotics from a biodegradable implant is appealing concept for treatment of chronic osteomyelitis. Our aim was to develop a new drug delivery system based on controlled ciprofloxacin release from poly(D/L-lactide). Cylindrical composite pellets (1.0 x 0.9 mm) were manufactured from bioabsorbable poly(D/L-lactide) matrix and ciprofloxacin (7.4 wt %). In vitro studies were carried out to delineate the release profile of the antibiotic and to verify its antimicrobial activity by means of MIC testing. A long-term study in rabbits was performed to validate the release of ciprofloxacin from the composite in vivo. Therapeutic level of ciprofloxacin (>2 microg/mL) was maintained between 60 and 300 days and the concentration remained below the potentially detrimental level of 20 microg/mL in vitro. The released ciprofloxacin had retained its antimicrobial properties against common pathogens. In an exploratory long-term in vivo study with three rabbits, ciprofloxacin could not be detected from the serum after moderate filling (160 mg) of the tibia (follow-up 168 days), whereas after high dosing (a total dose of 1,000 mg in both tibias) ciprofloxacin was found temporarily at low serum concentrations (14-34 ng/mL) during the follow-up of 300 days. The bone concentrations of ciprofloxacin could be measured in all samples at 168 and 300 days. The tested copolylactide matrix seems to be a promising option in selection of resorbable carriers for sustained release of antibiotics, but the composite needs modifications to promote ciprofloxacin release during the first 60 days of implantation.

Absorbable Implants↗
PubMed2004

Design of polyrotaxanes as supramolecular conjugates for cells and tissues.

This research focuses on the supramolecular challenge of enhancing multivalent binding between ligands and proteins or biological receptors on cell surfaces. Our special interest is using supramolecular-structured polymers, namely, polyrotaxanes consisting of ligand-immobilized alpha-cyclodextrins (alpha-CDs) threaded onto a poly(ethylene glycol) (PEG) chain capped at both terminals with bulky end groups via biodegradable linkages. The structural characteristics of these polyrotaxanes involve sliding and rotational motion of the ligands immobilized on alpha-CDs along a PEG chain, thus facilitating access to binding sites on proteins. This approach provides a novel biomaterial design in the field of drug delivery and tissue engineering.

Animals↗
PubMed2004

Incorporation of biodegradable nanoparticles into human airway epithelium cells-in vitro study of the suitability as a vehicle for drug or gene delivery in pulmonary diseases.

PURPOSE: Nanoparticles are able to enhance drug or DNA stability for purposes of optimised deposition to targeted tissues. Surface modifications can mediate drug targeting. The suitability of nanoparticles synthesised out of porcine gelatin, human serum albumin, and polyalkylcyanoacrylate as drug and gene carriers for pulmonary application was investigated in vitro on primary airway epithelium cells and the cell line 16HBE14o-. METHODS: The uptake of nanoparticles into these cells was examined by confocal laser scan microscopy (CLSM) and flow cytometry (FACS). Further the cytotoxicity of nanoparticles was evaluated by an LDH-release-test and the inflammatory potential of the nanoparticles was assessed by measuring IL-8 release. RESULTS: CLSM and FACS experiments showed that the nanoparticles were incorporated into bronchial epithelial cells provoking little or no cytotoxicity and no inflammation as measured by IL-8 release. CONCLUSIONS: Based on their low cytotoxicity and the missing inflammatory potential in combination with an efficient uptake in human bronchial epithelial cells, protein-based nanoparticles are suitable drug and gene carriers for pulmonary application.

Biodegradation, Environmental↗
PubMed2004

Synthesis, characterization and in vitro degradation of a biodegradable elastomer.

An elastomer was prepared from biodegradable components as a potential biomaterial for drug delivery and tissue engineering applications. The elastomer was synthesized in two steps. First, a star copolymer (SCP) was manufactured via ring opening polymerization of -caprolactone (epsilon-CL) with D,L-lactide using glycerol as initiator and stannous 2-ethylhexanoate as catalyst. This living SCP was further reacted with different ratios of a crosslinking monomer, 2,2-bis(epsilon-CL-4-yl)-propane in the presence of epsilon-CL as a solvent and co-monomer. The elastomers had very low glass transitions (-32 degrees C), sol contents ranging from 17% to 37%, and were soft and weak with physical properties similar to those of natural elastomers such as elastin. The physical properties decreased in a logarithmic fashion with time when degraded in phosphate buffered saline, indicative of first-order degradation kinetics. The elastomers degraded relatively slowly, with degradation being incomplete after 12 weeks.

Biocompatible Materials↗
PubMed1998

Protein release from polyphosphazene matrices.

Polyphosphazenes have been exploited as carriers for protein delivery due to versatility of molecular structures and sophisticated spectrum of chemical and physical properties. Ease of structural manipulations for this class of organometallic polymers allows efficient control over physico-chemical parameters of polyphosphazenes including their biodegradability and matrix permeability. Some polyphosphazenes offer additional advantages as protein delivery vehicles since microencapsulation of substrates in these systems can be achieved under remarkably mild physiological conditions. Because of these properties polyphosphazenes have tremendous potential as matrices for protein release as shown by studies both in vitro and in vivo.

Journal Article↗
PubMed2001

Development and characterization of cross-linked poly(malate) microspheres with dipyridamole.

Biodegradable cross-linked microspheres containing up to 63 wt.% of the active substance were obtained in a polycondensation process between D,L-malic acid and the tetrahydroxy compound dipyridamole. The in vitro release mechanism from biodegradable cross-linked microspheres has been studied. It was found that dipyridamole was released due to two-step hydrolysis of the ester bonds of the network. Initially, the only product of the hydrolytic degradation was found to be an oligomeric ester fraction with M(w)=1000 Da. The release of the free drug started after 8 days due to a further hydrolysis of the oligomers in solution. It was found that blood plasma enzymes in rats did not affect the hydrolytic processes. Biodegradable poly(malate) microspheres containing an anti-aggregating agent dipyridamole can be considered as a novel drug delivery system for a prolonged period of time implying a future parenteral application.

Animals↗
PubMedDate not supplied

Tunable DNA release from cross-linked ultrathin DNA/PLL multilayered films.

A novel ultrathin enzymatically degradable multilayered film using DNA as building blocks was fabricated by the layer-by-layer (LbL) technique. The UV-vis spectrometry and AFM experiments showed that the buildup of DNA and poly-L-lysine (PLL) was a kind of "exponentially growing films". The dye adsorption experiment suggested that the DNA molecules in the multilayered films were effectively protected by PLL. The films were further cross-linked by glutaraldehyde (GA). The cross-linking density of the films was modulated through the simple controlling of the time of the GA incubation process. An in vitro enzymatic degradation was carried out to investigate the DNA release profiles. The UV-vis spectrometry and fluorescence measurements indicated that the DNA release profiles were accordingly changed with the cross-linking density of the films. The nanoscale, easily processed enzymatically biodegradable PLL/DNA film with the ability to precisely control DNA release profiles may serve as a novel DNA delivery system, which may have great potential for gene therapy applications in implantable materials and biomedical devices.

Cross-Linking Reagents↗
PubMed1999

Biocompatible magnetic polymer carriers for in vivo radionuclide delivery.

The magnetic guidance of antiplastic and antibacterial agents as well as x-ray and MRI contrast substances in vivo by means of magnetic particles has been attempted repeatedly during the last 2 decades with more or less success. When using microparticles, the circulation time in the blood, the biodistribution, and to a greater or lesser extent, the specific targeting are determined by the uniformity of size, chemical composition, surface modification, and the electric surface charge. The electrophoretic mobility is an important parameter for the prediction of the usefulness of the prepared particle, modified by chemical and biological molecules. For its success, radionuclide therapy depends on the critical relationship between the amount of radioactive isotopes in the target tissue and in critical normal tissue. Because the implementation of radioimmunotherapy for the treatment of cancer has proven to be considerably more difficult than initially anticipated, we propose the use of magnetic nanospheres for the well directed delivery of radionuclides to a tumor after the intravenous administration of the biodegradable colloidal suspension.

Biocompatible Materials↗
PubMed2005

Local antibiotic delivery vehicles in the treatment of musculoskeletal infection.

The primary benefit achieved with local antibiotic delivery vehicles is the ability to obtain extremely high levels of local antibiotics without increasing systemic toxicity. Antibiotic-loaded bone cement represents the current standard as an antibiotic delivery vehicle in orthopaedic surgery. Biodegradable alternatives to antibiotic-loaded bone cement also are being used clinically and there are many new products in the active stages of development. These alternatives can be categorized as bone graft, bone graft substitutes or extenders, natural polymers (protein-based products), and synthetic polymers. Composite biomaterials that simultaneously provide the functions of variable antibiotic delivery patterns and also contribute to the process of bone regeneration represent the most ideal class of local antibiotic delivery vehicles. High concentrations of certain antibiotics have been shown to affect the process of normal bone regeneration adversely in a dose dependent response. Considerable investigation still is required to determine the proper use of locally administered antibiotics to negotiate the balance between eradicating infection without excessively inhibiting the processes of bone regeneration.

Anti-Bacterial Agents↗
PubMed2003

Selective adipose tissue ablation by localized, sustained drug delivery.

The reduction of adipose depots is widely considered to be the optimal approach to limit pathologies associated with obesity. While many current antiobesity strategies are centered on regulating satiety, these approaches typically attempt an overall weight loss and are unable to target distinct adipose depots specifically associated with disease risk. The authors report a novel therapeutic modality utilizing localized and sustained delivery of drugs to provide for the selective ablation of adipose tissue. Using the epididymal fat pad of Sprague-Dawley rats as a model, they injected into the tissue poly(lactide-co-glycolide) microspheres encapsulating tumor necrosis factor-alpha, a well-known regulator of adipose tissue mass. The utility of this approach was investigated in vivo by measuring the fat pad mass relative to the contralateral control within the same animal (n = 4 at each time point) and in vitro by measuring apoptosis in adipose organ cultures. The authors demonstrated control over the localization of tumor necrosis factor-alpha by performing blood analysis. This is the first report of localized drug delivery for adipose tissue ablation, and these results indicate the potential utility of the general tissue ablation approach for treatment of numerous pathologies.

Adipose Tissue↗