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Results for “Biodegradable Delivery Systems”

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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↗
PubMed2006

Self-exploding lipid-coated microgels.

Self-exploding microparticles show potential for advanced delivery of certain therapeutics. This study evaluates (1) whether degrading biodegradable dextran hydroxyethyl methacrylate (dex-HEMA) microgels can be coated by a lipid membrane and (2) whether the surrounding membrane can be ruptured by the increasing swelling pressure of the degrading microgel. We found that adsorption of charged liposomes to oppositely charged dex-HEMA microgels provides efficient coating of the microgels, whereby microparticles with a "core-shell" structure were clearly obtained. Especially, we could confirm experimentally that the swelling pressure increase of degrading dex-HEMA microgels can destroy the lipid membrane surrounding the microgels.

Adsorption↗
PubMed2003

Gene transfer occurs with enhanced efficiency in biofilms and induces enhanced stabilisation of the biofilm structure.

There has been much interest in bioremediation based on the introduction of bacteria able to catabolise recalcitrant compounds deposited in the environment. In particular, the delivery of catabolic information in the form of conjugative plasmids to bacterial populations in situ has great potential. As most bacteria in the environment live in surface-associated communities (biofilms), the gene transfer systems within these communities need to be better characterised for bio-enhancement strategies to be developed. Recent findings suggest that gene transfer does take place within biofilms, but studies also identified limitations and bottlenecks of the process. The dense population structure in biofilms increases plasmid dispersal by conjugation, and the conjugation mechanism itself may stimulate biofilm development. Moreover, DNA release and transformation seem to be part of a biofilm-related life cycle and released DNA stabilises the biofilm structure. Both of these gene-transfer mechanisms may be autocatalytically promoted in biofilms, presenting new possibilities for efficient bio-enhancement strategies.

Bacteria↗
PubMed2005

[Biodegradable polymers for colon-specific drug delivery].

This review focuses on the colonic drug delivery, especially using biodegradable polymers i.e. guar gum, chondroitin sulfate, pectin, starch and amylose, dextran, chitosan, inulin. Basics of colon-specific targeting, formulation aspects, microflora influence and application of cross-linking techniques and polymer mixtures for targeting drugs into the colon are presented. Adventages and disadventages of colon-specific drug delivery are also described. A number of polymers is important in the context of colon-specific drug delivery. Considerable progress has been made over last three decades in this area. Although extensive investigations have to be done in the area of microflora endogenous ecosystems and enzymatic science, immunoactivity of biopolymers, and absorption enhancers for colonic mucous. Completely synthetic polymers of good swelling properties and sensitive to bacterial enzymes are also possible in the close future.

Absorbable Implants↗
PubMed2001

[Research and application of drug controlled release technique in tissue engineering].

OBJECTIVE: To investigate protection of biological activity and controlled release of growth factor by means of drug controlled release technique in tissue engineering. METHODS: Using drug controlled release technique that to embed or microcapsulate the biological drug with biodegradable polymer. RESULTS: The aliphatic polylactone could be used as drug carrier for each drug including the biological matter. And the release behavior of the drug could be controlled by adjusting the molecular structure of the carrier and the controlled release method. The successful example, that to realize regeneration of rat's sciatic nerve with 5, 10, 15 and 20 mm of gap by using polylactide as nerve guide and the embedding growth factor, had been obtained. CONCLUSION: It is possible to realize protection of biological activity and sustained release of growth factor by using aliphatic polylactone as drug carrier.

Adenosine↗
PubMed1999

Evaluation of the efficacy of a bioerodible bupivacaine polymer system on antinociception and inflammatory mediator release.

Pain due to tissue injury is often characterized by the presence of hyperalgesia and allodynia. It is hypothesized that these perceptual states are mediated by sensitization of peripheral terminals of primary afferent neurons together with several changes in the central nervous system. This provides a rationale for preemptive analgesia, whereby the blockade of primary afferent input prior to injury may result in a reduction of post-injury pain. One approach for prolonged blockade of primary afferent input is the use of bioerodible polymer systems providing regulated release of local anesthetics. Bioerodible polymer systems offer the theoretical advantage of controlled drug delivery maintained over prolonged periods. Local application of this system to the inflamed tissue compartment permits the use of smaller total drug doses. This may minimize systemic side effects, while maintaining prolonged peripherally-mediated antinociception. In the present study, we evaluated the effects of a bioerodible polymer/bupivacaine system (PLGA/bupivacaine) on several indices of inflammation and on hindpaw levels of the inflammatory mediators, substance P and bradykinin in the complete Freund's adjuvant model. We observed that PLGA/bupivacaine reduces inflammatory hyperalgesia, edema and hyperthermia in a temporal and dose-related fashion in awake animals. Moreover, we demonstrated that PLGA/bupivacaine has a prolonged inhibitory effect on the tissue levels of substance P and bradykinin in the inflamed hindpaws. The results of these studies clearly indicate the potential therapeutic utility of the PLGA bupivacaine system, with the single dose administration producing a prolonged suppression of hyperalgesia, edema and biochemical indices of inflammation.

Anesthetics, Local↗
PubMedDate not supplied

Surface-modified and conventional nanocapsules as novel formulations for parenteral delivery of halofantrine.

The aim of this work was to develop a stable injectable formulation of the antimalarial drug halofantrine (Hf) based on nanocapsules (NC) prepared from biodegradable polymers with Miglyol 810N as the oily core. Poly(D,L-lactide) PLA and its copolymers with poly(ethyleneglycol) (PLA-PEG) were used together with the surfactants poloxamer 188 and lecithin to yield NC with different surface properties. Highly efficient loading of the free base form of Hf was obtained; zeta potential measurements indicated that a part of the associated Hf was at the NC surface, interacting with the lecithin. NC were 150-250 nm in diameter and more stable on storage than nanoemulsions formed from oil and lecithin without polymer. The most stable NC, showing minimal size changes and flocculation, were those with a high density of 20-kDa PEG chains covalently grafted at the surface. Hf release from NC occurred mainly by partition with the external medium. In PBS, even when Tween 80 was added, release was limited to 20% of the total content, whatever the formulation. Addition of serum to the medium allowed complete and rapid release from PLA NC stabilized with adsorbed poloxamer 188, because of the high affinity of Hf for lipoproteins. However, the presence of covalently grafted PEG chains at the surface limited release by providing a hydrophilic steric barrier at the particle surface. A dense coverage with long PEG chains provided the best reduction of release. Such systems could constitute a long-circulating intravenous formulation of Hf for treating severe malaria.

Antimalarials↗
PubMed2005

Tailor-made polymers for local drug delivery: release of macromolecular model drugs from biodegradable hydrogels based on poly(ethylene oxide).

Hydrogels were synthesized from degradable and non-degradable PEO bismacromonomers. The degradability was provided by hydrolyzable segment between the main PEO chain and the methacrylate or methacrylamide groups at the both PEO chain termini. The hydrolyzable segment consisted of a monomeric alpha-hydroxy acid or a depsipeptide. The polymerization conditions and the choice of a bismacromonomer influenced the cross-linking density of the hydrogels. The release behavior of model macromolecular solutes, FITC dextran and bovine serum albumin (BSA), was studied. The small FITC-dextran 4 kDa was released rapidly from the hydrogel. The larger FITC-dextran 40 kDa and BSA were retained inside the matrix and their release rate was controlled by the degradation.

Biocompatible Materials↗
PubMed2003

Surfactant-free, biodegradable nanoparticles for aerosol therapy based on the branched polyesters, DEAPA-PVAL-g-PLGA.

PURPOSE: This study describes the development of surfactant-free, biodegradable nanoparticle systems with varying physicochemical properties and their suitability for pulmonary application via nebulization. METHODS: Nanoparticle suspensions were formulated from the branched polyester, diethylaminopropyl amine-poly(vinyl alcohol)-grafted-poly(lactide-co-glycolide) (DEAPA-PVAL-g-PLGA) alone, as well as with increasing amounts of carboxymethyl cellulose (CMC). Particle size, zeta potential, turbidity, and morphology (atomic force microscopy) were characterized. Three formulations were chosen for further study: Cationic nanoparticles without CMC, cationic nanoparticles with CMC, and anionic nanoparticles with an excess of CMC. Nanoparticle degradation was characterized, as well as stability during nebulization. Nanoparticle-cell interactions were investigated and quantified using confocal laser scanning microscopy and fluorescence spectrometry. RESULTS: Nanoparticles ranged in size from 70-250 nm and displayed zeta potentials of +58.9 to -46.6 mV. Anionic nanoparticles showed the highest stability during nebulization. The degradation rate of each nanoparticle formulation decreased with increasing amounts of CMC. Cell association was highest among cationic nanoparticles (57% and 30%, respectively), although these were not internalized. Despite a lower rate of cell association (3%), anionic nanoparticles were internalized by A549 cells. CONCLUSIONS: Surfactant-free nanoparticles from DEAPA-PVAL-g-PLGA are versatile drug delivery systems; however, only the anionic formulations investigated were proven suitable for aerosol therapy.

Aerosols↗
PubMed2006

Formulation of anastrozole microparticles as biodegradable anticancer drug carriers.

The purpose of this study was to develop poly(d,l-lactic-co-glycolic acid) (PLGA)-based anastrozole microparticles for treatment of breast cancer. An emulsion/extraction method was used to prepare anastrozole sustained-release PLGA-based biodegradable microspheres. Gas chromatography with mass spectroscopy detection was used for the quantitation of the drug throughout the studies. Microparticles were formulated and characterized in terms of encapsulation efficiency, particle size distribution, surface morphology, and drug release profile. Preparative variables such as concentrations of stabilizer, drug-polymer ratio, polymer viscosity, stirring rate, and ratio of internal to external phases were found to be important factors for the preparation of anastrozole-loaded PLGA microparticles. Fourier transform infrared with attenuated total reflectance (FTIR-ATR) analysis and differential scanning calorimetry (DSC) were employed to determine any interactions between drug and polymer. An attempt was made to fit the data to various dissolution kinetics models for multiparticulate systems, including the zero order, first order, square root of time kinetics, and biphasic models. The FTIR-ATR studies revealed no chemical interaction between the drug and the polymer. DSC results indicated that the anastrozole trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. The highest correlation coefficients were obtained for the Higuchi model, suggesting a diffusion mechanism for the drug release. The results demonstrated that anastrozole microparticles with PLGA could be an alternative delivery method for the long-term treatment of breast cancer.

Anastrozole↗
PubMed2000

Drug release characteristics of unimolecular polymeric micelles.

Biodegradable, unimolecular polymeric micelles possess several features that are attractive for drug delivery applications: Thermodynamic stability, ability to encapsulate and solubilize a hydrophobic guest molecule, biodegradability, as well as size and surface characteristics that prevent rapid clearance by the RES. Here we investigate the potential of these unimolecular polymeric micelles to release a drug for an extended time. Lidocaine was used as a model drug for in vitro studies using a horizontal diffusion cell and cellulose membrane that prevented polymer transport from the source to the receiver compartment. The transport of free lidocaine from source to receiver under sink conditions was zero-order and complete within 8 h. The transport of lidocaine initially encapsulated in polymer was zero-order for the first 14 h, and 96% of the lidocaine was detected within 24 h.

Diffusion↗
PubMed2004

Effect of the size of biodegradable microparticles on drug release: experiment and theory.

The aim of this study was to investigate the effect of the size of biodegradable microparticles (monolithic dispersions) on the release rate of an incorporated drug in a quantitative way. 5-Fluorouracil-loaded, poly(lactic-co-glycolic acid)-based microparticles were prepared with a solid-in-oil-in-water solvent extraction technique. In vitro drug release from different-sized particle fractions was measured in phosphate buffer pH 7.4. Differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and size exclusion chromatography (SEC) were used to monitor the degradation behavior of the polymer and morphological changes of the microparticles upon exposure to the release medium. Based on these experimental results, an appropriate mathematical theory was identified and used to get further insight into the underlying physical and chemical processes, which are involved in the control of drug release. Interestingly, the relative as well as the absolute release rate of the drug increased with increasing microparticle radius, despite of the increasing diffusion pathways. SEC, DSC and SEM analysis revealed that the degradation behavior of the matrix forming polymer was not significantly affected by the size of the devices and that autocatalytic effects do not seem to play a major role. Importantly, the initial drug loading significantly increased with increasing radius of the drug delivery system. Thus, large microparticles became more porous during drug release than small microparticles, leading to higher apparent diffusivities and drug transport rates. This effect overcompensated the effect of the increasing diffusion pathways with increasing microparticle radius, resulting in increased drug release rates with increasing device dimension. The applied mathematical model, considering drug diffusion with non-constant diffusivities (to account for polymer degradation) was able to quantitatively describe the observed drug release patterns. Importantly, an exponential relationship could be established between the diffusion coefficient and the initial loading of the drug. Based on this dependency, it was possible to predict the resulting drug release kinetics for arbitrary microparticle sizes in a quantitative way.

Biotransformation↗
PubMedDate not supplied

Fully degradable hydrophilic polyals for protein modification.

Modification of proteins with hydrophilic polymers is an effective strategy for regulation of protein pharmacokinetics. However, conjugates of slowly or non-biodegradable materials, such as poly(ethylene glycol), are known to cause long-lasting cell vacuolization, in particular in renal epithelium. Conjugates of more degradable polymers, e.g., polysaccharides, have a significant risk of immunotoxicity. Polymers that combine complete degradability, long circulation in vivo, and low immuno and chemical toxicity would be most beneficial as protein conjugate components. This study explores new fully biodegradable hydrophilic polymers, hydrophilic polyals. They are nontoxic, stable at physiological conditions, and undergo proton-catalyzed hydrolysis at lysosomal pH. The model enzyme-polyal conjugates were prepared with 61-98% yield using conventional and novel conjugation techniques and retained 90-95% of specific activity. The model conjugates showed a significant prolongation of protein circulation in rodents, with a 5-fold reduction in the renal accumulation. The data suggests that hydrophilic polyals may be useful in designing protein conjugates with improved properties.

Animals↗
PubMed2003

Biodegradable intrascleral implant for sustained intraocular delivery of betamethasone phosphate.

PURPOSE: To evaluate the feasibility of using a biodegradable intrascleral implant for intraocular sustained delivery of betamethasone phosphate (BP). METHODS: The intrascleral implant (0.5 mm thick and 4 mm in diameter) was made of poly(DL-lactide) containing 25% betamethasone phosphate. The in vitro release of BP from the implant was evaluated by high-performance liquid chromatography (HPLC). The implants were placed into a scleral pocket in the rabbit's eye. The concentrations of BP in the aqueous humor, vitreous, and retina-choroid were measured by HPLC. The toxicity and biocompatibility of the implant were evaluated by slit lamp examination, electroretinography, and light microscopy. RESULTS: In vitro studies demonstrated that the implants released BP in a biphasic pattern for at least 8 weeks. The BP concentrations in the vitreous and the retina-choroid remained within the concentration range capable of suppressing inflammatory responses for more than 8 weeks. The BP concentration was greater in the retina-choroid than in the vitreous. In the aqueous humor, BP was below the detection limit during the observation period. No significant toxicity to the retina was observed. Also, the implant showed good biocompatibility in the eye. CONCLUSIONS: These results suggest that the intrascleral implant would be a promising system for delivery of steroid to the posterior segment of the eye.

Absorbable Implants↗
PubMed1991

Structural and microbiological evaluation of a degradable sustained-release device for use in periodontal therapy.

Degradable protein matrices containing chlorhexidine were tested as intra-pocket drug delivery systems in the treatment of periodontal diseases. The properties of the device were mainly dependent upon the degree of cross linking in the matrix, which could be varied according to the preparative conditions. The degree of cross linking was determined by amino acid analysis based on the amount of free lysine in the protein. The release of chlorhexidine and of the plasticizer used in the preparation of the matrix were determined. The release of chlorhexidine from the matrix was prolonged for a period of 300 hours, and the release of plasticizer ceased after four hours. Limited clinical trials suggest that one of the degradable devices--that containing the highest amount of cross-linking--causes a significant reduction in the amount of perio-pathogenic bacteria following its insertion into the periodontal pockets of patients with periodontal disease.

Adult↗
PubMed1996

Adhesion prevention with ancrod released via a tissue-adherent hydrogel.

The objective of this investigation was to evaluate the effect of ancrod, a fibrinogenolytic protease from Malayan pit viper venom, locally delivered through a photopolymerized biodegradable hydrogel in preventing postoperative adhesions. The experimental model involved ischemic and serosal injury to the uterine horns of rats with measurement of adhesions 7 days after injury. Ancrod was delivered intravenously for 5 days preoperatively through 3 days postoperatively, intraperitoneally for 5 days preoperatively, intraperitoneally for 3 days postoperatively, and locally via the hydrogel formed upon the uterine horns by photopolymerization of an aqueous precursor solution. Systemic defibrinogenation by intravenous administration pre-through postoperatively reduced the extent of adhesions by 63% without dose sensitivity from 5 to 20 units/kg/day. Preoperative defibrinogenation by intraperitoneal administration reduced adhesion extent by up to 57%, while postoperative administration was more effective, reducing adhesions by up to 84% with a dose-dependent response from 5 to 20 units/kg/day. Administration of ancrod by local release from a tissue-adherent hydrogel was more effective than either the hydrogel alone or the same amount of ancrod administered by postoperative intraperitoneal injection. Adhesions were reduced by 82% at a local dose of 10 units/kg, compared to a reduction of 68% due to the barrier properties of the gel alone (P < 0.01) and of 19% due to the same amount of drug given at the time of surgery (P < 0.001). Local delivery of ancrod from a tissue-adherent hydrogel barrier thus provided an efficacious prevention to postoperative adhesions while permitting administration of a low total dose of the protease.

Abdomen↗
PubMed2005

Selective targeting of antibody-conjugated nanoparticles to leukemic cells and primary T-lymphocytes.

In the present study, surface-modified nanoparticles based on biodegradable material were used for antibody coupling in order to get a selective drug carrier systems. Gelatin nanoparticles were prepared by a desolvation process. Sulfhydryl groups were introduced which enabled the linkage of NeutrAvidin (NAv). Antibodies specific for the CD3 antigen on lymphocytic cells were conjugated to the nanoparticles surface. The binding of biotinylated anti-CD3 antibody was achieved by NAv-biotin-complex formation. Cellular binding and uptake were determined by flow cytometry and confocal laser scanning microscopy (CLSM). Cell-type-specific targeting of anti-CD3-conjugated nanoparticles into CD3-positive human T-cell leukemia cells and primary T-lymphocytes could be shown. Celluar uptake and effective internalization of antibody-conjugated nanoparticles into CD3 expressing cells were demonstrated. Uptake rates of about 84% into T-cell leukemia cells were observed. To confirm selectivity of T-cell targeting, competition experiments were carried out adding excessive free anti-CD3 prior to nanoparticle incubation leading to significantly reduced cellular uptake of antibody-conjugated nanoparticles. Further analysis on the mechanism of uptake confirmed a receptor-mediated endocytotic process. Protein-based nanoparticles conjugated with an antibody against a specific cellular antigen hold promise as selective drug delivery systems for specific cell types.

Antibodies↗
PubMed2005

Biphenyl degradation kinetics by Burkholderia xenovorans LB400 in two-phase partitioning bioreactors.

Biphenyl could be successfully degraded by Burkholderia xenovorans LB400, initially described as Pseudomonas sp. LB400, in two-phase partitioning bioreactors (TPPBs). TPPBs are comprised of an aqueous, cell containing phase, and an immiscible, biocompatible organic phase that partitions toxic and/or poorly soluble substrates (in this case biphenyl) based on maintaining a thermodynamic equilibrium. The critical LogKO/W of the organism was found to be approximately 5.5, indicating that solvents with a LogKO/W larger than 5.5 are suitable as delivery phases for B. xenovorans LB400. Two solvents selected for the TPPB system were octadecene and bis(2-ethylhexyl)sebacate (BES). In one experiment a total of 6.6 g biphenyl per l aqueous-phase-equivalent (biphenyl delivered in solvent, at an aqueous phase to solvent ratio of 10) could be degraded in 25 h during batch operation with octadecene. The specific growth rate and the half saturation constant of the Monod model were estimated to be mumax=0.25 h-1 and KS=0.0001 g l-1, and the yield coefficient was YX/S=0.48 g biomass per g biphenyl. These parameter estimates were used to predict the time course of biphenyl degradation at different initial substrate concentrations and with biphenyl delivered from the two solvents with different partitioning behaviour for biphenyl. The predictions were validated by experimental data, confirming the microbial kinetics as well as the expected partitioning effects.

Biodegradation, Environmental↗