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Results for “Biodegradable Delivery Systems”

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PubMed2006

Drug delivery from ocular implants.

Developing an intraocular drug delivery system (DDS) is urgently needed because most vitreoretinal diseases are refractory to conventional pharmacological approaches; eye drops and systemically administered drugs cannot deliver therapeutic drug concentrations into vitreoretinal tissue. Intraocular DDSs address this problem. Intraocular sustained-drug release via implantable devices or injectable microparticles has been investigated to treat vitreoretinal diseases. A nonbiodegradable implant was first used in 1996 for cytomegalovirus retinitis secondary to the acquired immunodeficiency syndrome. Biodegradable implants, composed of hydrophilic or hydrophobic polymers, in the shape of rods, plugs, discs or sheets have been investigated. An injectable rod is presently being assessed in a Phase III trial to treat macular oedema secondary to diabetic retinopathy or branch-retinal vein occlusion. Intraocular DDSs using a biodegradable implant may soon be successfully used to treat serious intraocular disorders.

Animals↗

PubMed2001

In vivo response to biodegradable controlled antibiotic release systems.

In this study, the major goal was to evaluate in vitro and in vivo findings by macroscopy, radiology, and histology to determine the effectiveness of therapy of experimental implant-related osteomyelitis with antibiotic carrier rods constructed of microbial polyesters. The polymers used were poly(3-hydroxybutyrate-co-4-hydroxyvalerate) [P(3-HB-co-4-HB)] and poly(3-hydroxybutyrate-co-3-hydroxy- valerate) [P(3-HB-co-3-HV)]. Both the Sulperazone and the Duocid-P(3-HB-co-4-HB) rods with a drug to polymer ratio of 1:1 (w/w) were effective in treating the bone infection that was experimentally initiated by inoculation of a hemolytic strain of Staphylococcus aureus (coagulase positive; phage type 52/52b) together with metal implants into the medullary area of rabbit tibia. Macroscopical data revealed that the effectiveness of therapy was apparent at week 6 for all categories tested. Radiological findings with Duocid- and Sulperazone-loaded P(3-HB-co-4-HB) rods improved significantly when judged by changes in periosteal elevation, widening of bone shaft, new bone formation, and soft-tissue deformation after 6 weeks of implantation. Histologically the signs of infection were found to subside by weeks 3 and 6. Inflammatory cells were replaced with bone-forming cells upon treatment with Sulperazone-P(3-HB-co-4-HB) and Duocid-P(3-HB-co-4-HB). Osteoblastic activity was prominent. Intramedullary inflammation, although still present, started to be replaced by fibrous or bony tissue. Histological findings presented the subsidence of infection. In summary, the antibiotic-loaded biopolymeric rods appeared to have potential as a new controlled-release system for the treatment of implant related osteomyelitis and chronic osteomyelitis.

Animals↗

PubMed2003

Biodegradable polymer-mediated intratumoral delivery of cisplatin for treatment of human head and neck squamous cell carcinoma in a chimeric mouse model.

BACKGROUND: The effectiveness of chemotherapeutic agents is proportional to the dose of the agents at their targets; however, the dose is limited by systemic toxicity. Attempts have been made to improve therapeutic effectiveness by increasing maximum tolerated dose (MTD) of chemotherapeutic agents using various local and regional drug delivery systems. Herein we report the use of an injectable biodegradable polymer to deliver cisplatin for intratumoral treatment of human head and neck squamous cell carcinoma (HNSCC) in a chimeric mouse model. The objectives of this research project were (1) to determine the release kinetics of cisplatin from the polymer delivery system, (2) to identify the MTD of polymer-delivered cisplatin, and (3) to evaluate its therapeutic efficacy. METHODS: To determine the in vivo release kinetics, cisplatin-loaded polymer was injected subcutaneously into rats. Implants were removed and analyzed for remaining cisplatin by a high-performance liquid chromatography technique. Sera from these rats were assayed for platinum by atomic absorption spectrophotometry. For MTD determination, SCID mice were engrafted subcutaneously with fresh biopsy specimens of HNSCC. Various doses of free or polymer-loaded cisplatin were injected intratumorally. MTD was estimated based on the threshold at which all mice survived. The antitumor efficacy of free and polymer-loaded cisplatin at their respective MTD was assayed on the same chimeric mouse model. RESULTS: The polymer delivery system released 80% of the loaded cisplatin in vivo over a 7-day period. The polymer-delivered cisplatin exhibited higher MTD (36 mg/kg) than free cisplatin (18 mg/kg) and had a statistically significant tumor suppression effect compared with free cisplatin when used at their respective MTD. CONCLUSIONS: The polymer delivery system can sustain cisplatin release for a period of 7 days. It can increase MTD and potentially enhance the antitumor efficacy of cisplatin against human head and neck cancers.

Animals↗

PubMed2005

Exploiting receptor biology for oral vaccination with biodegradable particulates.

The effective delivery of antigens via the oral route is an extremely desirable goal. Mucosal delivery of antigens stimulates mucosal and systemic immunity without affecting maternal antibodies and reduces the need for sterile needles or trained personnel. To date, there are very few commercially available oral vaccines and despite numerous reports in the scientific literature to show the success of biodegradable antigen carriers, none of these have achieved commercial status. Nevertheless, many studies have shown the great potential of biodegradable antigen carriers for oral vaccination in preclinical studies, but a more rational approach may be to specifically target antigen-loaded biodegradable microspheres to cells in the mucosal immune system which transport and process antigens for T cell recognition. Modern cell and molecular biology techniques have unearthed a wealth of information regarding important receptors involved in the capture of luminal antigens by microfold or membranous (M) cells and receptors on dendritic cells (DCs) which may allow future targeting of antigens to specific DC phenotypes, thus directing the immune response appropriately. In this review, we consider the use of currently available biodegradable antigen carriers and speculate on how these may be improved to more efficiently target mucosal effector sites.

Administration, Oral↗

PubMed1975

Preparation and evaluation of a sustained naloxone delivery system in rats.

The use of a non-biodegradable polymer system to provide a sustained release of the narcotic antagonist naloxone in rats is described. The kinetics of morphine analgesia (measured by the hot-plate test) in the presence of the naloxone implant, and the urinary excretion of radiolabeled naloxone were measured. The shift of the morphine dose-response curve to the right is expressed in terms of dose ratios, which were calculated from the ED50 values for morphine obtained 9 days before, and 1, 8, 15, 22 and 29 days after implantation of the polymer. Our experiments indicate that effective levels of antagonist were maintained for 3-4 weeks after implantation of a polymer system containing 16 mg of naloxone. After 29 days, more than 95% of the absorbed drug had been released, with 16% of the implanted radioactivity appearing in the urine. These results demonstrate the feasibility of using a sustained release form of a narcotic antagonist to block the effects of morphine.

Animals↗

PubMed2003

Chitosan-based gastrointestinal delivery systems.

Chitosan, a natural polymer obtained by alkaline deacetylation of chitin, is non-toxic, biocompatible, and biodegradable. These properties make chitosan a good candidate for the development of conventional and novel gastrointestinal (GI) drug and gene delivery systems. The objective of this review is to summarize the recent applications of chitosan in oral and/or buccal delivery, stomach-specific drug delivery, intestinal delivery, and colon-specific drug delivery. The use of chitosan for targeting of drugs to each of these sites in the GI tract is illustrated by examples supported by in vivo studies. Chitosan appears to be a promising material for GI drug and gene delivery applications as many derivatives and formulations are being examined.

Animals↗

PubMedDate not supplied

Preparation and characterization of poly(D,L-lactic-co-glycolic Acid) microspheres containing flurbiprofen sodium.

This study aimed to prepare biodegradable microspheres containing flurbiprofen sodium, a nonsteroidal anti-inflammatory drug (NSAID), as the drug delivery system to the periodontal pocket. Microspheres were prepared from biodegradable copolymers of poly (D,L-lactic-co-glycolic acid) (PLGA) using solvent evaporation method. The effects of the different copolymers and amounts of polyvinyl alcohol (PVA) as a dispersing agent on characteristics of the microspheres were evaluated. Although there was no correlation between microsphere size and amount of PVA, an optimum PVA concentration was essential to achieve narrower size distributions of microspheres. As the concentration of PVA increased, the drug loading of the microspheres increased. The effect of PVA on drug loading was found to be statistically significant for those microspheres prepared from PLGA 50:50 (p < 0.05). Regarding copolymer composition, PLGA 85:15 provided higher drug loading into the microspheres than PLGA 50:50 (p < 0.05). The recoveries of microspheres (60-80%) were affected neither by different PVA concentrations nor by copolymer compositions (p > 0.05). According to the first-order release rate constants of the microspheres, the microspheres of PLGA 50:50 released the drug at the highest rate consistently, with the highest hydrophilicity of this copolymer.

Algorithms↗

PubMed2005

Local inner-ear drug delivery and pharmacokinetics.

Several drugs that are applied directly to the inner ear are in widespread clinical use for the treatment of inner-ear disorders. Many new substances and drug delivery systems specific to the inner ear are under development and in some cases are being evaluated in animal experiments and in clinical studies. However, the pharmacokinetics of drugs in the inner ear is not well defined and the field is plagued by technical problems in obtaining pure samples of the inner-ear fluids for analysis. Nevertheless, a basic understanding of the mechanisms of drug dispersal in the inner ear has emerged, which facilitates the design and interpretation of future pharmacokinetic studies.

Animals↗

PubMedDate not supplied

Polysaccharides for colon targeted drug delivery.

Colon targeted drug delivery has the potential to deliver bioactive agents for the treatment of a variety of colonic diseases and to deliver proteins and peptides to the colon for their systemic absorption. Various strategies, currently available to target the release of drugs to colon, include formation of prodrug, coating of pH-sensitive polymers, use of colon-specific biodegradable polymers, timed released systems, osmotic systems, and pressure controlled drug delivery systems. Among the different approaches to achieve targeted drug release to the colon, the use of polymers especially biodegradable by colonic bacteria holds great promise. Polysaccharidases are bacterial enzymes that are available in sufficient quantity to be exploited in colon targeting of drugs. Based on this approach, various polysaccharides have been investigated for colon-specific drug release. These polysaccharides include pectin, guar gum, amylose, inulin, dextran, chitosan, and chondroitin sulphate. This family of natural polymers has an appeal to drug delivery as it is comprised of polymers with a large number of derivatizable groups, a wide range of molecular weights, varying chemical compositions, and, for the most part, low toxicity and biodegradability yet high stability. The most favorable property of these materials is their approval as pharmaceutical excipients.

Animals↗

PubMed2005

Formulation aspects of biodegradable polymeric microspheres for antigen delivery.

Biodegradable microspheres (MS) have proven to be very useful antigen delivery systems that are ingested by immunocompetent cells and provide prolonged antigen release and lasting immunity thanks to sustained release of the microencapsulated material. This review provides an applicable summary of different formulation routes for the purpose of producing safe, qualified and efficacious products of microencapsulated peptide and protein antigens. We have brought to attention, with case examples, not only the most common means of improving the quality of microsphere formulations, i.e., the use of stabilising additives, but also less commonly known and applied approaches, e.g., ion pairing, novel polymer systems, solid-state and other innovative microencapsulation methods.

Antigens↗

PubMed2000

Biodegradable scleral implant for controlled intraocular delivery of betamethasone phosphate.

We evaluated nail-like, biodegradable scleral implants as a controlled intraocular delivery system of betamethasone phosphate (BP) for the treatment of chronic uveitis using pigmented rabbits. The scleral implants, which contained 10% and 25% of BP (weight 8.5 mg; length 5 mm), were made of poly (D,L-lactide-co-glycolide) (PLGA). In vivo release and retinal toxicity after implantation were also studied in pigmented rabbits. The in vitro release studies demonstrated the 10% and 25% BP-loaded scleral implants released BP in a biphasic release pattern for at least 1 month. The BP concentrations in the vitreous and the retina/choroid after application of scleral implants in pigmented rabbit eyes stayed within the concentration range capable of suppressing inflammatory responses for over 1 month. The BP concentration was greater in the retina/choroid than in the vitreous throughout the study. No substantial toxic reactions in the retina were observed by electroretinography. Our findings suggest that the BP-loaded scleral implant may be a promising device for treatment of chronic uveitis.

Animals↗

PubMed1995

Prolongation of epidural anesthesia in the rabbit with the use of a biodegradable copolymer paste containing lidocaine.

Prolongation of the drug effect using a drug-delivery system has recently been introduced in local anesthesia. In this study, we investigated the prolonging effect of an epidurally injected biodegradable copolymer paste containing 10% lidocaine (Lid-CoPol). Twenty-nine rabbits were studied. A catheter was placed in the epidural space at the level of L6-7 in each animal. A solution of 10% lidocaine (Group I, n = 12), or a copolymer containing 10% lidocaine (Lid-CoPol), (Group II, n = 12) or copolymer paste only (Group III, n = 5) was injected epidurally at a dose of 0.15 mL/kg. The effect of each drug was assessed by evaluation of response to pain stimulation and of the degree of motor block produced. The plasma lidocaine concentration was also measured consecutively in five animals of both Groups I and II. The duration of sensory and motor block of Lid-CoPol was 800% and 975% longer, respectively, than that of plain lidocaine solution. Plasma lidocaine concentration reached a maximum 5 min after injection (5.5 +/- 0.5 micrograms/mL) in Group I. In Group II, the level reached a maximum 30 min after injection (3.7 +/- 1.5 micrograms/mL). The findings are attributed in part to the slow release of lidocaine from the biodegradable copolymer paste, which is suggested as a new drug-delivery system for local anesthetics.

Anesthesia, Epidural↗

PubMed1993

A morphine-triggered delivery system useful in the treatment of heroin addiction.

The ultimate objective of this work is to develop a device that can be triggered by morphine to release naltrexone. Two device configurations are described. In one configuration, naltrexone is dispersed in cellulose acetate phthalate microspheres which are then spray-coated with trilaurin. In the other configuration, naltrexone is dispersed in an n-octyl half ester of methyl vinyl ether and maleic anhydride copolymer and the mixture fabricated into a disk which is then coated with trilaurin. The microspheres are designed to release naltrexone abruptly while the disks are designed to release naltrexone at a constant rate over a two week period. The microspheres, or the disk along with a reversibly inactivated lipase are placed inside a semipermeable membrane that allows free passage of morphine and naltrexone but excludes the higher molecular weight components of the device. Reversible inactivation of lipase is achieved by covalent attachment of morphine and complexing with morphine antibody. Activation of the device occurs by diffusion of morphine into the device and displacing the lipase-morphine conjugate from the antibody. The activated lipase then removes the trilaurin protective coating, thus triggering naltrexone release.

Biodegradation, Environmental↗

PubMed1999

Niosomes as a novel peroral vaccine delivery system.

The feasibility to develop a peroral vaccine delivery system based on non-ionic surfactant vesicles (niosomes) was evaluated using BALB/c mice. Ovalbumin was encapsulated in various lyophilized niosome preparations consisting of sucrose esters, cholesterol and dicetyl phosphate. Two different formulations were compared in this study. The specific antibody titres within serum, saliva and intestinal washings were monitored by ELISA on days 7, 14, 21 and 28 after intragastric administration. Only encapsulation of ovalbumin into Wasag7 (70% stearate sucrose ester, 30% palmitate sucrose ester (40% mono-, 60% di/tri-ester)) niosomes resulted in a significant increase in antibody titres. Administration of ovalbumin and empty niosomes did not exert a similar effect, neither did administration of any control formulation. In contrast to ovalbumin loaded Wasag7 niosomes, application of the more hydrophilic Wasag15 (30% stearate sucrose ester, 70% palmitate sucrose ester (70% mono-, 30% di/tri-ester)) niosome preparations did not result in an increase in antibody titres.

Administration, Oral↗

PubMed2006

Micellization and reversible pH-sensitive phase transfer of the hyperbranched multiarm PEI-PBLG Copolymer.

A novel, hyperbranched, amphiphilic multiarm biodegradable polyethylenimine-poly(gamma-benzyl-L-glutamate) (PEI-PBLG) copolymer was prepared by the ring-opening polymerization of gamma-benzyl-L-glutamate-N-carboxyanhydride (BLG-NCA) with hyperbranched PEI as a macroinitiator. The copolymer could self-assemble into core-shell micelles in aqueous solution with highly hydrophobic micelle cores. As the PBLG content was increased, the size of the micelles increased and the critical micelle concentration (CMC) decreased. The surface of the micelles had a positive zeta potential. The cationic micelles were capable of complexing with plasmid DNA (pDNA), which could be released subsequently by treatment with polyanions. The PEI-PBLG copolymer formed unimolecular micelles in chloroform solution. The pH-sensitive phase-transfer behavior exhibited two critical pH points for triggering the encapsulation and release of guest molecules. Both the encapsulation and release processes were rapid and reversible. Under strong acidic or alkaline conditions, the release process became partially or completely irreversible. Thus, this copolymer system should be an attractive candidate for a gene- or drug-delivery system in aqueous media and could provide the phase-transfer carriers between water and organic media.

Biodegradation, Environmental↗

PubMed1994

Controlled release systems for proteins based on gelatin microspheres.

The preparation and characterization of biodegradable gelatin microspheres for the controlled release of peptides and proteins has been investigated. Bovine serum albumin (BSA) was chosen for incorporation into the gelatin microspheres and the spheres were characterized for the in vitro release of BSA and other properties. BSA was labelled with fluorescein isothiocyanate (FITC) for easy analysis. FITC-BSA was entrapped into the gelatin microspheres using a polymer dispersion technique developed in our earlier studies. The morphological characteristics of microspheres were analysed by optical and scanning electron microscopy (SEM). The optical and SEM photographs of FITC-BSA microspheres showed the solid spherical nature of the spheres. The entrapment efficiency of FITC-BSA was about 62%. The in vitro release pattern of FITC-BSA showed that 51% of the entrapped drug was released during the first day and the release followed approximate zero order kinetics from day 2 onwards. The total release of FITC-BSA lasted for about 8 days. SDS-PAGE analysis revealed that BSA was not degraded by this preparation of microspheres.

Biodegradation, Environmental↗

PubMed1998

Plasma protein adsorption on biodegradable microspheres consisting of poly(D,L-lactide-co-glycolide), poly(L-lactide) or ABA triblock copolymers containing poly(oxyethylene). Influence of production method and polymer composition.

Biodegradable particulate systems have been considered as parenteral drug delivery systems. The adsorption of plasma proteins on micro- and nanoparticles is determined by the surface properties and may, in turn, strongly influence the biocompatibility and biodistribution of both carriers. In the present study the influence of the polymer composition and the production method of microspheres on the in vitro plasma protein adsorption were investigated using two-dimensional electrophoresis (2-DE). Microparticles were prepared from poly(l-lactide) (l-PLA), poly(d,l-lactide-co-glycolide) (PLGA), and ABA triblock copolymers containing hydrophilic poly(oxyethylene) (B-blocks) domains connected to hydrophobic polyesters (A-blocks). Two different microencapsulation methods were employed, namely the w/o/w emulsion solvent evaporation method and the spray-drying technique. It could be demonstrated that the polymer composition and, especially, the encapsulation technique, influenced the interactions with plasma proteins significantly. For example, the percentages of several apolipoproteins in the plasma protein adsorption patterns of spray-dried PLGA- and l-PLA-particles were distinctly higher when compared to the adsorption patterns of the particles produced by the w/o/w-technique. Some adsorbed proteins were found to be characteristic or even specific for particles produced by the same method or consisting of identical polymers. Polyvinyl alcohol used as stabilizer in the w/o/w-technique may decisively influence the surface properties relevant for protein adsorption. The plasma protein adsorption on particles composed of ABA copolymers was drastically reduced when compared to microspheres made from pure polyesters. The adsorption patterns of ABA-particles were dominated by albumin. The plasma protein adsorption patterns detected on the different microspheres are likely to affect their in vivo performance as parenteral drug delivery systems.

Adsorption↗

PubMed2004

Development of biodegradable poly(propylene fumarate)/poly(lactic-co-glycolic acid) blend microspheres. I. Preparation and characterization.

We developed poly(propylene fumarate)/poly(lactic-co-glycolic acid) (PPF/PLGA) blend microspheres and investigated the effects of various processing parameters on the characteristics of these microspheres. The advantage of these blend microspheres is that the carbon-carbon double bonds along the PPF backbone could be used for their immobilization in a PPF scaffold. Microspheres containing the model drug Texas red dextran were fabricated using a double emulsion-solvent extraction technique. The effects of the following six processing parameters on the microsphere characteristics were investigated: PPF/PLGA ratio, polymer viscosity, vortex speed during emulsification, amount of internal aqueous phase, use of poly(vinyl alcohol) (PVA) in the internal aqueous phase, and PVA concentration in the external aqueous phase. Our results showed that the microsphere surface morphology was affected most by the viscosity of the polymer solution. Microspheres fabricated with a kinematic viscosity of 39 centistokes had a smooth, nonporous surface. In most microsphere formulations, the model drug was dispersed uniformly in the polymer matrix. For all fabricated formulations, the average microsphere diameter ranged between 19.0 and 76.9 microm. The external PVA concentration and vortex speed had most effect on the size distribution. Entrapment efficiencies varied from 60 to 98% and were most affected by the amount of internal aqueous phase, vortex speed, and polymer viscosity. Overall, we demonstrated the ability to fabricate PPF/PLGA blend microspheres with similar surface morphology, entrapment efficiency, and size distribution as conventional PLGA microspheres.

Biocompatible Materials↗