Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chitosan, a polysaccharide, having structural characteristics similar to glycosaminoglycans, seems to be nontoxic and bioabsorbable. This study highlights the use of chitosan matrix for controlled drug delivery systems. The steroid drugs, namely testosterone, progesterone and beta-oestradiol were mixed with chitosan and the films were prepared by evaporation technique. The in vitro release profile of these steroids from the film matrix was monitored, as a function of time, in phosphate buffered saline (PBS, pH 7.4) at 37 degree C using a U-V-spectrophotometer. The degradation, of these chitosan and drug loaded chitosan films, was also investigated by weight loss and tensile strength studies. The steroid release from chitosan films was compared with the release of these drugs from their microbeads. It appears, the films and the microbeads stayed intact during the dissolution study of 90 days and the possibility of using these systems in contraceptive applications and novel drug delivery systems are discussed.
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PMID:Biodegradable chitosan matrix for the controlled release of steroids. 181 Apr 8

Endothelial cell growth factor (ECGF) stimulates vascularization, however its relatively short half-life requires this angiogenic factor to be frequently administrated by non-specific and uncontrolled methods. This work describes the use of biocompatible chitosan, a polysaccharide having structural similarity to glycosaminoglycans, -albumin microspheres, as well as its fiber form, as a potential delivery system for the controlled and localized release of ECGF. Chitosan-albumin microspheres (400-600 microns) and fibers, formed in 0.5 M sodium hydroxide-methanol solution were incubated with ECGF. In vitro release was performed in PBS at 37 degrees C, under constant stirring. In vivo experiments were realized by implanting ECGF loaded matrices subcutaneously into rat groin fascia. After an initial ECGF burst of 1.32-1.62 mg (22-27%) within the first 2 hours, a daily release of 120-420 micrograms (2-7%) during the first, and 60-240 micrograms (1-4%) during the second week was observed from M(r) 70.000, 750.000, and 2,000.000 chitosan containing microspheres of 6 mg/ml loading. ECGF release rate of < 30 micrograms (0.5%)/day was maintained during the third week of experiments. By the increase in ECGF loading (12 mg/ml polymer), while the amount of release increased, percent release decreased. Chitosan-albumin fibers gave a ECGF release rate nearly similar to microspheres, and in vivo studies demonstrated a high degree of neovascularization for both types of implants, starting from 7 day-post implantation. Control animals that received ECGF injection did not show any significant neovascularization, after same period of time.
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PMID:Controlled release of endothelial cell growth factor from chitosan-albumin microspheres for localized angiogenesis: in vitro and in vivo studies. 877 42

Chitosan nanoparticles (CS NP) with various formations were produced based on ionic gelation process of tripolyphosphate (TPP) and chitosan. They were examined with diameter 20-200 nm and spherical shape using TEM. FTIR confirmed tripolyphosphoric groups of TPP linked with ammonium groups of chitosan in the nanoparticles. Factors affecting delivery properties of bovine serum albumin (BSA) as model protein have been tested, they included molecular weight (Mw) and deacetylation degree (DD) of chitosan, the concentration of chitosan and initial BSA, and the presence of polyethylene glycol (PEG) in encapsulation medium. Increasing Mws of chitosan from 10 to 210 kDa, BSA encapsulation efficiency was enhanced about two times, BSA total release in PBS (phosphate buffer saline) pH 7.4 in 8 days was reduced from 73.9 to 17.6%. Increasing DD from 75.5 to 92% promoted slightly the encapsulation efficiency and decelerated the release rate. The encapsulation efficiency was highly decreased by increase of initial BSA and chitosan concentration; higher loading capacity of BSA speeded the BSA release from the nanoparticles. Adding PEG hindered the BSA encapsulation and accelerated the release rate.
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PMID:Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. 1248 Feb 87

To prevent a rapid drug release from alginate microspheres in simulated intestinal media, alginate microspheres were coated or blended with polymers. Three polymers were selected and evaluated such as HPMC, Eudragit RS 30D and chitosan, as both coating materials and additive polymers for controlling the drug release. This study focused on the release characteristics of polymer-coated and blended alginate microspheres, varying the type of polymer and its concentration. The alginate microspheres were prepared by dropping the mixture of drug and sodium alginate into CaCl(2) solution using a spray-gun. Polymer-coated microspheres were prepared by adding alginate microspheres into polymer solution with mild stirring. Polymer-blended microspheres were prepared by dropping the mixture of drug, sodium alginate and additive polymer with plasticizer into CaCl(2) solution. In vitro release test was carried out to investigate the release profiles in 500 ml of phosphate buffered saline (PBS, pH 7.4). As the amount of polymer in sodium alginate or coating solution increase, the drug release generally decreased. HPMC-blended microspheres swelled but withstood the disintegration, showing an ideal linear release profiles. Chitosan-coated microspheres showed smooth and round surface and extended the release of drug. In comparison with chitosan-coated microspheres, HPMC-blended alginate microspheres can be easily made and used for controlled drug delivery systems due to convenient process and controlled drug release.
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PMID:Preparation and release characteristics of polymer-coated and blended alginate microspheres. 1255 73

Chitin and chitosan derivatives are used as excipients and drug carriers in the pharmaceutical field. Their derivatization contributed to expansion of application and decrease toxicity. Chitosan is used as an excipient in oral dosage form. Chitosan tablet can exhibit a sustained drug release compared to commercial products. Films prepared using chitin or chitosan have been developed as wound dressings, oral mucoadhesive and water-resisting adhesive by virtue of their release characteristics and adhesion. Intratumoral administration of gadopentetic acid-chitosan complex nanoparticles (approximately 430 nm in diameter) has been more effective for gadolinium neutron-capture therapy compared with a group treated with the solution. Compared to intragastrical feeding with diphtheria toxoid (DT) in PBS, a strong enhancement of the systemic (IgG) and local (IgA) immune responses against DT has been observed in mice fed with DT loaded chitosan microparticles (approximately 4.7 microm in size). When DNA-loaded chitosan microspheres (1.15 - 1.28 microm) were intramuscularly administrated into mice, high beta-galactosidase and luciferase productions were obtained even after a long post-transfection period (12 weeks). N-Succinyl-chitosan (Suc-Chi) has been studied for cancer chemotherapy as a drug carrier and the conjugates of mitomycin C with Suc-Chi exhibited good antitumor activities against various tumors. Furthermore, trimethyl-chitosan and monocarboxymethyl-chitosan has been shown to be effective as intestinal absorption enhancers due to their physiological properties. Chitosan-thioglycolic acid conjugates has been found to be a promising candidate as scaffold material in tissue engineering due to their physicochemical properties. This review summarizes the application of chitin and chitosan derivatives for hospital preparations and drug carriers.
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PMID:Application of chitin and chitosan derivatives in the pharmaceutical field. 1452 20

A possible alternative for immunosuppression is a microencapsulation technique using hydrogels, which have been utilized for cell immobilization and drug delivery systems. Angiogenesis is crucial for delivery of the metabolic products to the host tissues as well as to supply oxygen and nutrients to cells. The local delivery of angiogenic growth factors, such as VEGF and basic FGF, has been recently studied to enhance angiogenesis on peripheral tissue of graft. In this study, we evaluated sustained VEGF release with a model using hydrogels coated with chitosan and heparin in vitro. We fabricated calcium alginate gels and chitosan-coated calcium alginate gels. Heparinized chitosan-coated calcium-induced alginate hydrogel beads were prepared by soaking chitosan-coated calcium alginate gels in heparin solution. We compared the stability and VEGF release manner between three kinds of hydrogels. To compare the stability, 5 mL of each hydrogel was incubated with 20 mL PBS under the rotational culture. Compression forces were measured using a rheometer. The amount of VEGF released from the gels was measured by ELISA. The heparin-coated chitosan alginate hydrogels showed the highest surface stability among the three hydrogels. VEGF from the heparinized gel was released in sustained manner up to 10 days in vitro. Chitosan-coated alginate gels released 90% of loaded VEGF within 5 days. These results suggest that local delivery of VEGF using a heparinized hydrogel may provide a long-term supply of angiogenic growth factor that might induce new vessel formation in vivo.
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PMID:Sustained release of vascular endothelial growth factor from calcium-induced alginate hydrogels reinforced by heparin and chitosan. 1556 Dec 82

The potential of chitosan as a polycationic gene carrier for oral administration has been explored since 1990s. Chitosan has been shown to effectively bind DNA in saline or acetic acid solution and protect DNA from nuclease degradation. In this study, pDNA (plasmid DNA) was encapsulated in chitosan microparticles. Chitosan-DNA microparticles were prepared using a complex coacervation process and stability of plasmid DNA was investigated in this complex. The chitosan-DNA microparticles could protect the encapsulated plasmid DNA from nuclease degradation. Release of pDNA from microparticles was studied in simulated gastric, simulated intestinal medium and acidic PBS (phosphate buffer saline) (pH 4.5) buffer at 37 degrees C, and released pDNA was assayed spectrophotometrically. In vitro release of pDNA from chitosan microparticles was dependent on pH, as the pH of the release medium increased release profile decreased. In in vivo-animal studies blue color was observed with X-gal (4-chloro-5-bromo-3-indolyl-beta-galactosidase) staining of histological stomach and small intestine sections after oral administration of pDNA-chitosan microparticles as an indicator of exogeneous gene expression.
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PMID:Chitosan microparticles containing plasmid DNA as potential oral gene delivery system. 1625 20

In order to develop a mucosal delivery system based on biocompatible polymers, a new methodology for production of protein-loaded microparticles is developed. Chitosan anionic precipitation/coacervation is accomplished by the addition of sodium deoxycholate (DCA). These microparticles were prepared under mild conditions, where bovine serum albumin (BSA) and DCA were simply dipped into a chitosan solution under stirring. Platelet-like and/or spherical microparticles, having high protein loading efficiency and relatively low protein external exposure, are obtained. To achieve a better compaction of the microparticle matrix, block copolymers and other non-ionic surfactants are added to the formulation. BCA analysis and fluorescence quenching were used to assess the degree of protein exposure. BSA release profiles for chitosan-DCA formulations in PBS pH 7.4 and HCl 0.1 N revealed, in most cases, an initial burst release, but more than 55% of the BSA remains protected inside the microparticles. It is also observed that in acidic environment (HCl 0.1 N) the protein is better shielded from the environment. Some of the formulations show good properties for mucosal protein delivery, and one of those here developed is now being tested in vivo, for mucosal administration of an adenovirus vaccine.
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PMID:Incorporation of a model protein into chitosan-bile salt microparticles. 1648 Aug 40

Chitosan is a well sought-after polysaccharide in biomedical applications and has been blended with various macromolecules to mitigate undesirable properties. However, the effects of blending on the unique antibacterial activity of chitosan as well as changes in fatigue and degradation properties are not well understood. The aim of this work was to evaluate the anti-bacterial properties and changes in physicochemical properties of chitosan upon blending with synthetic polyester poly(epsilon-caprolactone) (PCL). Chitosan and PCL were homogeneously dissolved in varying mass ratios in a unique 77% acetic acid in water mixture and processed into uniform membranes. When subjected to uniaxial cyclical loading in wet conditions, these membranes sustained 10 cycles of predetermined loads up to 1 MPa without break. Chitosan was anti-adhesive to Gram-positive Streptococcus mutans and Gram-negative Actinobacillus actinomycetemcomitans bacteria. Presence of PCL compromised the antibacterial property of chitosan. Four-week degradation studies in PBS/lysozyme at 37 degrees C showed initial weight loss due to chitosan after which no significant changes were observed. Molecular interactions between chitosan and PCL were investigated using Fourier transform infrared spectroscopy (FTIR) which showed no chemical bond formations in the prepared blends. Investigation by wide-angle X-ray diffraction (WAXD) indicated that the crystal structure of individual polymers was unchanged in the blends. Dynamic mechanical and thermal analysis (DMTA) indicated that the crystallinity of PCL was suppressed and its storage modulus increased with the addition of chitosan. Analysis of surface topography by atomic force microscopy (AFM) showed a significant increase in roughness of all blends relative to chitosan. Observed differences in biological and anti-bacterial properties of blends could be primarily attributed to surface topographical changes.
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PMID:Blending chitosan with polycaprolactone: effects on physicochemical and antibacterial properties. 1660 30

Systemic and local immune response against Chitosan encapsulated tetanus toxoid (CS-TT) microparticles is studied, prepared by ionic cross-linking using Sodium Tripolyphosphate (STPP). Final formulation was evaluated in terms of release of TT in 0.1 N HCl and PBS (pH 7.4), sedimentation profile and stability. CS-TT microparticles, TT in PBS and plain CS microparticles were orally administered to mice and TT (adsorbed) was administered through intramuscular route. Sera were analyzed for anti-TT IgG and intestinal lavage, faeces, intestinal washings for anti-TT IgA levels using an ELISA. Entrapment efficiency of about 100% was obtained. A dose dependent immune response was observed in mice vaccinated with Chitosan-TT microparticles. A strong enhancement of the systemic and local immune response against TT were found when compared with oral feeding of TT in PBS. The study shows the efficacy of chitosan microparticle suspension system, containing a high molecular protein (TT), in inducing the IgA in intestine and IgG in systemic circulation. This demonstrates that chitosan microparticles can prove to be a promising oral vaccine delivery system for mucosal and systemic immunity.
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PMID:Chitosan microparticles as oral delivery system for tetanus toxoid. 1785 63


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