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Biomedical subjects

Nesrin Hasirci

Publications and source records attributed to Nesrin Hasirci.

10 recordsLinked to original sources
PubMed2005

Desferrioxamine release from gelatin-based systems.

The conventional treatment with regular red-blood-cell transfusions and simultaneous chelation of excess iron with DFO (desferrioxamine) improves quality of life of thalassaemic patients while increasing their rate of survival considerably. Although DFO is the main iron- chelating drug currently utilized, it has various drawbacks, including high cost, poor oral effectiveness, toxicity and short plasma half-life. It has to be administered by slow, subcutaneous infusion during blood transfusion for 8-12 h at night, 5-7 nights a week, and this leads to a very poor patient compliance. In order to avoid frequent and uncomfortable infusions of DFO, application of controlled-release systems might be alternative routes in the supportive treatment of thalassaemia. In the present study, GMs (gelatin microspheres) and GFs (gelatin films) were prepared by coacervation and casting methods respectively to develop controlled DFO-release systems. Cross-linking by glutaraldehyde and carbodi-imide were performed to increase the stability of gelatin matrices. Microspheres and films prepared without the addition of cross-linker degraded completely in 4 h. On the other hand, addition of cross-linker extended this time from hours to weeks depending on the added amount. Therefore the amount of DFO released from microspheres in 7 days was found to be in the range 12-82%, whereas the amount permeated through the films in 5.0 h was found to be in the range 34-67%. GFs were elastic and demonstrated good mechanical properties. Films achieved 0.14-0.69 MPa tensile strength, with 0.12-1.29 MPa elastic modulus and 26.49-109.38% strain values at break point. These studies showed that gelatin-based controlled-release systems could be improved and could be good candidates for the production of long-term DFO-carrying systems.

Biocompatible Materials↗
PubMed2005

Preparation and characterization of a biodegradable drug targeting system for anticancer drug delivery: microsphere-antibody conjugate.

Targeted delivery of anticancer drugs is one of the most actively pursued goals in anticancer chemotherapy. A major disadvantage of anticancer drugs is their lack of selectivity for tumour tissue, which causes severe side effects and results in low cure rates. Any strategy by which a cytotoxic drug is targeted to the tumour, thus increasing the therapeutic index of the drug, is a way of improving cancer chemotherapy and minimizing systematic toxicity. This study covers the preparation of the gelatin microsphere (GM)-anti-bovine serum albumin (anti-BSA) conjugate for the development of a drug targeting approach for anticancer drug delivery. Microspheres of 5% (w/v) gelatin content were prepared by crosslinking with glutaraldehyde (GTA) at 0.05 and 0.50% (v/v) concentration. Microspheres were in the size range of 71-141?microm. The suitability of these microspheres as drug carriers for anticancer drug delivery was investigated in vitro by studying the release profiles of loaded methotrexate (MTX) and 5-fluorouracil (5-FU) and the cytotoxicities on cancer cell lines. The in vitro MTX release profiles (approximately 22-46% released in 24 h depending on the amount of GTA used) were much slower compared to 5-FU (approximately 42-91% released in 24 h). Both drugs demonstrated an initial fast release, which was followed by gradual, sustained drug release. The MTT cytotoxicity test results of GMs loaded with 5-FU and MTX showed approximately 54-70% and approximately 52-67% cytotoxicities in 4 days. In general, incorporation of MTX and 5-FU in microspheres enhanced the cytotoxic effect in a more prolonged manner compared to the free drugs. Gelatin micospheres were chemically conjugated to anti-BSA and the antigen-antibody activities were studied by immunofluorescence. Results indicated approximately 80% binding with conjugated anti-BSA and BSA-FITC. Based on their low cytotoxicity and the high antigen binding efficiencies, anti-BSA conjugated gelatin microspheres could be suitable targeted drug carrier systems for selective and long-term delivery of anticancer drugs to a specific body compartment (i.e. bladder cancer).

Antibodies↗
PubMed2004

Prolonged cytotoxic effect of colchicine released from biodegradable microspheres.

One the main problems of cancer chemotherapy is the unwanted damage to normal cells caused by the high toxicities of anticancer drugs. Any system of controlled drug delivery that would reduce the total amount of drug required, and thus reduce the side effects, would potentially help to improve chemotherapy. In this respect, biodegradable gelatin microspheres were prepared by water/oil emulsion polymerization and by crosslinking with glutaraldehyde (GTA) as the drug-carrier system. Microspheres were loaded with colchicine, a model antimitotic drug, which was frequently used as an antimitotic agent in cancer research involving cell cultures. Microsphere sizes, swelling and degradation properties, drug-release kinetics, and cytotoxities were studied. Swelling characteristics of microspheres changed upon changing GTA concentration. A decrease in swelling values was recorded as GTA crosslink density was increased. In vitro drug release in PBS (0.01M, pH 7.4) showed rapid colchicine release up to approximately 83% (at t = 92 h) for microspheres with low GTA (0.05% v/v), whereas a slower release profile (only approximately 39%) was obtained for microspheres with high GTA (0.50% v/v) content, for the same period. Cytotoxicity tests with MCF-7, HeLa and H-82 cancer cell lines showed that free colchicine was very toxic, showing an approximately 100% lethal effect in both HeLa and H-82 cell lines and more than 50% decrease in viability in MCF-7 cells in 4 days. Indeed, entrapped colchicine indicated similar initial high toxic effect on cell viability in MCF-7 cell line and this effect became more dominant as colchicine continued to be released from microspheres in the same period. In conclusion, the control of the release rate of colchicine from gelatin microspheres was achieved under in vitro conditions by gelatin through the alteration of crosslinking conditions. Indeed, the results suggested the potential application of gelatin microspheres crosslinked with GTA as a sustained drug-delivery system for anticancer drugs for local chemotherapy administrations.

Biocompatible Materials↗
PubMed2004

Sustained local application of low-dose epidermal growth factor on steroid-inhibited colonic wound healing.

BACKGROUND/PURPOSE: The effects of locally administered low-dose epidermal growth factor in a steroid-inhibited wound healing were investigated in a rat model. METHODS: Long-acting release of epidermal growth factor was enabled using microspheres embedded in gelatin sponge. Study groups consisted of 60 rats with 10 in each: colonic anastomosis only (C), plus pure gelatin sponge (CG), plus epidermal growth factor loaded sponge (CE), colonic anastomosis and steroid (S), plus gelatine sponge (SG), and plus epidermal growth factor-loaded gelatine sponge (SE) groups. Bursting pressure and wound hydroxy-proline content were measured. Bursting sites were recorded. Collagen deposits, inflammation, and foreign body reactions were evaluated. RESULTS: Bursting pressure and hydroxy-proline contents were found lowest in the S and highest in the CE groups (P <.01). There was almost no difference between C and SE groups. Bursts were encountered in peri-anastomotic normal colon sites in the nonsteroid-treated C, CG, and CE groups. They were noted overwhelmingly at the anastomosis in steroid-inhibited S, SG, and SE groups. Histopathology results showed a standstill at the inflammatory phase of healing in S and SG groups. The best healing was observed in the CE group. Degree of collagen accumulation was well correlated with bursting pressure and hydroxy-proline content data with a negligible foreign body reaction to gelatine sponge. CONCLUSIONS: Continuous local epidermal growth factor administration by microspheres in gelatin increases wound collagen and further enhances healing in colonic anastomoses even with steroid inhibition.

Anastomosis, Surgical↗
PubMed2004

The effects of local and sustained release of fibroblast growth factor on testicular blood flow and morphology in spermatic artery--and vein-ligated rats.

BACKGROUND/PURPOSE: This study was carried out to evaluate the effects of local and sustained release of fibroblast growth factor (FGF) on testicular blood flow and morphology in spermatic artery--and vein-ligated rats. METHODS: Forty male Wistar albino rats weighting 300 +/- 20 g were allocated randomly into 5 groups consisting of 8 in each as follows: G-S (sham); G-C (control); and G-T0.85, G-T1.70, G-T2.55. After the ligation of the left spermatic artery and vein, 1 cm2 of unloaded and 0.85 microg, 1.70 microg, and 2.55 microg of FGF-loaded gelatin films were sutured on the left epididymis in G-C, G-T0.85, G-T1.70, and G-T2.55, respectively. After 30 days, bilateral capsular (CBF) and intratesticular (IBF) blood flows were evaluated by colored Doppler ultrasonography (CDUS) and testicular blood flow (TBF) by 133Xe clearance technique. Tunica albuginea and intertubular tissues were studied for the increase of peritesticular and intratesticular vessels. Mean intertubular vascular structure counts, seminiferous tubular diameters, testicular biopsy scores, and Leyding cell scores of each group were recorded and compared. RESULTS: CBF was present in all animals of G-S, G-T0.85, G-T1.70, and G-T2.55 groups in CDUS, and it was detected in 62% of the G-C rats (P < .05). However, IBF was present in only 25% of the G-C rats, and this percentage was increased from 50% up to 87.5% for treatment groups, and 100% for G-S rats, respectively. 133Xe clearance showed that TBF was significantly decreased in G-C compared with G-S (P < .05). In G-T2.55, TBF was significantly increased, but still could not reach the level of G-S. Although mean testicular weights were significantly decreased for controls (G-C), G-T0.85, and G-T1.70, almost no difference was observed between G-T2.55 and G-S. Although a slight increase in the vascular structures of tunica albuginea was present in G-C rats, a significant increase was observed in treatment groups. The mean number of intertubular vascular structures was significantly increased in treatment groups when compared with G-S and G-C (P < .05). Mean seminiferous tubular diameters and Leydig cell scores were decreased in G-C but significantly increased in treatment groups (P < .05). Mean testicular biopsy scores were increased in treatment groups compared with G-C but could not reach to sham levels. CONCLUSIONS: Ligation of the spermatic artery and vein has detrimental effects on the ipsilateral testicular blood flow and morphology. These effects may be reversed by local application of FGF.

Animals↗
PubMed2002

Oxygen plasma modification of polyurethane membranes.

Polyurethane membranes were prepared under nitrogen atmosphere by using various proportions of toluene diisocyanates (TDI) and polypropylene-ethylene glycol (P) with addition of no other ingredients such as catalysts, initiator or solvent in order to achieve medical purity. Effects of composition on mechanical properties were examined. In general, modulus and UTS values demonstrated an increase and PSBR demonstrated a decrease as the TDI/Polyol ratio of the polymer increased. Elastic modulus, ultimate tensile strength (UTS) and per cent strain before rupture (PSBR) values were found to be in the range of 1.4-5.4 MPa, 0.9-1.9 MPa, and 60.4-99.7%, respectively. Surfaces of the membranes were modified by oxygen plasma applying glow-discharge technique and the effect of applied plasma power (10 W or 100 W, 15 min) on surface hydrophilicity and on the attachment of Vero cells were studied. Water contact angle values of the plasma modified surfaces varied between 67 degrees and 46 degrees, demonstrating a decrease as the applied plasma power was increased. The unmodified material had 42-45 cells attached per cm(2). It was observed that as the applied power increased the number of attached cells first increased (60-70 cells/cm(2) at 10 W) and then decreased (27-40 cells/cm(2) at 100 W). These demonstrated that surface properties of polyurethanes can be modified by plasma-glow discharge technique to achieve the optimum levels of cell attachment.

Journal Article↗
PubMed2002

Cytotoxicity evaluation of gelatin sponges prepared with different cross-linking agents.

Gelatin is a natural polymer used in pharmaceutical and medical applications, especially in the production of biocompatible and biodegradable wound dressings and drug delivery systems. Gelatin granules hydrate, swell and solubilize in water, and rapidly degrade in vivo. The durability of these materials could, however, be prolonged by cross-linking by aldehydes, carbodiimides, and aldose sugars, but the biocompatibility of collagenous biomaterials is profoundly influenced by the nature and extent of cross-linking. In this study, gelatin sponges were prepared by using various cross-linkers such as glutaraldehyde (GA), 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDAC), and D-fructose. The effects of the type and the amount of cross-linker on thermal and mechanical properties, stability, and cytotoxicity were investigated. The mechanical analysis data showed that an increase in the amount of GA in the sponge structures caused a slight increase in the modulus of elasticity but had almost no effect on the tensile strength. Increase in the EDAC concentration produced a maximum in the modulus of elasticity and tensile strength values. The stability of the sponges and the time required for complete degradation in aqueous media increased in parallel with the cross-linker content. In vitro studies carried out with fibroblast cells demonstrated a higher cell viability for the samples cross-linked with low concentrations of GA than for those cross-linked with EDAC.

Biocompatible Materials↗
PubMed2002

Gelatin microspheres and sponges for delivery of macromolecules.

Gelatin microspheres and gelatin sponges were prepared by coacervation and freeze drying techniques, respectively. Both systems were crosslinked with glutaraldehyde. The mean diameter of the microspheres were in the range of 40-80 microm and the mean pore size of the sponges was 130-220 microm depending on the preparation conditions. Bovine serum albumin (BSA) was added into the preparation solutions and entrapped in the microspheres and sponges. BSA addition to sponges was also achieved by addition of BSA-containing microspheres into the sponges. The release kinetics of BSA from the prepared systems were examined. Studies demonstrated that release is dependent on the amount of BSA present in the system and crosslinking densities of microspheres. It was concluded that gelatin microspheres and gelatin sponges are promising carrier matrices for macromolecules.

Drug Carriers↗