Biomedical subjects

I Vural

Publications and source records attributed to I Vural.

7 recordsLinked to original sources

PubMed2005

Preparation and characterization of PLGA nanospheres for the targeted delivery of NR2B-specific antisense oligonucleotides to the NMDA receptors in the brain.

Treatment of central nervous system (CNS) diseases with potentially useful pharmaceuticals is prevented by the blood-brain barrier (BBB). The BBB is a unique protective barrier in the body. It is formed by epithelial-like tight junctions, which are expressed by the brain capillary endothelial cells. Although most molecules are potentially active in the CNS, they cannot readily enter the brain because of their properties. Antisense oligonucleotides (ODNs) have a great potential as neuropharmaceuticals; however, the large size and polar nature of nucleic acid drugs prevent these molecules from bypassing the BBB and readily entering the CNS following systemic administration. One approach to improve both the pharmacokinetics and the pharmacodynamics of ODNs involves the use of sustained-release polymer formulations, such as poly(lactide-co-glycolide) (PLGA) nanoparticulate systems. In this study, nanospheres were prepared by the emulsification diffusion technique and characterized in terms of particle size, surface morphology, encapsulation efficiency, in vitro release profiles and ODN stability. The nanospheres produced were spherical with homogenous size distribution. Nanospheres were prepared with different encapsulation efficiency. Release profiles of formulations were also evaluated. The results show that formulations with different ODN content exhibited different release profiles. Moreover, the chemical integrity of ODN during the processes was conserved. These results demonstrate that a stable ODN formulation could be prepared utilizing PLGA nanospheres as a potential delivery system for the treatment of CNS diseases.

Brain↗

PubMed2004

In vitro cytotoxicity of mitoxantrone-incorporated albumin microspheres on acute promyelocytic leukaemia cells.

In the present study, the preparation and characterization of bovine serum albumin (BSA) microspheres and the evaluation of the in vitro cytotoxicity of these microspheres on acute promyelocytic leukaemia (HL-60) cells were described. Mitoxantrone (MTZ)-incorporated microspheres were evaluated for particle size, drug loading, release characteristics and surface morphology. The biological effect of MTZ released from BSA microspheres was determined on an in vitro cultured HL-60 cell line, showing that, after encapsulation, MTZ still retains cytotoxic activity. For this purpose, methyl-thiazol-tetrazolium (MTT) assay was used to evaluate the in vitro cytotoxicity of MTZ-loaded microspheres. Particle size of BSA microspheres was determined between 17.61-20.38 microm and they were smooth and spherical in shape. Encapsulation efficiency of the drug-loaded microspheres was between 22.26-60.50%. For MTZ-containing microspheres, the cell death ratios were greater than 80% for all formulations. This study demonstrate that BSA microspheres were well suited for the controlled release of MTZ and were promising for anti-cancer chemotherapy.

Animals↗

PubMed2001

Intracytoplasmic gene delivery for in vitro transfection with cytoskeleton-specific immunoliposomes.

A novel and highly efficient method of in vitro gene transfection has been developed. This method employs direct intracytoplasmic gene delivery into embryonic cardiocytes using neutral cytoskeletal-antigen specific immunoliposomes (CSIL). These immunoliposomes target cardiocytes specifically under reversible hypoxic conditions. Two independent reporter genes, pGL2 and pSV-beta-galactosidase, were used to verify CSIL-transfection (CSIL-fection). The efficiency of CSIL-fection with firefly luciferase pGL2 vector was 30+ times greater than controls consisting of hypoxic cardiocytes treated with plain liposomes (PL) or normoxic cardiocytes treated with CSIL, PL or naked DNA. CSIL-fection was also compared to cationic liposome transfection. Net cationic liposome transfection appeared to be more efficient than CSIL-fection for pGL2 vectors. However, a smaller number of viable cells was observed in the cationic liposome treated cultures than in the CSIL treated cultures. Therefore, to determine whether more cells were transfected with cationic liposomes or CSIL, pSV-beta-galactosidase vector was used. CSIL-fection with pSV-beta-galactosidase vector produced at least 40 times more transfected cells than those transfected with cationic liposomes. No transfection with pSV-beta-galactosidase vectors was obtained with IgG-liposome, PL or naked DNA treatments. Targeted enhanced efficiency of transfection by this novel method could have practical therapeutic applications in the genetic modification of cells ex vivo that could then be reimplanted into patients for gene therapy.

Animals↗

PubMed1995

Plug and seal: prevention of hypoxic cardiocyte death by sealing membrane lesions with antimyosin-liposomes.

The hallmark of cell death is the development of cell membrane lesions. Such lesions in the myocardium are usually associated with acute myocardial infarction. Minimizing myocardial necrosis by thrombolytic reperfusion therapy constitutes the only major treatment to date. We envisioned a method to seal these membrane lesions using immunoliposomes as a novel adjunctive approach. An antigen to intracellular cytoskeletal myosin in hypoxic embryonic cardiocytes is used as an anchoring site, and a specific antibody on immunoliposomes as the anchor to plug and to seal the membrane lesions. H9C2 cells were used because they are cardiocytes and are propagated in tissue culture and their viability may be assessed by various methods. Viability assessed by [3H]thymidine uptake in hypoxic cardiocyte cultures (n = 6 each) treated with antimyosin-immunoliposomes (3.26 +/- 0.483 x 10(6) c.p.m.) was similar to that of normoxic cells (3.68 +/- 0.328 x 10(6) c.p.m.), but was greater than those of untreated hypoxic cells (0.115 +/- 0.155 x 10(6) c.p.m.) or hypoxic cells treated with plain liposomes (1.140 +/- 0.577 x 10(6) c.p.m.). These results were reconfirmed by trypan blue exclusion and by fluorescent, confocal and transmission electron microscopy. They indicated that cell death in hypoxic cardiocytes can be prevented by targeted cell membrane sealing. This concept of cell salvage should be applicable in the prevention of cell death in different biological systems.

Animals↗

PubMedDate not supplied

Cyclophosphamide loaded albumin microspheres II. Release characteristics.

The purpose of this investigation was to evaluate the release characteristics of cyclophosphamide (CP) from glutaraldehyde stabilized human serum albumin microspheres, and to study the effect of the extent of cross-linking, the amount of the stabilizing agent and the size of the microspheres on the in vitro release of CP. Microspheres were prepared by emulsion polymerization method using two different volumes (0.1 and 0.7 ml) of glutaraldehyde solution (25 per cent) and two different crosslinking durations (15 min and 1 h). The resulting mean particle size of the microspheres also varied between 2.5 microns and 3.7 microns. The total CP content in microspheres was analysed from the surface drug and the entrapped drug.

Cross-Linking Reagents↗

PubMedDate not supplied

Decrease in the placental transfer of chloramphenicol when administered in albumin microspheres into rats.

Chloramphenicol is an antibiotic which can pass across the human placenta and has teratogenic effects in the foetus. When this antibiotic is entrapped in albumin microspheres and administered to pregnant rats intravenously its placental transport is significantly lowered when compared with that of free drug. Drug modifications such as entrapment are suggested as an alternative way to prevent harmful effects of drugs in case of consumption during pregnancy.

Animals↗

PubMedDate not supplied

Effect of encapsulation of chloramphenicol in albumin microspheres on its in vitro transfer across the human placenta.

The possibility of reducing drug transfer across the placenta was tested in two of our previous studies. The aim of those studies was to demonstrate an alternative method of drug application during pregnancy which we think would yield a dual benefit, i.e. protecting the foetus from the harmful effects of drugs while curing the mother. The present study was planned as a continuation of the testing of the same idea and we tried to see the effect of albumin microsphere encapsulation of chloramphenicol on its transfer across the human placenta in vitro. Microspheres containing chloramphenicol were prepared according to the method previously described. The mean per cent encapsulation of chloramphenicol in albumin microspheres was found to be 42 +/- 4.3 per cent (n = 5) and the mean size of the albumin microspheres was 3.08 +/- 0.6 mm. In vitro stability of the drug-carrying microspheres was measured by dialysing them at 37 degrees C for 24 h. Chloramphenicol was released from the microspheres gradually leaving about 50 per cent of the entrapped drug in the microspheres after 1.5 h. About 20 per cent of the chloramphenicol was retained in the microspheres at 24 h postincubation. The persistence of the antibacterial effect of the released chloramphenicol is confirmed by antibiogramme tests. In the perfusions the initial free drug concentration was kept at 100 mg/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗