Tumour-specific hybrid nanoparticles in therapy of breast cancer.

In this study, salicylic acid (SA) dopped into poly(3-hydroxybutyrate) (PHB) and prepared nanoparticles (NPs) to increase encapsulation efficiency, anti-cancer activity of caffeic acid (Caff), and folic acid (FA) for breast cancer treatment. NPs were prepared by solvent evaporation method and characterised by FTIR, DSC, SEM, and entrapment-loading efficiencies. The mean diameter, polydispersity index (PDI), and zeta potential (ZP) were evaluated by dynamic light scattering (DLS). In vitro release and stability studies were done via eppendorf method. The cytotoxicity, cell dead and internalisation of NPs were shown by MTT, fluorescein and confocal microscopy. The diameter and ZP of NPs were 172 ± 7 nm and -29 ± 0.38 mV. The entrapment efficiencies of 5 and 10 Caff NPs were 79 ± 0.23% and 70 ± 0.42%. NPs showed good stability within 30 d and sustained release over 25 d. FA-5Caff NPs showed 37 ± 0.3% viability on MCF-7. FA-Caff NPs were identified as promising carrier system for breast cancer therapy.

Comparison of the topical haemostatic efficacy of nano-micro particles of clinoptilolite and kaolin in a rat model of haemorrhagic injury.

PURPOSE: This study was designed to investigate if the potential haemostatic efficacy of gauze-impregnated clinoptilolite created with nano-technology is as strong as the widely used kaolin to control pulsatile arterial bleeding due to major vascular injury. METHODS: 42 rats were separated into three groups of kaolin, clinoptilolite and control groups. The femoral artery was isolated and active arterial haemorrhage was performed. After 30 s of free arterial haemorrhage, compression was applied with a standard 100 g scale and haemostasis was assessed at the 1st, 3rd and 5th minutes. All groups were observed throughout 60 min for survival without any fluid resuscitation and the mean arterial pressure, pulse, body/surface temperature and arterial blood gas values were measured. RESULTS: In the control group, haemostasis did not develop in any of the 12 rats and the survival rate was 5/12 (41.66 %). In the kaolin group, haemostasis developed in seven rats and of these, bleeding reoccurred in four. The survival rate was 10/13 (76.92 %). In the clinoptilolite group, haemostasis developed in eight rats and bleeding recurred in only one. The survival rate was 100 %. In terms of survival, the clinoptilolite and kaolin groups showed superiority to the control group (p = 0.002, p = 0.082). In the evaluation of recurrent haemorrhaging in the rats with haemostasis, clinoptilolite was observed to provide better coagulation than kaolin. CONCLUSION: A statistically significant difference was determined in clinoptilolite and kaolin group, when they are separately compared with the control group in respect of the effect on MAP, HCO3 (-), lactate, base excess, haemostasis duration and survival rates. The effect of clinoptilolite on haemostasis and survival time was observed to be at least as good as that of kaolin; therefore, clinoptilolite can be used as an active ingredient in a topical haemostat.

Chitosan-coated alginate membranes for cultivation of limbal epithelial cells to use in the restoration of damaged corneal surfaces.

Some chemicals or thermal burns may result in abnormal reepithelialization by conjunctival epithelial cells and it causes different types of damage on the cornea surface. When reepithelialization does not occur, chronic inflammation and neovascularization develop, often leading to stroma scarring and/or ulceration. The aim of this study is to restore the human corneal surface with autologous corneal epithelial sheets generated by serial cultivation of the limbal epithelial cells over the different compositions of composite membranes. The composite membranes were prepared by coating the alginate membrane with chitosan. In this method, alginate membrane was prepared by precipitation of the sodium alginate solution in calcium chloride solution. Alginate membranes were washed, dried and immersed into the chitosan solutions to prepare composite membranes. The composite membranes were characterized based on their morphology, hydrophilicity, swellability, and chemical structure. In the last part of the study, composite membranes were used as base matrices for limbal epithelial cell cultivation. The cell cultivation on polymeric membranes was investigated as the in vitro studies. In these studies cell attachment, spreading and growth on polymeric membranes were evaluated.

Preparation and characterization of Mitomycin-C loaded chitosan-coated alginate microspheres for chemoembolization.

Mitomycin-C loaded and chitosan-coated alginate microspheres were prepared for use in chemoembolization studies. In this respect, first alginate microspheres were prepared by using a spraying method using an extrusion device with a small orifice and following suspension cross-linking in an oil phase. Chitosan-coating onto the alginate microspheres was achieved by polyionic complex formation between alginate and chitosan. CaCl(2) was used as a cross-linker for alginate microspheres. The obtained chitosan-coated alginate microspheres were spherical shaped and approximately 100-400 microm average size. The microspheres were evaluated based on their swellability and the swelling ratio was changed between 50-280%. CaCl(2) concentration, stirring rate, chitosan molecular weight, chitosan concentration and time for coating with chitosan were selected as the effective parameters on microsphere size and swelling ratio. Equilibrium swellings were achieved in approximately 30 min. On the other hand, chitosan molecular weight, chitosan concentration and time for coating with chitosan were found as the most effective parameters on both drug loading ratio and release studies. Maximum drug loading ratio of 65% was achieved with high molecular weight (HMW) chitosan, highest chitosan concentration (i.e. 1.0% v/v) and shortest time for coating with chitosan (i.e. 1 h) values.

5-fluorouracil loaded chitosan microspheres for chemoembolization.

In this study, chitosan microspheres were prepared by a suspension cross-linking technique. A petroleum ether/mineral oil mixture was used as the suspension medium which includes an emulsifier, e.g. Tween-80. Glutaraldehyde was used as the cross-linker. 5-Fluorouracil was incorporated in the matrix for the possible use of the microspheres in chemoembolization. The size and size distribution of the chitosan microspheres varied in the size range of 100-200 microns, by changing the emulsifier concentration, stirring rate, chitosan/solvent ratio and drug/chitosan solution ratio. In summary, the size and size distribution of the microspheres decreased when the emulsifier concentration and stirring rate were increased. Smaller microspheres with narrower size distributions were obtained when the chitosan/solvent ratio and drug/chitosan ratio were lower. It was possible to load the chitosan microspheres with 5-FU to a concentration of 10.4 mg 5-FU/g chitosan. Around 60% of the loaded drug was released within the first 24 h, then the release rate became much slower.

Rifampicin carrying polyhydroxybutyrate microspheres as a potential chemoembolization agent.

In this study, we attempted to prepare microspheres from a microbial biodegradable polyester, i.e. polyhydroxybutyrate (PHB) as a potential chemoembolization agent. The drug loaded PHB microspheres were prepared by a solvent evaporation technique, in which methylene chloride, distilled water, and polyvinyl alcohol were utilized as the solvent, dispersion medium, and emulsifier, respectively. Microspheres were obtained within a size range of 5-100 microns by changing the initial polymer/solvent ratio, emulsifier concentration, stirring rate, and initial drug concentration. It was possible to obtain PHB with very narrow size distributions by applying gravity field-flow fractionation technique. Very high drug loadings of up to 407.6 mg rifampicin/g PHB were achieved. Drug release rates were very rapid. Almost 90% of the drug loaded was released in about 24 h. Both the size and drug content of PHB microspheres were found to be effective in controlling the drug release from these microspheres.

Rifampicin carrying poly (D,L-lactide)/poly(ethylene glycol) microspheres: loading and release.

The aim of this study is to prepare rifampicin-loaded poly (D,L-lactide)/poly(ethylene golycol) (PDLLA/ PEG) copolymer microspheres as an injectable drug delivery system. PDLLA homopolymers with three different molecular weights (9,760, 14,540, and 23,050 daltons) were synthesized and then transesterified with PEG (with a molecular weight of approximately 3,300-4,000 daltons). By changing the ratio of PEG to PDLLA, block copolymers with different chain structures were synthesized. PDLLA and PDLLA/PEG microspheres in the size range of 2-10 microns were prepared by a modified solvent evaporation technique with the use of methylene chloride as the solvent and methyl cellulose as the emulsifier within the aqueous dispersion medium. Rifampicin was loaded within the microspheres during particle formation. Effects of the solvent/polymer and drug/polymer ratios, PDLLA molecular weight, and PEG content on drug loading and release were investigated. High drug loadings up to 100 mg rifampicin/g polymer were achieved. Both size and drug loadings were decreased by an increase in the solvent/polymer ratio and PEG content and by a decrease in the drug/polymer ratio and PDLLA molecular weight. High release rates were observed in the first 5 days after which constant and slow release rates were noted. Drug release was decreased by a decrease in the solvent/polymer ratio and PEG content and by an increase in the drug/polymer ratio and PDLLA molecular weight.

A potential soft tissue filling material: chloramphenicol loaded poly(D,L-lactide) sponges.

Poly(D,L-lactide) (PDLLA) homopolymers were produced by the ring opening polymerization of a D,L-lactide dimer by using stannous chloride as the catalyst. Chloramphenicol loaded PDLLA sponges were pre- pared by a solvent evaporation procedure by using the PDLLA homopolymers with three different molecular weights (i.e., 11,000, 20,000 and 35,000 daltons). Chloramphenicol loading was changed by using three different solvents (i.e., acetone, ethyl acetate, and acetonitrile) and by changing the initial polymer concentration and its molecular weight and the initial concentration of the drug. Higher degradation rates of the chloramphenicol loaded PDLLA sponges in alkaline pH 9.0 and at 37 degrees C were observed. Chloramphenicol release rates were also high at these conditions. It was concluded that chloramphenicol release was both degradation and diffusion controlled.

Rifampicin-carrying poly(D,L-lactide) microspheres: loading and release.

Rifampicin-loaded poly(D,L-lactide) (PDLLA) microspheres in the size range of 0.8-8.0 microns were prepared by a modified solvent evaporation method. Rifampicin loading was changed by using different types of solvents (i.e. methylene chloride, chloroform, and carbon tetrachloride) with different solvent/polymer ratios and different emulsifiers (i.e. methyl cellulose, gelatin, and Tween-20), and by changing the initial drug/polymer ratio. These rifampicin-loaded PDLLA microspheres degraded much faster in the medium at basic pH (9.8) and at high temperatures (55 degrees C). Rifampicin release was also high under these conditions. It was concluded that rifampicin release was both degradation- and diffusion-controlled.

Novel PDLLA/PEG copolymer micelles as drug carriers.

In this study we attempted to develop a novel drug delivery system in the form of polymeric micelles. In order to obtain polymer chains with micelle forming abilities, we have proposed to produce copolymers by transesterification of poly(DL-lactic acid)(PDLLA)(as the hydrophobic segment) and polyethylene glycol (PEG) (as the hydrophilic segment). We first produced homopolymers of PDLLA with low molecular weights by condensation polymerization of DL-lactic acid. The PDLLA homopolymer with an average molecular weight of 1866 +/- 100 was then transesterified with PEG with a molecular weight range of 3300-4000. By changing the ratio of PEG to PDLLA, we were able to produce copolymers with different chain structures, and therefore, with different micelle forming abilities. FTIR, 1H-NMR, DSC, and GPC studies were performed to describe the structures of these PDLLA/PEG copolymers. Micelles of these copolymers were characterized by light scattering. We selected a model drug, i.e. adriamycin, and obtained the drug loadings to the PDLLA/PEG copolymer micelles. The maximum drug loading was about 12 mg g-1. We found that these micelles were degraded in phosphate buffer (pH 7.4 and temperature 37 degrees C) in about 5-6 weeks. We also investigated the release of adriamycin from these PDLLA/PEG micelles, and concluded that the drug release from these micelles was mainly 'degradation controlled'.