Protective effects of fentanyl preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion in rats.

We aimed to study the effect of fentanyl (Fen) preconditioning on cardiomyocyte apoptosis induced by ischemia-reperfusion (I/R) in rats. A total of 120 Sprague Dawley male rats (age: 3 months) were randomly divided into: sham operation group (S group), I/R group, normal saline I/R group (NS group), and fentanyl low, middle, and high dose groups (Fen1: 2 µg/kg; Fen2: 4 µg/kg; Fen3: 6 µg/kg). Heart rate (HR), mean arterial pressure (MAP), left ventricular developed pressure (LVDP), ±dp/dtmax, malondialdehyde (MDA), superoxide dismutase (SOD) activity, creatine phosphokinase-MB (CK-MB), and cardiac troponin-I (cTnI) were measured. Myocardial ischemic (MI) area, total apoptotic myocardial cells, and protein and mRNA expressions of B-cell lymphoma 2 (Bcl-2) and Bax were detected. HR and MAP were higher, while LVDP and ±dp/dtmax were close to the base value in the Fen groups compared to those in the I/R group. Decreased MDA concentration and CK-MB value and increased SOD activity were found in the Fen groups compared to the I/R group, while cTnI concentration was significantly lower in the Fen1 and Fen2 groups (all P<0.05). Myocardial damage was less in the Fen groups compared to the I/R group and the MI areas and apoptotic indexes were significantly lower in the Fen1 and Fen2 groups (all P<0.05). Furthermore, significantly increased protein and mRNA expressions of Bcl-2, and decreased protein and mRNA expressions of Bax were found in the Fen groups compared to the I/R group (all P<0.05). Fentanyl preconditioning may suppress cardiomyocyte apoptosis induced by I/R in rats by regulating Bcl-2 and Bax.

Characteristic and controlled release of anticancer drug loaded poly (D,L-lactide) microparticles prepared by spray drying technique.

Anticancer drug release from polylactic acid microspheres prepared by the spray-drying process was studied. Several process parameters and properties of the polymer solution have been investigated. Normal size distributions with diameters ranging from 5-10 microm were obtained by the spray drying technique. The yield of microspheres recovered depended on polymer solution and process conditions employed. Results show that the yield of microspheres could reach 50%, and the experimental drug loading approached the theoretical drug loading. Scanning electron microscopy indicated that microspheres were composed of a dense thin skin layer and porous core. The magnitude of this effect depended on the inlet temperature, feed polymer concentration and air flow rate. Increasing inlet temperature and polymer concentration resulted in an intact particle shape and a slower drug dissolution rate. The in-vitro release of anticancer drug from microspheres was sustained over 7 days. The drug release behaviour depended on inlet temperature, air flow rate, PLA concentration and drug loading. The anticancer drug release rate from polylactic acid microspheres prepared by the spray-drying method was depressed, and the long-acting release could be achieved by appropriate operating parameters.

In vitro evaluation of a chitosan membrane cross-linked with genipin.

The study was to evaluate the characteristics of a chitosan membrane cross-linked with a naturally-occurring cross-linking reagent, genipin. This newly-developed genipin-cross-linked chitosan membrane may be used as an implantable drug-delivery system. The chitosan membrane without cross-linking (fresh) and the glutaraldehyde-cross-linked chitosan membrane were used as controls. The characteristics of test chitosan membranes evaluated were their cross-linking degree, swelling ratio, mechanical properties. antimicrobial activity, cytotoxicity, and degradability. It was found that cross-linking of chitosan membrane using genipin increased its ultimate tensile strength but significantly reduced its strain-at-fracture and swelling ratio. There was no significant difference in antimicrobial activity between the genipin-cross-linked chitosan membrane and its fresh counterpart. Additionally, the results showed that the genipin-cross-linked chitosan membrane had a significantly less cytotoxicity and a slower degradation rate compared to the glutaraldehyde-cross-linked membrane. These results suggested that the genipin-cross-linked chitosan membrane may be a promising carrier for fabricating an implantable drug-delivery system. The drug-release characteristics of the genipin-cross-linked chitosan membrane are currently under investigation.

Fabrication and characterization of a sponge-like asymmetric chitosan membrane as a wound dressing.

A novel asymmetric chitosan membrane has been prepared by immersion-precipitation phase-inversion method and evaluated as wound covering. This new type of chitosan wound dressing which consists of skin surface on top-layer supported by a macroporous sponge-like sublayer was designed. The thickness of the dense skin surface and porosity of sponge-like sublayer could be controlled by the modification of phase-separation process using per-evaporation method. The asymmetric chitosan membrane showed controlled evaporative water loss, excellent oxygen permeability and promoted fluid drainage ability but could inhibit exogenous microorganisms invasion due to the dense skin layer and inherent antimicrobial property of chitosan. Wound covered with the asymmetric chitosan membrane was hemostatic and healed quickly. Histological examination confirmed that epithelialization rate was increased and the deposition of collagen in the dermis was well organized by covering the wound with this asymmetric chitosan membrane. The results in this study indicate that the asymmetric chitosan membrane thus prepared could be adequately employed in the future as a wound dressing.

Porous chitosan microsphere for controlling the antigen release of Newcastle disease vaccine: preparation of antigen-adsorbed microsphere and in vitro release.

Porous chitosan microspheres suitable for the delivery of antigen were prepared using a wet phase-inversion method. The pore structure of the chitosan microsphere could be modified by the change of pH value of the coagulation medium, which is the aqueous tripolyphosphate (TPP) solution. High porosity of chitosan microsphere with an open porous structure on its surface was prepared by coagulation in TPP aq. solution of pH 8.9. The porous chitosan microspheres were modified chemically with reagents to introduce three types of functional groups; carboxyl, hydrophobic acyl and quaternary ammonium groups. Antigen of ND vaccine was immobilized into the pores of porous chitosan microspheres and the adsorbed antigen was assayed by the Hemoglobin Aggregation (HA) analytical method. Sustained-release of ND vaccine's antigen could be achieved through an adsorption-desorption release test. The chemical modifications of the porous chitosan microspheres have a strong large influence on the adsorption efficiency or release rates of the antigen investigated. The porous microspheres have a higher adsorption efficiency and the slower release rate of antigen when modified chemically with 3-chloro-2-hydroypropyltrimethylamonium chloride.

Sustained-release of oxytetracycline from chitosan microspheres prepared by interfacial acylation and spray hardening methods.

Chitosan microspheres containing oxytetracycline (OTC), an antibiotic agent, were prepared by spray hardening and interfacial acylation methods. The object of this study was to prepare oxytetracycline-containing microspheres for oral administration and injection using different molecular weight (Mw 70,000 approximately 2,000,000) of chitosan. By the spray hardening method, microspheres with particle sizes between 5 and 30 microns could be obtained and might be suitable for intramuscular injection. On the other hand, chitosan microspheres with the ability to extend the dissolution period of oxytetracycline in low pH medium were also prepared by the interfacial acylation method. The result indicated that the releasing of oxytetracycline from various acylated chitosan microspheres was decreased with increasing the molecular weight of chitosan and would show well sustained-release property. Besides, the morphology of various microspheres and crystalline form transition of oxytetracycline were also studied using electron scanning microscope and X-ray analysis.

Preparation and release properties of biodegradable chitin microcapsules: II. Sustained release of 6-mercaptopurine from chitin microcapsules.

Chitin microcapsules are prepared using a simple desolvation or nonsolvent addition phase separation method with 6-mercaptopurine (6-MP) as a reference core. Chitin with a molecular weight about 400,000 is used to prepare different core loaded microcapsules. The drug release rates of chitin microcapsules prepared by simple desolvation or nonsolvent addition method have different release profiles which are related to the rate of phase separation. With respect to the solubility parameter difference (delta delta) value between solvent and nonsolvent, the release rate of 6-MP from microcapsules decreases with increasing delta delta of the preparative system. The chitin beads show poor swelling properties and their release rates are pH-dependent. Sustained release of 6-MP from chitin microcapsules in low pH and neutral medium can be accomplished. To determine if the drug release from the polymer matrix is via a diffusion controlled or by an erosion controlled process, 6-MP release profiles of various chitin microcapsules degraded by lysozyme are investigated. The drug-release patterns of the chitin microcapsules prepared by nonsolvent addition (acetone, n-propanol, n-butanol) and simple desolvation in acetone are not only diffusion but also lysozyme digestion influenced. Whereas, by using water or ethanol as nonsolvent or desolvating agent, release profiles of the microcapsules prepared by nonsolvent addition and the simple desolvation method seem to be little affected by enzyme degradation. These results indicate that chitin might prove useful as a polymer carrier for the sustained release of drugs.

Preparation and release properties of biodegradable chitin microcapsules: I. Preparation of 6-mercaptopurine microcapsules by phase separation methods.

Chitin [poly-(N-acetyl-1,4-beta-D-glucopyranosamine)] microcapsules were prepared by the simple desolvation and the non-solvent addition phase separation methods. In the simple desolvation method, chitin droplets were dropped into the desolvation agent (water, ethanol, or acetone) and microcapsules soon formed. Several solvent-nonsolvent pairs: N,N-dimethylacetamide (DMAc)-water, DMAc-ethanol, DMAc-propanol, DMAc-n-butanol, and DMAc-acetone with different solubility parameter difference, (delta delta) were chosen to prepare chitin microcapsules containing 6-mercaptopurine by using the non-solvent-addition phase separation method. The results showed that the surface morphology and release behaviour of the microcapsules were greatly affected by different solvent-nonsolvent pairs. The surface of microcapsules prepared from the system of high delta delta was more smooth than those from the systems of low delta delta. The drug content using the simple desolvation method increased with decreasing delta delta because of the higher film formation rate of the microcapsules. On the other hand, the drug content using the nonsolvent addition method was lower than that using the simple desolvation method because of the dispersion forces, applied by mechanical stirring. Microcapsules prepared by the simple desolvation method had a narrower size distribution and larger mean size than those prepared by the nonsolvent addition method.