Zelihagül Değim

An investigation on skin wound healing in mice with a taurine-chitosan gel formulation.

Summary. The process of wound healing begins immediately following surface lesions or just after exposure to radiation, chemical agents or extreme temperatures.Taurine (2-aminoethane sulfonic acid), an amino acid containing sulfur, is found in almost all tissues in mammals, playing various important physio-logical roles in each organ. Taurine exhibits an antioxidant effect and is also known to have effects on cell proliferation, inflammation and collagenogenesis. Many antioxidants have been used to eliminate the negative effects of oxygen free radicals on wound healing.The objective of the present study was to examine the wound healing effect in mice of taurine-chitosan gel, which releases taurine slowly over a long time period. Fifty mM of taurine in 1.5% chitosan polymer (TAU-GEL) and 1.5% chitosan polymer (CHI-GEL) were applied to full thickness skin wounds of mice once a day for seven days. After seven days of treatment, lipid peroxide formation-malondialdehyde (MDA) and hydroxyproline (HPX) levels and the tensile strength of wound tissues were measured. All results were compared with those of the untreated control group (CONT). The structural alterations in the skin layers were also histologically investigated.It was found that locally administered TAU-GEL form significantly increased wound tensile strength by decreasing the MDA and increasing HPX levels. These results were supported by histological findings. All observations suggest that taurine gel may be effective in wound healing.

Use of microparticulate systems to accelerate skin wound healing

Rapid and proper healing is important in the treatment of skin wounds. The dressing achieves the functions of the natural skin by protecting the wound area from the bulk loss of tissue and creating an effective barrier to outside contaminants without increasing the bacterial load on the wound surface. There are many wound dressings available on the market which can be used in the healing process. Different dressings have been used according to the condition of the wound and the phases of wound healing. Biodegradable polymers are being widely used in drug delivery and also in wound healing. These polymers that are applicable as a wound dressing protect the wound site against unwanted external effects, inhibit wound contraction, and, if possible, stimulate the healing process. Micro- and nanoparticulates are currently being evaluated as a potential drug delivery in clinical applications. Growth factors also play a vital role in wound healing. Polymers used in wound healing act as sustained release vehicles for growth factors. Controlled release of growth factors from microspheres has provided a higher degree of healing in the wound areas. This review is intended to provide information regarding the various formulations and microparticulate systems used in wound healing.

Evaluation of chitosan gel containing liposome-loaded epidermal growth factor on burn wound healing.

The objective of this study is to develop a chitosan gel formulation containing liposomes loaded with epidermal growth factor (EGF) and to evaluate their effects on the healing of second‐degree burn wounds in rats by immunohistochemical, histochemical and histological methods. EGF‐containing multilamellar liposomes which were carried in chitosan gel, EGF gel and EGF‐loaded liposome formulations were prepared. The in vivo experiments were performed on female Sprague Dawley rats. Second‐degree standard burn wounds were formed on rats and liposomes containing 10 µg/ml EGF in 2% chitosan gel, EGF‐chitosan gel and EGF‐loaded liposome formulations were applied daily to the burn wounds and biopsies were taken at the 3rd, 7th and 14th day of the treatment. When the results were evaluated immunohistochemically, there were significant increases in cell proliferation observed in the EGF‐containing liposome in chitosan gel (ELJ) formulation applied group (P < 0·001). The histochemical results showed that the epithelisation rate in the ELJ group was the highest compared with the other group results (P < 0·001). The histological results indicated and supported these findings and faster epithelisation was observed in the ELJ group compared with the other groups.

New perspective for the treatment of Alzheimer diseases: Liposomal rivastigmine formulations

The aim of this study was to determine the transportations of rivastigmine containing from various liposome formulations through Madin Darby Canine Kidney (MDCK) cells monolayer and to compare the in vitro test results with in vivo. There is no other liposome formulation of rivastigmine and the transportations of rivastigmine through MDCK cell monolayers or related study available in the literature. Cytotoxicity (MTT) test was used to determine cell viabilities. The effect of sodium-taurocholate or dimethyl-beta-cyclodextrine as penetration enhancer was also investigated. Characterization and stability studies for liposome formulations were performed. Permeation experiments of rivastigmine were performed through MDCK cells and dialysis membrane. The kinetic of release from liposomes was also investigated. The highest apparent permeability coefficient (log. values) was obtained with sodium-taurocholate liposomes for −1.15 ± 0.16 for MDCK cell. Rivastigmine liposomes and solutions were also administered to mice orally and intraperitonally. Acetylcholinesterase (AChE) activity was determined by Ellman method. AChE% inhibition values were calculated for both blood and brain after administration of rivastigmine solution and liposomes. The highest AChE inhibition was observed for rivastigmine-sodium-taurocholate liposomes. Histological observations of the mice’ brains were performed under transmission electron microscope (TEM). The histological results were also indicated and supported all these findings.

Rectal and vaginal administration of insulin–chitosan formulations: An experimental study in rabbits

Insulin is a polypeptide drug and it is degraded by gastrointestinal enzymes, therefore, it cannot be used via oral route readily. There are only parenteral forms available in the market. The aim of this study was to investigate the effect of rectal and vaginal administration of various insulin gel formulations on the blood glucose level as alternative routes in rabbits. Chitosan gel (CH-gel) was used as a carrier; the penetration enhancing effect of sodium taurocholate and dimethyl-β-cyclodextrin (DM-βCD) was also investigated. CH-gel provided longer insulin release. The maximum decreasing effect on blood glucose level was observed with insulin–CH-gel containing 5% DM-βCD. In conclusion, our results indicate that insulin may penetrate well through the rectal and vaginal mucosae from the CH-gel. DM-βCD was also found to be a useful agent to enhance the penetration of insulin through rectal and vaginal membranes.

An investigation of the interfacial interaction between poly(acrylic acid) and glycoprotein

Abstract The swelling behaviour of poly(acrylic acid) microspheres, produced from poly(acrylic acid) crosslinked with maltose, was investigated as a function of time by using a laser diffraction spectrometer. Swelling was also studied in various pH glycoprotein solutions. Microscopy revealed confirmatory evidence of interfacial film formation when microsphere hydration occurred in a pH 5 glycoprotein solution. ATR-FTIR spectroscopy was used to determine the diffusion coefficient of water through the interfacial film existing at the poly(acrylic acid) glycoprotein solution interface. Both processes exhibited a pH dependency with rates decreasing in the sequence pH 7>6>5=4.

Nanoparticle and liposome formulations of doxycycline: Transport properties through Caco-2 cell line and effects on matrix metalloproteinase secretion

Nanoparticle and liposome formulations containing doxycycline or doxycycline and sodium taurocholate (NaTC) were developed in this study. The anticancer effects of doxycycline and penetration properties from those formulations through Caco-2 cell monolayers were investigated. Matrix metalloproteinases (MMPs) have been reported to play a role in the negative prognosis of many malignant tumors including glioblastoma multiforme (GBM). This study is presented to demonstrate that these developed nanoparticle and liposome formulations of doxycycline are capable of inhibiting MMP-2 release from cultured Caco-2 cells. In this study, Caco-2 cells were used as model cell cultures. A MTT test was performed to determine the effect of doxycycline on the viability of Caco-2 cells. Doxycycline nanoparticles were prepared using emulsion polymerization and doxycycline liposomes were prepared using the dry film hydration method. Transport studies of doxycycline through Caco-2 cells were investigated. MMP-2 was found to be inhibited more with doxycycline if NaTC is present in the formulation. NaTC was also found to be useful to increase penetration due to the inhibition of efflux by interacting with p-glycoproteins, in addition to the penetration enhancing effect as a result of opening tight junctions. These developed formulations were proposed to use for the treatment of tumors and GBM.

Nonisothermal stability tests of famotidine and nizatidine

Nonisothermal stability tests have been proposed as an attractive and alternative method to the conventional isothermal stability tests. The stability and the degradation properties of famotidine and nizatidine were investigated using both isothermal and nonisothermal stability test techniques. Linear and logarithmic temperature programs were used and the degradation rate constant and activation energies were calculated using a computer program, which was written in BASIC. Also the advantages and disadvantages of these temperature programs are compared. The method to estimate parameters is based on nonlinear curve fitting the nonisothermal concentration-time-temperature curve equation. The nonisothermal stability test results were compared with the results of isothermal stability tests and similar results were obtained.

Prediction of Permeability Coefficients of Compounds Through Caco-2 Cell Monolayer Using Artificial Neural Network Analysis

Artificial neural network (ANN) analysis was used to predict the permeability of selected compounds through Caco-2 cell monolayers. Previously reported models, which were shown to be useful in the prediction of permeability values, use many structural parameters. More complex equations have also been proposed using both linear and non-linear relationships, including ANN analysis and various structural parameters. But proposed models still need to be developed using different neuron patterns for more precise predictions and a better understanding of which factors affect the permeation. To develop a simple and useful model or method for easy prediction is also a general need. Permeability coefficients (log kp) were obtained from various literature sources. Some structural parameters were calculated using computer programs. Multiple linear regression analysis (MLRA) was used to predict Caco-2 cell permeability for the set of 50 compounds (r2 = 0.403). A successful ANN model was developed, and the ANN produced log kp values that correlated well with the experimental ones (r2 = 0.952). The permeability of a compound, famotidine, which has not previously been studied, through the Caco-2 cell monolayer was investigated, and its permeability coefficient determined. It was then possible to compare the experimental data with that predicted using the trained ANN with previously determined Caco-2 cell permeability values and structural parameters of compounds. The model was also tested using literature values. The developed and described ANN model in this publication does not require any experimental parameters; it could potentially provide useful and precise prediction of permeability for new drugs or other penetrants.

Caco-2 cell culture as a model for famotidine absorption.

The aim of the study was to determine penetration properties of Famotidine fro the formulations through colon adenocarcinoma (Caco)-2 cell monolayers and to compare in vitro with in vivo test results. It also aimed to determine the effect of particle size on the penetration properties of Famotidine when microsphere formulations were used. Famotidine was chosen as a model drug and Caco-2 cell culture model was used. Biodegradable Famotidine microspheres of poly(lactide-co-glycolide)(PLGA) polymer (50:50) were prepared by using multiple emulsion technique. Microspheres were coded according to their particle size and polymer[LHIV:60 μm Famotidine-PLGA(high viscosity), SHIV:6 μm Famotidine PLGA(high viscosity), LLIV:60 μm Famotidine-PLGA (low viscosity), SLIV:6 μm Famotidine-PLGA (low viscosity)]. Famotidine solution(5 mg/ml) and microsphere formulations were administered orally to mice and blood drug levels were determined and compared with the Caco-2 cell experiments. Permeability values of Famotidine through Caco-2 cells from various formulations were determined (log ksolution = 7, 274 ± 0, 010, log kSHIV = −3, 884 ± 0, 033, log kLHIV = −2, 300 ± 0, 009, log kSLIV = −4, 076 ± 0, 208, log kLLIV = 3, 525 ± 0, 045). Our results showed that H2 receptor antagonists alter the barrier properties of the Caco-2 cell monolayer by causing an increment in the tightness of the tight junctions. Therefore, amount of the H2 receptor antagonist-like drug at the site of action was found to be important as well as polymer type and particle size of microspheres for drug permeation. Permeation of the drug was lower when higher amounts of Famotidine were present at the diffusion site. A controlled release dosage form of H2 receptor antagonist-like drugs may be beneficial for long-term treatments.