Investigating the Changes in Cream Properties Following Topical Application and Their Influence on the Product Efficiency.

Topical products are not stable following application to the skin due to the evaporation of volatile components. Such changes have been demonstrated in liquid emulsions, but there is almost no study available for creams in this respect. The aim of the present investigation is to evaluate the changes in cream properties following topical application and their influence on product efficiency. A method has also been designed and validated to mimic cream application to the skin. To perform this investigation, five different creams were prepared and alterations of type of creams, size of droplets of the dispersed phase, occlusivity, water content and rate of water loss were studied after application. These changes were then attributed to the type of cream, water content, presence of humectant, and time post application. The results demonstrated that creams changed intensely after application, including the phase inversion of O/W formulations, changes in the occlusivity of creams, reduction of water content, rate of water evaporation and droplet size. Such changes could be controlled partly by humectants. The present results suggest that formulators should be aware of such possible changes and required precautions should be taken in advance.

Acetate Kinase a Antisense Delivery by PAMAM Dendrimer for Decreasing Acetate Production and Increasing the Production of Recombinant Albumin in E. coli.

BACKGROUND: Acetate accumulation in the culture medium is known as an inhibitor in recombinant protein production in Escherichia coli. Various approaches have been proposed and evaluated to overcome this challenge and reduce the concentration of acetate. In this study, we examined the effect of acetate kinase A antisense on acetate production rate in E. coli We also used PAMAM dendrimers as a suitable delivery agent for antisense transformation into E. coli host cell. OBJECTIVE: This study aimed to decrease acetate production as a by-product using an antisense-dendrimer complex to increase mass cell and subsequently recombinant Albumin production in E. coli. MATERIALS AND METHODS: Here, to study the effect of this treatment on recombinant protein production, we used pET22b/HAS construct. The ackA gene expression was inhibited by designed antisense to reduce acetate concentration in culture medium. AckA antisense was transferred to E. coli by PAMAM dendrimer. Finally, ackA expression and recombinant Albumin production were evaluated Real-Time PCR and densitometry, respectively. RESULTS: Our data showed, designed antisense lead to reduction of acetate kinase gene expression and subsequently acetate concentration in the culture medium. Finally, acetate concentration reduction and cell mass increase result in enhanced recombinant Alb production in the treated group (1.25 mg.mL-1) compare to the control group ( 0.59 mg.mL-1). CONCLUSIONS: Reduction of acetate in E. coli fermentation process decreased the recombinant Alb production following cell growth and cell mass increase. In the current study, we showed that an antisense can be a useful tool for ackA gene expression reduction. Also, we noted that PAMAM dendrimer could be a proper delivery agent for oligonucleotide antisense transformation into bacterial cells.

The Assessment of Toxicity Characteristics of Cellular Uptake of Paramagnetic Nanoparticles as a New Magnetic Resonance Imaging Contrast Agent.

Nanoparticles are unique that enable many promising medical and technological applications in their physical, and chemical properties. It is widely accepted that nanoparticles should be thoroughly tested for health nanotoxicity, but a moderate risk analysis is currently prevented by a revealing absence of mechanistic knowledge of nanoparticle toxicity. The purpose of this study was to assess in-vitro cytotoxicity of Gadolinium oxide with diethylene glycol polymer (Gd2O3-DEG) and magneto liposome nanoparticles (MLNs) in Hepa 1-6 cell lines as models to assess nanotoxicity in-vitro. The effects of magnetic nanoparticles on these cell lines were evaluated by light microscopy and standard cytotoxicity assays. The underlying interactions of these nanoparticles with physiological fluids are key characteristics of the perception of their biological efficacy, and these interactions can perhaps be performed to relieve unpleasant toxic effects. Our results demonstrated that the Gd2O3-DEG and MLNs had significantlydifferent non-cytotoxic effects. Our results suggest that these cell lines provide valuable models to assess the cytotoxicity of nanoparticles in-vitro. The results of the present study demonstrated that MLNs and Gd2O3-DEG with lower longitudinal relaxation time (T1) than Gadolinium Pentetic acid (Gd-DTPA) in Hepa 1-6 cell lines are sensitive positive Magnetic Resonance Imaging (MRI) contrast agents that could be as attractive as candidates for cellular and molecular lipid content targets such as liver diagnostic applications. These data reveal that MLNs is a useful positive contrast agent for targeting and cell tracking. This will help to image of cells and special organs like liver that uptakes liposomal formulation very well.

Enhanced Production of Insulin-like Growth Factor I Protein in Escherichia coli by Optimization of Five Key Factors.

Human insulin-like growth factor I (hIGF-I) is a kind of growth factor with clinical significance in medicine. Up to now, E. coli expression system has been widely used as a host to produce rhIGF-1 with high yields. Batch cultures as non-continuous fermentations were carried out to overproduce rhIGF-I in E. coli. The major objective of this study is over- production of recombinant human insulin-like growth factor I (rhIGF-I) through a developed process by recruiting effective factors in order to achieve the most recombinant protein. In this study we investigated the effect of culture medium, induction temperature and amount of inducer on cell growth and IGF-1 production. Taguchi design of experiments (DOE) method was used as the statistical method. Analysis of experimental data showed that maximum production of rhIGF-I was occurred in 32y culture medium at 32 °C and 0.05 Mm IPTG. Under this condition, 0.694 g/L of rhIGF-I was produced as the inclusion bodies. Following optimization of these three factors, we have also optimized the amount of glucose and induction time in 5 liter top bench bioreactor. Full factorial design of experiment method was used for these two factors as the statistical method. 10 g/L and OD600=5 were selected as the optimum point of Glucose amount and induction time, respectively. Finally, we reached to a concentration of 1.26 g/L rhIGF-1 at optimum condition.

Changes in morphology of in situ forming PLGA implant prepared by different polymer molecular weight and its effect on release behavior.

The effects of polymer molecular weight on drug release behavior would be more complicated from in situ forming implants (ISFIs) that change gradually from liquid to semi-solid or solid after injection. To investigate this phenomenon, three commercially available D,L-lactic acid-co-glycolic acid (PLGA) polymers with molecular weights of 12, 34, and 48 kDa were used to prepare ISFIs containing leuprolide acetate (LA) as a model peptide. The influence of polymer molecular weight on the membrane formation, morphology, and also on their in vitro drug release behavior over a period of 28 days was investigated. Results showed that the amount of drug released over the first 24 h (36% +/- 0.34%) (burst release), for formulation prepared with polymer RG 503H (medium molecular weight, M(w) 34 kDa), was significantly higher than others (p < 0.05). Surface and cross-section morphology of ISFI prepared with medium molecular weight polymer to cellular and spongy-like structure which was in good agreement with the release behavior of LA from it.

A comparative study of the in vitro permeation characteristic of sulphadiazine across synthetic membranes and eschar tissue.

Infections of burn wounds are the source of significant problems in burn patients. Early excision of eschar tissue is an ideal solution to avoid sepsis. When early excision is not feasible, the application of topical antimicrobial formulations may be used to control burn wound sepsis. An understanding of the barrier properties of eschar tissue is essential for optimal design of topical antimicrobial formulations. To date, little research has been conducted on the permeability of eschar. Silver sulphadiazine (SSD) is the most frequently used topical agent in burn management. In this study, the permeation of sulphadiazine from aqueous saturated solutions of SSD through human full-thickness burn eschar tissue was studied and compared with permeability through silicone and Carbosil as model membranes. The permeation of sulphadiazine through eschar tissue was significantly higher than that through silicone and Carbosil membranes (P < 0.05). Deconvolution of the data showed that the apparent sulphadiazine diffusion coefficient was much higher in eschar tissue and was comparable to transport through an aqueous protein gel. Further studies on a greater number of compounds are suggested to elucidate the utility of such membranes as predictive models of drug permeability through eschar tissue.