Co-delivery of simvastatin and microRNA-21 through liposome could accelerates the wound healing process.

The gene delivery approach, mainly microRNAs (miRNA) as key wound healing mediators, has recently received extensive attention. MicroRNA-21 (miR-21) has strongly impacted wound healing by affecting the inflammation and proliferation phases. Previous studies have also demonstrated the beneficial effect of simvastatin on wound healing. Therefore, we designed a dual-drug/gene delivery system using PEGylated liposomes that could simultaneously attain the co-encapsulation and co-delivery of miRNA and simvastatin (SIM) to explore the combined effect of this dual-drug delivery system on wound healing. The PEG-liposomes for simvastatin and miR-21 plasmid (miR-21-P/SIM/Liposomes) were prepared using the thin-film hydration method. The liposomes showed 85 % entrapment efficiency for SIM in the lipid bilayer and high physical entrapment of miR-21-P in the inner cavity. In vitro studies demonstrated no cytotoxicity for the carrier on normal human dermal fibroblast cells (NHDF) and 97 % cellular uptake over 2 h incubation. The scratch test revealed excellent cell proliferation and migration after treatment with miR-21-P/SIM/Liposomes. For the in vivo experiments, a full-thickness cutaneous wound model was used. The wound closure on day 8 was higher for Liposomal formulation containing miR-21-P promoting faster re-epithelialization. On day 12, all treated groups showed complete wound closure. However, following histological analysis, the miR-21-P/SIM/Liposomes revealed the best tissue regeneration, similar to normal functional skin, by reduced inflammation and increased re-epithelialization, collagen deposition and angiogenesis. In conclusion, the designed miR-21-P/SIM/Liposomes could significantly accelerate the process of wound healing, which provides a new strategy for the management of chronic wounds.

Improved infectious burn wound healing by applying lyophilized particles containing probiotics and prebiotics.

Lactiplantibacillus plantarum cells were encapsulated in a mixture of cationic and anionic polymers, with the final composition stabilized through freeze-drying. A D-optimal design was used to examine the effects of different polymer concentrations as well as adding prebiotics on the probiotic viability and swelling behavior of the formulations. Scanning electron micrographs revealed stacked particles capable of rapidly absorbing significant amounts of water. These images corresponded to initial swelling percentages of around 2000% for the optimal formulation. The optimized formula had a viability percentage of more than 82%, with the stability studies suggesting that the powders should be stored at refrigerated temperatures. The physical characteristics of the optimized formula were examined to ensure compatibility with its application. According to antimicrobial evaluations, the difference in pathogen inhibition between formulated and fresh probiotics was less than a logarithm. The final formula was tested in vivo and showed improved wound healing indicators. The optimized formula resulted in a higher rate of wound closure and infection clearance. Furthermore, the molecular studies for oxidative stress indicated that the formula could modify wound inflammatory responses. In histological investigations, the probiotic-loaded particles functioned exactly as efficaciously as silver sulfadiazine ointment did.

Novel biodegradable molecularly imprinted polymer nanoparticles for drug delivery of methotrexate anti-cancer; synthesis, characterization and cellular studies.

BACKGROUND: Recently biodegradable nanoparticles are the center of attention for the development of drug delivery systems. Molecularly imprinted polymer (MIP) is an interesting candidate for designing drug nano-carriers. MIP-based nanoparticles could be used for cancer treatment and exhibited the potential to fill gaps regarding to ligand-based nanomaterials. Also, the presence of a cross-linker can play an essential role in nanoparticle stability and physicochemical properties of nanoparticles after synthesis. OBJECTIVES: In this research, a biodegradable drug delivery system based on MIP nanoparticles was prepared using a biodegradable cross-linker (dimethacryloyl hydroxylamine, DMHA) for methotrexate (MTX). A hydrolysable functional group CO-O-NH-CO was added to the crosslinking agent to increase the final biodegradability of the polymer. METHODS: Firstly, a biodegradable cross-linker was synthesized. Then, the non-imprinted polymers were prepared through mini-emulsion polymerization in the absence of a template; and efficient particle size distribution was determined. Finally, methotrexate was placed in imprinted polymers to achieve the desired MIP. Different types of MIPs were synthesized using different molar ratios of template, cross-linker, and functional monomer, and the optimal molar ratio was obtained at 1:4:20, respectively. RESULTS: HNMR successfully confirmed the chemical structure of the cross-linker. According to SEM images, nanoparticles had a spherical shape with a smooth surface. The imprinted nanoparticles showed a narrow size distribution with an average of 120 nm at a high ratio of cross-linker. The drug loading and entrapment efficiency were 6.4% and 92%, respectively. The biodegradability studies indicated that the nanoparticles prepared by DMHA had a more degradability rate than ethylene glycol dimethacrylate as a conventional cross-linker. Also, the polymer degradation rate was higher in alkaline environments. Release studies in physiological and alkaline buffer showed an initial burst release of a quarter of loaded MTX during the day and a 70% release during a week. The Korsmeyer-Peppas model described the release pattern. The cytotoxicity of MTX loaded in nanoparticles was studied on the MCF-7 cell line, and the IC50 was 3.54 µg/ml. CONCLUSION: It was demonstrated that nanoparticles prepared by DMHA have the potential to be used as biodegradable drug carriers for anticancer delivery. Synthesis schema of molecular imprinting of methotrexate in biodegradable polymer based on dimethacryloyl hydroxylamine cross-linker, for use as nanocarrier anticancer delivery to breast tumor.

In Vitro-In Vivo Correlation for the Antibacterial Effect of Lactiplantibacillus plantarum as a Topical Healer for Infected Burn Wound.

Difficulties in delivering antimicrobial agents to wound areas and emersion of multiple drug resistant organisms (MDROs) have converted managing burn infections into a complicated task in medicine. Probiotics emerged not only as a probable solution for burn infections but also as an accelerator in the healing process. The probability of in vitro-in vivo correlation (IVIVC) in probiotic activity leads to lower costs in finding new therapeutic options. Simulated wound fluid (SWF) was used to evaluate the antibacterial function of Lactiplantibacillus plantarum in wounds. The growth parameters in SWF were evaluated using a logistic model to predict growth behavior in the wound area. In addition, probiotic antimicrobial activity and secretion of antibacterial substances in SWF were also studied. Data were used to select the initial dose and apply frequency for in vivo study. The wound models were infected by two main pathogens (Pseudomonas aeruginosa or Staphylococcus aureus). In vitro results showed less lag time associated with considerable acid production in SWF. In the following, secretion of antimicrobial substances and co-aggregation with pathogens became more important. The susceptibility of pathogens to these factors was different, and culture medium affected the yield of each factor involved in eliminating pathogens. Histological analysis and macroscopic examination of wounds revealed probiotics as effective as positive control or more. There were some differences in the antibacterial functions of probiotics in simulated and real wound environments. The in vitro effect of probiotics on removal of pathogens was not the same as the trend seen in vivo.

Crosslinked-polyvinyl alcohol-carboxymethyl cellulose/ZnO nanocomposite fibrous mats containing erythromycin (PVA-CMC/ZnO-EM): Fabrication, characterization and in-vitro release and anti-bacterial properties.

Recently, nanocomposite nanofibers have been extensively used for biomedical applications. It is expected that simultaneous incorporation of antibiotic drugs and ZnO nanoparticles into nanofiber resulted in providing the synergistic anti-bacterial effect. The main aim of the present study is to fabricate polyvinyl alcohol (PVA)/carboxymethyl cellulose (CMC)-ZnO nanocomposite fibrous mats containing erythromycin (EM) drug and crosslink them using 2% glutaraldehyde vapor and 3% AlCl3 alcoholic solution. The fabricated nanofibers characterized via TGA, FTIR, TEM, and SEM, indicating that the addition of ZnO nanoparticles and EM molecules into the fabricated nanofibers resulted in changing their average diameter. Their anti-bacterial activity was studied against S. aureus and E. coli and found that PVA-CMC/ZnO-EM nanofibers show excellent antimicrobial activity. In-vitro release profile showed that EM release from PVA-CMC/ZnO-EM nanofibers was slowly increased. Sustained drug release profile and excellent anti-bacterial activity of PVA-CMC/ZnO-EM nanofiber indicated that it was an ideal biomaterial for wound dressings.

Simultaneous Determination of Nine Sunscreen Agents by HPLC and Chemometric Analysis.

A worldwide outbreak of skin cancer, related to ultraviolet (UV) radiations, was reported. Therefore, primary prevention programs were initiated. Application of sunscreens is one of the most efficient ways of protection; however, their efficiency and safety have remained a challenging issue. So, it seems necessary to consider the potential side effects for limiting the use and amount of sunscreens. In this study, an high performance liquid chromatography (HPLC) system equipped with a UV-visible detector has been used. For separation, an Agilent C18 column was used (Agilent Technologies, Santa Clara, CA). This method was applied for quantitative determination of nine UV filters in commercial sunscreen products which were widely used in Iran. Fifty samples of Iranian and imported sunscreen products were analyzed. The detection limit was determined to be 0.439-1.481 µg/ml, and the quantization limit was determined to be 1.330-4.490 µg/ml. Also, in this study, chemometric methods were used to investigate the differences between Iranian and other countries' sunscreen brands. It was observed that despite the amount of UV filters in Iranian sunscreens, which was in the allowed range, there were some differences between Iranian and other countries' sunscreens. The proposed HPLC method allows efficient and simultaneous analysis of UV filters and is suitable as a quality control assay for commercial sunscreen products.