pH-sensitive bilayer electrospun nanofibers based on ethyl cellulose and Eudragit S-100 as a dual delivery system for treatment of the burn wounds; preparation, characterizations, and in-vitro/in-vivo assessment.

A pH-sensitive bilayer electrospun nanofibrous mat containing both antibiotic (gentamicin sulfate, GEN) and non-steroidal anti-inflammatory (diclofenac sodium, DIC) drugs was fabricated for burn wound dressing by electrospinning technique, in which ethyl cellulose (EC) and ethyl cellulose/Eudragit S-100 (EC/ES-100) formed the top and bottom layers, respectively. The fabricated pH-sensitive bilayer electrospun nanofibrous mats were characterized from aspects of both structure and efficiency. Physicochemical properties were investigated via SEM, FTIR, and TGA. The swelling ratio and in vitro drug release of the fabricated nanofibrous mats were studied in different pHs. MTT was applied to assess the safety of the fiber mats. Finally, the in vivo efficiency of the designed pH-sensitive bilayer electrospun nanofibrous mats was examined on the male Wistar rats. Based on the histological analysis and wound healing test (in vivo animal experiments), the (ES100/EC-DIC/GEN)-(EC) pH-sensitive bilayer nanofibrous mat displayed faster wound healing than other bilayer nanofibrous mat. As a result, (ES100/EC-DIC/GEN)-(EC) bilayer nanofibrous mat with pH-responsion could accelerate the burn wound healing process via decreasing the adverse effects of GEN and DIC as topical antimicrobial and anti-inflammatory agents, receptively.

Dual drug delivery system based on layered double hydroxides/carboxymethyl cellulose-poly ethylene oxide bionanocomposite electrospun fibrous mats: Fabrication, characterization, in-vitro and in-vivo studies.

The main goal of the present project was to design and develop ibuprofen (IBU) and layered double hydroxides-vancomycin (LDH-VAN) nanohybrid loaded bionanocomposite fibrous mats to increase the wound healing rate. Thus, first, LDH-VAN nanohybrid particles was synthesized by in-situ incorporation of VAN into the Mg-Al-LDH interlayers during the co-precipitation of hydroxides. Then, LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats were fabricated by electrospinning technique. Test samples were examined XRD, SEM, TEM, TGA, and FTIR. In vitro drug release test was performed in the phosphate buffer solution (pH = 7.4) to prove the efficiency of the fabricated bionanocomposite fibrous mats as a sustained-release carrier for both VAN and IBU. All the fabricated bionanocomposite fibrous mats did not displayed any significant cytotoxicity on NIH/3 T3 fibroblast cells. The wound area in the rats treated with LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats was less than other treatment groups. Based on histological analysis, the LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats possess a faster wound healing than other nanofibrous mats. Data obtained from the present project indicated that LDH-VAN/IBU/CMC-PEO bionanocomposite fibrous mats could accelerate the wound healing process.

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.

Development of a T Cell-targeted siRNA Delivery System Against HIV-1 Using Modified Superparamagnetic Iron Oxide Nanoparticles: An In Vitro Study.

In spite of the promising properties of small interfering RNAs (siRNAs) in the treatment of infectious diseases, safe and efficient siRNA delivery to target cells is still a challenge. In this research, an effective siRNA delivery approach (against HIV-1) has been reported using targeted modified superparamagnetic iron oxide nanoparticles (SPIONs). Trimethyl chitosan-coated SPION (TMC-SPION) containing siRNA was synthesized and chemically conjugated to a CD4-specific monoclonal antibody (as a targeting moiety). The prepared nanoparticles exhibited a high siRNA loading efficiency with a diameter of about 85 nm and a zeta potential of +28 mV. The results of the cell viability assay revealed the low cytotoxicity of the optimized nanoparticles. The cellular delivery of the targeted nanoparticles (into T cells) and the gene silencing efficiency of the nanoparticles (containing anti-nef siRNA) were dramatically improved compared to those of nontargeted nanoparticles. In conclusion, this study offers a promising targeted delivery platform to induce gene silencing in target cells. Our approach may find potential use in the design of effective vehicles for many therapeutic applications, particularly for HIV treatment.