الفهرس 
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Abstract
This present study was held to improve wound healing process using natural products as curcumin and propolis with nanotechnology application.
Hydro-alcoholic extraction of propolis was conducted for purity and getting rid of residues. The extraction produced a brown mass of propolis with a yield of 21.1%.
Emulsion-evaporation-solidification technique was used for formation of curcumin and propolis NLCs. This method composed of two phases, organic and aqueous, that were heated at 70℃ for melting lipids in the mixture and reducing the solvent and water content. Glycerol mono-stearate (GMS) and capric acid were considered as the lipids of organic phase. This blending of lipids enhanced curcumin and propolis loading capacity and minimized their expulsion during storage. Lecithin and Tween 80 acted as homogenizer, stabilizer, and surfactant agents yielding semi-solid nano-emulsions that undergo sonication and gelatinization for topical application.
Detection of size and shape of particles of nano-structured lipid carriers formed using scanning electron microscope that showed irregular spherical particles with different sizes for curcumin while uniform elliptical particles for propolis and transmission electron microscope that confirmed the formation of particles with compatible morphology as shown on SEM. Also, demonstrating entrapment efficiency, drug loading and zeta potential charge that indicated long-term stable dispersions had high ZP value.
In accordance with the role of phenolic and flavonoid compounds at the respiratory burst of neutrophils, during the inflammatory phase, experiments were held to determine those compounds content at curcumin, propolis and their nano-formulations. Total phenolic content was measured by Folin-Ciocalteau method and results were expressed as g per g tannic acid but for total flavonoids, they were expressed as g per g rutin equivalents. While the anti-oxidant activity were estimated by detecting the DPPH radical scavenging activity.
Disc diffusion method was used to reveal the antimicrobial activity and minimal inhibitory concentration using five bacterial strains which were Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Salmonella spp., Staphylococcus aureus ATCC 25923 and Staphylococcus epidermis and one culture of fungal strain namely, Candida albicans EMCC 105 were used according to their availability and relation to animal wound infection. All used strains in this study kindly provided from American Type Culture collection (ATCC), USA.
Twenty-Four male rabbits (New Zealand) weighting between 1.9-2 Kg were divided into four groups (n=6). Each group studied different form of gel as group I “curcumin gel”, group II “nano-curcumin gel”, group III “propolis gel” and group IV “nano-propolis gel”.
where each rabbit had two full thickness skin excision (3 x 3 cm2 ) on its dorsum receiving on the right side one of the formed treatment gels (Curcumin, nano-curcumin, propolis and nano-propolis) and a blanked gel on the left side as a control wound for seven days afterward the surgery.
The wounds followed up for three weeks. The percentage of wound healing detected at the 7th, 14th and 21st days. Control wounds were of average 32.28 ± 0.068%, 67.27 ± 0.059% and 87.49 ± 0.01%. Curcumin and nano-curcumin were 51.62 ± 0.09%, 60.39 ± 0.04% for the 7th day and 88.91 ± 0.04%, 93.73 ± 0.04% at the 14th day, while by the 21st day they possessed complete healing. After the first week, the propolis group and nano-propolis group percentages were 48.68 ± 0.051% and 55.97 ± 0.066%. Then the second week, they were 79.97 ± 0.058% and 90.03 ± 0.052%. The third week they possessed 97.36 ± 0.005% and 99.19 ± 0.012%.
Tissue sections, collected at the 7th, 14th and 21st days of wound excisions, fixed in formalin solution. Then, staining them with haematoxylin and eosin (H&E) stain for histological evaluations.
Wound evaluation indicates that the best gel formulations in this trial were curcumin gel and nano-curcumin gel as they accelerated the healing of the wound in comparison with propolis gel and nano-propolis gel that incompletely healed by the 14th day. While the control negative group was in the early stage of healing, so the use of nano-technology potent the bioavailability and efficiency of both curcumin and propolis.
SO, the use of curcumin gel and nano-curcumin gel in natural topical healing formulations with minimum scaring is recommended.