Curcumin-Loaded Mesoporous Silica Particles as Wound-Healing Agent: An In vivo Study.

BACKGROUND: Curcumin likely has wound-healing properties, but its poor pharmacokinetic attributes inhibit its potential. To overcome these limitations, a novel nanoformulation was previously developed, wherein curcumin was loaded into mesoporous silica particles. OBJECTIVES: The objective of the study is to assess the efficiency of this nanocurcumin formulation as a wound-healing agent in an animal model. MATERIALS AND METHODS: Curcumin was loaded onto mesoporous silica particles. Eighteen healthy, test-naive male Wistar rats were randomly separated into two groups of 9: Group 1 (control) rats were treated topically with a standard drug (sulfadiazine) and Group 2 with 1% curcumin formulation. A circular excision wound was made, and topical application was performed twice a day. The excision diameters were measured on days 3, 6, 9, 12, 15, 18 and 21 of treatment. Three rats from each group were sacrificed on days 7, 14 and 21, and a cross-section from skin specimen in the excision injury was obtained for histological assessment of inflammation, angiogenesis, fibroblast proliferation, presence of collagen and reepithelization. RESULTS: Wound contraction percentage in rats treated with curcumin nanoformulation was nonsignificantly higher than that in the control group (P > 0.05). In both groups, inflammatory reactions considerably reduced by day 21 of treatment, the angiogenesis process was almost complete by day 7, fibroblast proliferation noticeably rose by day 14, and a high degree of wound reepithelization was achieved by day 21, with no significant differences between the groups. Interestingly, by day 21, the level of collagen significantly increased in curcumin nanoformulation-treated rats compared with those treated with sulfadiazine. CONCLUSIONS: Curcumin nanoformulation likely enhanced wound repair by inhibiting the inflammatory response, stimulating angiogenesis, inducing fibroblast proliferation as well as enhancing reepithelization and synthesis of collagen. Therefore, the curcumin nanoformulation used in this study may have potential as a wound-healing ethnomedicine.

Anti-angiogenic activity of Middle East medicinal plants of the Lamiaceae family.

Angiogenesis plays a crucial role in malignant tumor progression and development. The present study aimed to identify lead plants with selective anti-angiogenic properties. A total of 26 methanolic extracts obtained from 18 plants growing in Saudi Arabia and Jordan that belong to the Lamiaceae family were screened for their cytotoxic and anti-angiogenic activities using MTT and rat aortic ring assays, respectively. Four novel extracts of Thymbra capitata (L.) Cav., Phlomis viscosa Poir, Salvia samuelssonii Rech.f., and Premna resinosa (Hochst.) Schauer were identified for their selective anti-angiogenic effects. These extracts did not exhibit cytotoxic effects on human endothelial cells (EA.hy926) indicating the involvement of indirect anti-angiogenic mechanisms. The active extracts are potential candidates for further phytochemical and mechanistic studies.

Pharmacological activities of a novel plant species, Huernia Sp. Nov. aff. Boleana growing in the high mountains of southwest Saudi Arabia.

Huernia Sp. Nov. aff. Boleana, Apocynaceae, grows in the high mountains of southwest Saudi Arabia and is widely used as a remedy for the treatment of diabetes. The present study investigated the anti­inflammatory, wound healing and inhibitory effects on migration of Huernia Sp. Nov. aff. Boleana. The anti­inflammatory effect was assessed in mice using formalin­induced edema. Wound healing effects were assessed in rats using a circular excision wound model. An in vitro 'scratch' test was used to investigate the inhibitory effects on melanoma cell (B16­F10) migration. The anti­inflammatory effects of total extract, hexane and chloroform fractions were greater or equal to indomethacin (control). The relatively non­polar fractions (hexane and chloroform) exhibited higher anti­inflammatory activities compared with the aqueous fraction. The percentage of wound contraction among animals treated with the plant extract was higher compared with the control; however, this difference was not statistically significant (P>0.05). The total plant extract increased wound healing by inhibiting the inflammatory response, promoting angiogenesis, and significantly promoting the proliferation of fibroblasts, particularly on days 7 and 14 post­wounding. Furthermore, the plant extract promoted wound repair via the enhancement of collagen synthesis, and complete epithelization with well­formed and differentiated epithelial tissues. The in vitro 'scratch' test indicated the inhibitory effects of this plant on melanoma cell migration in a dose­dependent manner. The present study indicated that Huernia Sp. Nov. aff. Boleana may have potential as an anti­inflammatory, wound-healing and migration-inhibiting ethno medicine.

The association of eating habits and lifestyle with overweight and obesity among health sciences students in Taif University, KSA.

OBJECTIVES: This work investigated the impacts of food habits and lifestyle on the prevalence of overweight (OW) and obesity (OB) among health sciences students (HSS) at Taif University, KSA. METHODS: A cross-sectional survey was conducted with 228 HSS in a university setting using a food frequency questionnaire. Body mass index (BMI) was used to assess weight gain, and waist circumference (W_C) was employed for the assessment of abdominal adiposity. RESULTS: The prevalences of OW and OB were 25.9% and 10.9%, respectively, with an overall prevalence of 36.8%. All demographic variables had an insignificant (P > 0.05) effect on W_C. There were significant links between gender, academic year and discipline and BMI (P < 0.05). Smoking, stress, duration of TV viewing, daylight and night sleep had an effect on BMI and W_C but were statistically insignificant (P > 0.05). Breakfast, light meals, eating with a family, fast food, and regular and diet soft drinks had insignificant impacts on BMI (P > 0.05). A considerable relationship was observed between consumption of liver and BMI (P < 0.05), while meat, egg, milk, fruit and vegetable, and grain intake had no significant effect on BMI (P > 0.05). All varieties of foods had no significant impact on W_C (P > 0.05). CONCLUSIONS: The prevalence of OW and OB was 36.8%. The participants' gender, academic year, discipline, and liver intake had a significant impact on BMI. All other tested variables showed a nonsignificant relationship with W_C.

Quality by design approach to prepare oleoyl alginate derivative and its use in transdermal delivery.

The aim of this study is to prepare an optimized surface active modified polysaccharide gel of oleoyl alginate using response surface methodology as well as to study its potential use in drug skin delivery as a safe alternative to skin penetration enhancers. An optimized oleoyl alginate material was obtained using response surface methodology in terms of three different responses, i.e. degree of substitution, viscosity and surface tension. The resultant optimized oleoyl alginates were further studied concerning particle size, surface roughness and particle aggregation concentration measurements. Franz diffusion cell method was used to monitor skin permeation of ibuprofen lysinate over 6-h period exposure to excised rabbit skin. The optimized oleoyl alginate based on surface tension showed the highest particle size, the lowest surface tension among other preparations and it has also been used as skin penetration enhancer for ibuprofen lysinate. In this study, a polysaccharide derivative was prepared that enhanced skin penetration ability of the model drug i.e. ibuprofen lysinate.

General public knowledge, perceptions and practice towards pharmaceutical drug advertisements in the Western region of KSA.

This study aims to examine general public knowledge and behavior toward pharmaceutical advertisements in the Western part of KSA. A cross sectional convenience sampling technique was used in this study. A total of 1445 valid questionnaires were received and analyzed using SPSS version 16 at alpha value of 0.05. Majority of respondents were aware of different types of drugs to be advertised and drug advertisements should seek approval from the health authorities. Television and Internet showed the highest effect on consumers. Almost half of the participants preferred an advertised drug over non-advertised one. Most of the respondents indicated that the quality of frequently advertised drugs is not better than those prescribed by the doctors. Majority of participants had positive beliefs toward advertised drugs concerning their role in education and spreading of awareness among the public. Pharmaceutical advertisements harm the doctor-patient relationship as evidenced by one-third of the investigated sample. Moreover, majority of the participants mentioned that they would consult another doctor or even change the current doctor if he/she refused to prescribe an advertised medication. Results of this study could be used to develop awareness programs for the general public and try to enforce the regulations and policies to protect the general public and patients from the business oriented pharmaceutical companies and drug suppliers.

Acidolysis of tristearin with selected long-chain fatty acids.

Five lipases, namely, Candida antarctica (Novozyme-435), Mucor miehei (Lipozyme-IM), Pseudomonas sp. (PS-30), Aspergillus niger (AP-12), and Candida rugosa (AY-30), were screened for their effect on catalyzing the acidolysis of tristearin with selected long-chain fatty acids. Among the lipases tested C. antarctica lipase catalyzed the highest incorporation of oleic acid (OA, 58.2%), gamma-linolenic acid (GLA, 55.9%), eicosapentaenoic acid (EPA, 81.6%), and docosahexaenoic acid (DHA, 47.7%) into tristearin. In comparison with other lipases examined, C. rugosa lipase catalyzed the highest incorporation of linoleic acid (LA, 75.8%), alpha-linolenic acid (ALA, 74.8%), and conjugated linoleic acid (CLA, 53.5%) into tristearin. Thus, these two lipases might be considered promising biocatalysts for acidolysis of tristearin with selected long-chain fatty acids. EPA was better incorporated into tristearin than DHA using the fifth enzymes. LA incorporation was better than CLA. ALA was more reactive than GLA during acidolysis, except for the reaction catalyzed by Pseudomonas sp., possibly due to structural differences (location and geometry of double bonds) between the two fatty acids. In another set of experiments, a combination of equimolar quantities of unsaturated C18 fatty acids (OA + LA + CLA + GLA + ALA) was used for acidolysis of tristearin to C18 fatty acids at ratios of 1:1, 1:2, and 1:3. All lipases tested catalyzed incorporation of OA and LA into tristearin except for M. miehei, which incorportaed only OA. C. rugosa lipase better catalyzed incorporation of OA and LA into tristearin than other lipases tested, whereas the lowest incorporation was obtained using Pseudomonas sp. As the mole ratio of substrates increased from 1 to 3, incorporation of OA and LA increased except for the reaction catalyzed by A. niger and C. rugosa. All lipases tested failed to allow GLA or CLA to participate in the acidolysis reaction, and ALA was only slightly incoporated into tristearin when M. miehei was used.

Acidolysis reactions lead to esterification of endogenous tocopherols and compromised oxidative stability of modified oils.

For the first time, a possible mechanism responsible, in part, for the removal of endogenous antioxidants through the formation of tocopheryl esters during acidolysis reactions is proposed and confirmed. Tocopherols in the oils were found to react with carboxylic acids present in the medium, thus leading to the formation of tocopheryl esters that do not render any stability to the resultant modified oils as they lack any free hydroxyl groups on the phenolic ring of the molecule. Tocopheryl oleate, used as a standard, was synthesized through the reaction of acyl chloride of oleic acid with alpha-tocopherol (m/z 695.5 as evidenced by mass spectrometry). Subsequently, lipase-assisted esterification of alpha-, gamma-, and delta-tocopherols with oleic acid was carried out, and corresponding tocopheryl esters were isolated. In a real acidolysis reaction system involving docosahexaenoic acid single-cell oil and capric acid, high-performance liquid chromatography-mass spectrometry analysis demonstrated the presence of several tocopheryl esters. These included tocopheryl esters of myristic acid, namely, alpha-tocopheryl myristate, m/z 641.1, gamma-tocopheryl myristate, m/z 627.1, and delta-tocopheryl myristate, m/z 613.1, as well as those of palmitic acid, namely, alpha-tocopheryl palmitate, m/z 669.1, gamma-tocopheryl palmitate, m/z 655.1, and delta-tocopheryl palmitate, m/z 641.1. The mixture also contained different species of tocopheryl oleates, namely, alpha-tocopheryl oleate, m/z 695.5, gamma-tocopheryl oleate, m/z 681.1, and delta-tocopheryl oleate, m/z 667.2. Esters produced from reactions of docosahexaenoic acid and tocopherols were also detected, namely, alpha-tocopheryl docosahexaenoate, m/z 738.7, and delta-tocopheryl docosahexaenoate, m/z 710.7.

Synthesis of structured lipids containing medium-chain and omega-3 fatty acids.

The ability of different lipases to incorporate omega3 fatty acids, namely, eicosapentaenoic acid (EPA, C20:5n-3), docosapentaenoic acid (DPA, C22:5n-3), and docosahexaenoic acid (DHA, C22:6n-3), into a high-laurate canola oil, known as Laurical 35, was studied. Lipases from Mucor miehei (Lipozyme-IM), Pseudomonas sp. (PS-30), and Candida rugosa (AY-30) catalyzed optimum incorporation of EPA, DPA, and DHA into Laurical 35, respectively. Other lipases used were Candida anatrctica (Novozyme-435) and Aspergillus niger (AP-12). Response surface methodology (RSM) was used to obtain a maximum incorporation of EPA, DPA, and DHA into high-laurate canola oil. The process variables studied were the amount of enzyme (2-6%), reaction temperature (35-55 degrees C), and incubation time (12-36 h). The amount of water added and mole ratio of substrates (oil to n-3 fatty acids) were kept at 2% and 1:3, respectively. The maximum incorporation of EPA (62.2%) into Laurical 35 was predicted at 4.36% of enzyme load and 43.2 degrees C over 23.9 h. Under optimum conditions (5.41% enzyme; 38.7 degrees C; 33.5 h), the incorporation of DPA into high-laurate canola oil was 50.8%. The corresponding maximum incorporation of DHA (34.1%) into Laurical 35 was obtained using 5.25% enzyme, at 43.7 degrees C, over 44.7 h. Thus, the number of double bonds and the chain length of fatty acids had a marked effect on the incorporation omega3 fatty acids into Laurical 35. EPA and DHA were mainly esterified to the sn-1,3 positions of the modified oils, whereas DPA was randomly distributed over the three positions of the triacylglycerol molecules. Meanwhile, lauric acid remained esterified mainly to the sn-1 and sn-3 positions of the modified oils. Enzymatically modified Laurical 35 with EPA, DPA, or DHA had higher conjugated diene (CD) and thiobarbituric acid reactive substance (TBARS) values than their unmodified counterpart. Thus, enzymatically modified oils were more susceptible to oxidation than their unmodified counterparts, when both CD and TBARS values were considered.

Synthesis of structured lipids via acidolysis of docosahexaenoic acid single cell oil (DHASCO) with capric acid.

Screening of five commercially available lipases for the incorporation of capric acid (CA) into docosahexaenoic acid single cell oil (DHASCO) indicated that lipase PS-30 from Pseudomonas sp. was most effective. Of the various reaction parameters examined, namely, the mole ratio of substrates, enzyme amount, time of incubation, reaction temperature, and amount of added water, for CA incorporation into DHASCO, the optimum conditions were a mole ratio of 1:3 (DHASCO/CA) at a temperature of 45 degrees C, and a reaction time of 24 h in the presence of 4% enzyme and 2% water content. Examination of the positional distribution of fatty acids on the glycerol backbone of the modified DHASCO with CA showed that CA was present mainly in the sn-1,3 positions of the triacylglycerol (TAG) molecules. Meanwhile, DHA was favorably present in the sn-2 position, but also located in the sn-1 and sn-3 positions. The oxidative stability of the modified DHASCO in comparison with the original DHASCO, as indicated in the conjugated diene values, showed that the unmodified oil remained relatively unchanged during storage for 72 h, but DHASCO-based structured lipid was oxidized to a much higher level than the original oil. The modified oil also attained a considerably higher thiobarbituric acid reactive substances value than the original oil over the entire storage period. However, when the oil was subjected to the same process steps in the absence of any enzyme, there was no significant difference (p > 0.05) in its oxidative stability when compared with enzymatically modified DHASCO. Therefore, removal of antioxidants during the process is primarily responsible for the compromised stability of the modified oil.

Production and stability of structured lipids from algal oils and capric acid.

This study aimed to incorporate capric acid (CA) into selected algal oils, namely arachidoinc acid single cell oil (ARASCO), docosahexaenoic acid single cell oil (DHASCO) and the OMEGA-GOLD oil rich in dcosahexaenoic acid (DHA) and dosapentaenoic acid (n-6 DPA). Response surface methodology indicated that under optimum conditions (12.3% enzyme, 45 degrees C, and 29.4 h) CA incorporation was 20.0% into ARASCO; (4.2% enzyme, 43.3 degrees C, and 27.1 h) 22.6% into DHASCO and (2.5% enzyme, 46.6 degrees C and 25.2 h) 20.7% into the OMEGA-GOLD oil. Stereospecific analysis indicated that in all oils examined CA was mainly located at the sn-1 and sn-3 positions of the resultant TAG molecules while the highly unsaturated fatty acids being primarily esterified to the sn-2 positions of the three oils. In all cases, enzymatically modified oils were more susceptible to oxidation than their unmodified counterparts.