Development of nano-liposomal human growth hormone as a topical formulation for preventing uvb-induced skin damage.

Due to its involvement in skin maintenance and repair, topical administration of recombinant human growth hormone (rhGH) is an interesting strategy for therapeutic purposes. We have formulated and characterized a topical rhGH-loaded liposomal formulation (rhGH-Lip) and evaluated its safety, biological activity, and preventive role against UVB-induced skin damage. The rhGH-Lip had an average size and zeta potential of 63 nm and -33 mV, respectively, with 70 % encapsulation efficiency. The formulation was stable at 4 °C for at least one year. The SDS-PAGE and circular dichroism results showed no structural alterations in rhGH upon encapsulation. In vitro, studies in HaCaT, HFFF-2, and Ba/F3-rhGHR cell lines confirmed the safety and biological activity of rhGH-Lip. Franz diffusion cell study showed increased rhGH skin permeation compared to free rhGH. Animal studies in nude mice showed that liposomal rhGH prevented UVB-induced epidermal hyperplasia, angiogenesis, wrinkle formation, and collagen loss, as well as improving skin moisture. The results of this study show that rhGH-Lip is a stable, safe, and effective skin delivery system and has potential as an anti-wrinkle formulation for topical application. This study also provides a new method for the topical delivery of proteins and merits further investigation.

Nanocrystal Structure of Minoxidil: A Safe Stimulator for Hair Growth Factor for C57BL/6 Mice.

BACKGROUND: Commercial Minoxidil (MXD) is commonly used as a vasodilator agent of hair follicles for providing direct dermal papilla cell proliferation and consequently enhancing the rate of hair growth. OBJECTIVE: The current study attempted to improve the bioactivity and water solubility of MXD by producing nanocrystal structures and investigating the obtained hair growthstimulating activity on C57BL/6 mice. METHOD: The MXD nanoparticles (MXD-NPs) were prepared through a bead mill and ultrasonic process and characterized by DLS, XRD, UV-Vis, FTIR, FESEM, TEM, and Zeta-potential techniques. RESULT: The cytotoxicity of MXD-NPs was studied on human dermal fibroblast (HDF) by MTT assay. Lastly, we analyzed the comparative hair growth inductive activity of certain MXD-NPs concentrations on C57BL/6 mice. The stabled MXD-NPs (-46 mV, 21.9 nm) caused a significant increase in the hair growth rate of C57BL/6 mice by running a safe site-specific delivery mechanism on the targeted pilosebaceous follicles when compared to MXD. CONCLUSION: The MXD-NPs-receiving mice exhibited a greater rate of anagen/telogen follicular when compared with MXD-treated types, which verified the improvement of their hair re-growing and follicular-stimulative activities. Therefore, these outcomes confirmed the potential of MXD-NPs for substituting its commercial solution format as a safe and efficient iso-formulation structure.

Comparative effect of triamcinolone/lidocaine ultrasonophoresis and injection on pain, disability, quality of life in patients with acute rotator cuff related shoulder pain: a double blinded randomized controlled trial.

BACKGROUND: Alleviating inflammation should be considered as one of the first steps of the treatment plan in patients with acute rotator cuff related shoulder pain (RCRSP). OBJECTIVE: To compare the effects of triamcinolone/lidocaine ultrasonophoresis, injection on pain, disability, and quality of life in patients with acute RCRSP. METHODS: A total of 28 acute RCRSP patients were randomly allocated into two groups of ultrasonophoresis and injection. Both groups received vitamin C and shoulder care education for 10 days and then were subjected to therapeutic interventions. Ultrasonophoresis group received triamcinolone (16 mg) and lidocaine (2mg) using ultrasonophoresis (frequency: 3 MHz, intensity: 1.50 W/Cm2), while the injection group received a single subacromial injection of triamcinolone (80 mg) and lidocaine (10 mg). The main outcomes measures were pain assessed by two scales (visual analog scale), and shoulder pain and disability index (SPADI), disability (SPADI), and quality of life (Western Ontario rotator cuff questionnaire). RESULTS: Although the main effect of time was statistically significant for all dependent variables (P< 0.01), no significant interaction was found between group and time (P-value (0.12-0.55)). The ultrasonophoresis effect, size for pain, disability, and quality of life were 2.58, 1.43, 1.78, and 1.35, respectively. The injection effect, size for pain, disability, and quality of life were 1.98, 2.02, 1.40, and 1.60, respectively. CONCLUSIONS: Triamcinolone/lidocaine ultrasonophoresis demonstrated similar outcomes to injection in reducing pain, improving disability, and enhancing quality of life in patients with acute RCRSP in short time. According to our findings, ultrasonophoresis with triamcinolone/lidocaine cream is as effective as triamcinolone/lidocaine injection and can be proposed as a potential adjunctive treatment for patients with acute RCRSP.

Preparation and characterization of solid lipid nanoparticles encapsulated noscapine and evaluation of its protective effects against imiquimod-induced psoriasis-like skin lesions.

Psoriasis is a chronic inflammatory skin disease characterized by thickening the epidermis with erythema, scaling, and proliferation. Noscapine (NOS) has several anti-inflammatory, anti-angiogenic, and anti-fibrotic effects, but its low solubility and large size results in its lower efficacy in the clinic. In this regard, solid lipid nanoparticles (SLN) encapsulated NOS (SLN-NOS) were fabricated using the well-known response surface method based on the central composite design and modified high-shear homogenization and ultrasound method. As a result, Precirol® was selected as the best lipid base for the SLN formulation based on Hildebrand-Hansen solubility parameters, in which SLN-NOS 1 % had the best zeta potential (-35.74 ± 2.59 mV), average particle size (245.66 ± 17 nm), polydispersity index (PDI, 0.226 ± 0.09), high entrapment efficiency (89.77 %), and ICH-based stability results. After 72 h, the SLN-NOS 1 % released 83.23 % and 58.49 % of the NOS at pH 5.8 and 7.4, respectively. Moreover, Franz diffusion cell's results indicated that the skin levels of NOS for SLN and cream formulations were 46.88 % and 13.5 % of the total amount, respectively. Our pharmacological assessments revealed that treatment with SLN-NOS 1 % significantly attenuated clinical parameters, namely ear thickness, length, and psoriasis area and severity index, compared to the IMQ group. Interestingly, SLN-NOS 1 % reduced the levels of interleukin (IL)-17, tumor necrosis factor-α, and transforming growth factor-ß, while elevating IL-10, compared to the IMQ group. Histology studies also showed that topical application of SLN-NOS 1 % significantly decreased parakeratosis, hyperkeratosis, acanthosis, and inflammation compared to the IMQ group. Taken together, SLN-NOS 1 % showed a high potential to attenuate skin inflammation.

Preparation, Characterization, and Molecular Dynamic Simulation of Novel Coenzyme Q10 Loaded Nanostructured Lipid Carriers.

BACKGROUND: Research proved that coenzyme Q10-loaded NLC effectively removes skin wrinkles, therefore, such a formulation with good characteristics is still the research goal. OBJECTIVE: This study investigated the effect of solid lipids and surfactant type on the physical characteristics of Q10-NLC. We aimed to achieve the optimum formulation for producing NLC with long-term stability and high Entrapment efficiency (E.E.) %. We compared the experimental results with the output of the Molecular dynamic (M.D.) simulations. METHODS: To develop Q10-NLC, various solid lipids, MCT oil, and surfactants were employed. The formulations were prepared by high-shear homogenization and ultrasound methods. Stability studies were carried out 1,3, and 6 months at 4, 25, and 40°C. The optimized NLC formulations were characterized by photon correlation spectroscopy (PCS), Transmission electron microscopy (TEM), Differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR). E.E. % was determined by HPLC analysis. Atomistic M.D. simulations of two model systems were performed to gain insights into the self-assembled process of co-Q10 with other formulation components. RESULTS: Statistical analysis (Two-way ANOVA) revealed that solid lipid and surfactant factors had a significant influence on particle size, PDI, and zeta potential (***p < 0.0001). According to the results, F1 and F6 formulations had desirable surface characterizations, physicochemical stability, and high E.E. %. The atomistic M.D. simulations confirmed that the F1 system (best) was more stable than the F31 system (worst). CONCLUSION: The solid lipids: tripalmitin and compritol, stabilized with 4% tween 80 and 1% span 80, have produced stable NLC with the best surface characteristics that could be a promising formulation for the delivery of Q10. Atomistic M.D. simulation has confirmed the stability of F1 in comparison to F31.

The potential therapeutic impact of a topical bacteriophage preparation in treating Pseudomonas aeruginosa-infected burn wounds in mice.

Aim: This study compared a topical formulation containing lytic phages with a routine antibiotic in the murine model of burn/Pseudomonas aeruginosa infected wound healing. Methods & Materials: Isolated and purified lytic bacteriophages from hospital sewage were added to the polyethylene glycol (PEG) based ointment. A second-degree burned wound on the back of twenty-four adult female mice was created. The wounds were infected subcutaneously with 100 µL of 1 × 102-3 CFU/mL P. aeruginosa. After 24 h, mice were randomly assigned to one of four groups: mice received a standard antibiotic (antibiotic-treated group), mice received an ointment without bacteriophage (PEG-based group), mice received a PEG-ointment with bacteriophage (bacteriophage-treated group), or mice received no treatment (untreated-control group). Every two days, the contraction of burned wounds, physical activity, and rectal body temperature were recorded. On day 10, mice were sacrificed, and the wounds were cut off and evaluated histopathologically. Results: In ointments containing PEG, bacteriophages were active and stable. The mice receiving bacteriophage and PEG-based ointment had substantially different wound contraction in primary wound healing (P = 0.001). When compared to the control group, the bacteriophage-treated group showed significant variations in wound contraction (P = 0.001). The wound contraction changed significantly between the antibiotic and PEG-based groups (P = 0.002). In all groups, physical activity in mice improved over time, with significant differences (P = 0.001). When the 8th day was compared to the days 2, 4, and 6, significant changes were found (P = 0.001, P = 0.02, and P = 0.02, respectively). Both the positive control and bacteriophage-treated groups showed perfect wound healing histopathologically. However, no significant variations in microscopic histopathological criteria were found between the groups. Conclusion: Formulated phage ointment could be a promising approach for treating infected burn wounds infected by P. aeruginosa in mice with no allergic reactions.

Preparation and Characterization of Undecylenoyl Phenylalanine Loaded-Nanostructure Lipid Carriers (NLCs) as a New α-MSH Antagonist and Antityrosinase Agent.

Purpose: The aim of this study was to characterize the undecylenoyl phenylalanine (Sepiwhite (SEPI))-loaded nanostructured lipid carriers (NLCs) as a new antimelanogenesis compound. Methods: In this study, an optimized SEPI-NLC formulation was prepared and characterized for particle size, zeta potential, stability, and encapsulation efficiency. Then, in vitro drug loading capacity and the release profile of SEPI, and its cytotoxicity were investigated. The ex vivo skin permeation and the anti-tyrosinase activity of SEPI-NLCs were also evaluated. Results: The optimized SEPI-NLC formulation showed the size of 180.1±5.01 nm, a spherical morphology under TEM, entrapment efficiency of 90.81±3.75%, and stability for 9 months at room temperature. The differential scanning calorimetry (DSC) analysis exhibited an amorphous state of SEPI in NLCs. In addition, the release study demonstrated that SEPI-NLCs had a biphasic release outline with an initial burst release compared to SEPI-EMULSION. About 65% of SEPI was released from SEPI-NLC within 72 h, while in SEPI-EMULSION, this value was 23%. The ex vivo permeation profiles revealed that the higher SEPI accumulation in the skin following application of SEPI-NLC (up to 88.8%) compared to SEPI-EMULSION (65%) and SEPI-ETHANOL (74.8%) formulations (P<0.01). An inhibition rate of 72% and 65% was obtained for mushroom and cellular tyrosinase activity of SEPI, respectively. Moreover, results of in vitro cytotoxicity assay confirmed SEPI-NLCs to be non-toxic and safe for topical use. Conclusion: The results of this study demonstrate that NLC can efficiently deliver SEPI into the skin, which has a promise for topical treatment of hyperpigmentation.

Prevention of radiotherapy-related oral mucositis with zinc and polyherbal mouthwash: a double-blind, randomized clinical trial.

BACKGROUND: A significant percentage of head and neck cancer (HNCs) patients receiving RT experience oral mucositis (OM). This study aimed to evaluate the effect of the polyherbal (containing chamomile, peppermint oil, Aloe vera, and honey) and zinc mouthwashes in comparison to the control (chlorhexidine) and placebo groups for prevention of radiation-induced OM. METHODS: This study was a double-blinded randomized clinical trial, conducted on 67 patients with HNCs undergoing radiotherapy. The eligible participants were randomized to receive either one of the following; zinc sulfate, polyherbal, chlorhexidine (Vi-one 0.2% CHX), or placebo mouthwash for 6 weeks. Follow-up evaluation of oral hygiene and the checklists of OM and the intensity of pain were filled out according to WHO assessment tool, Oral Mucositis Assessment Scale (OMAS), and Visual Analog Scale (VAS) in all the participants weekly for seven consecutive weeks. RESULTS: The results of present clinical trial demonstrated that the use of either zinc sulfate or polyherbal mouthwash significantly reduced the scores of OM and the severity of pain during weeks 2 to 7 after consumption compared with the CHX or placebo mouthwashes (P < 0.05). According to the post hoc analysis and compared with the placebo, a significantly better result was reported for zinc sulfate and polyherbal mouthwashes at weeks 2 to 7, but not for the CHX mouthwash. CONCLUSION: This study showed that the use of zinc sulfate or polyherbal mouthwashes is effective in prevention of both OM severity scores and pain related to OM intensity at weeks 2 to 7 following consumption in HNCs patients. Trial registration IRCT20190123042475N1 and IRCT20190123042475N2. Registration date: 2019-06-09, 2019-07-26.

The recent advancements in the early detection of cancer biomarkers by DNAzyme-assisted aptasensors.

Clinical diagnostics rely heavily on the detection and quantification of cancer biomarkers. The rapid detection of cancer-specific biomarkers is of great importance in the early diagnosis of cancers and plays a crucial role in the subsequent treatments. There are several different detection techniques available today for detecting cancer biomarkers. Because of target-related conformational alterations, high stability, and target variety, aptamers have received considerable interest as a biosensing system component. To date, several sensitivity-enhancement strategies have been used with a broad spectrum of nanomaterials and nanoparticles (NPs) to improve the limit and sensitivity of analyte detection in the construction of innovative aptasensors. The present article aims to outline the research developments on the potential of DNAzymes-based aptasensors for cancer biomarker detection.

Preparation, characterization, and evaluation of anti-tyrosinase activity of solid lipid nanoparticles containing Undecylenoyl phenylalanine (Sepiwhite®).

BACKGROUND: Hyperpigmentation is darkened patches or spots on the skin occurred by increased melanin. Undecylenoyl phenylalanine (Sepiwhite®), as a commercial lipophilic derivative of phenylalanine, is a powerful new brightener that can be used in the treatment of skin pigmentation disorders. AIMS: Solid lipid nanoparticles (SLNs) increase the efficiency of hydrophobic drugs. The current study aimed to prepare and characterize SLNs containing Sepiwhite (SEPI-SLN). METHODS: In this study, an optimized SEPI-SLN formulation was selected by applying the response surface method. In vitro drug loading content, the release profile of SEPI, and cell viability were investigated. The permeation rate of SEPI-SLN was also compared to conventional cream containing Sepiwhite (SEPI-CREAM). Furthermore, the anti-tyrosinase activity of Sepiwhite was also evaluated. RESULTS: The optimized formulation showed a spherical morphology with particle size and entrapment efficiency of 218.6 ± 11.1 nm and % 87.31 ± 0.65, respectively. Differential scanning calorimetry (DSC) analysis confirmed SEPI-loaded SLN formulation with no drug-lipid incompatibility. The in vitro permeation experiment revealed the enhanced cutaneous uptake of SEPI-SLN. The results also showed that Sepiwhite could stop melanogenesis with inhibition of the tyrosinase enzyme. CONCLUSION: Our findings confirm that SLNs could be a proper nanocarrier for the relevant usage of Sepiwhite as a powerful brightener agent.

Preparation and Characterization of Nanostructured Lipid Carrier (NLC) and Nanoemulsion Containing Vitamin D3.

Vitamin D is an essential vitamin for bone marrow development and immune function, which is mostly synthesized in the skin through sun exposure. The high global prevalence of vitamin D deficiency requires a feasible approach to administer vitamin D to a larger number of population in a shorter amount of time, and this may be achieved through food fortification. Food fortification using nanostructured lipid carriers (NLC) and nanoemulsions appears to be an ideal method to enhance bioavailability, stability, and solubility of bioactive compounds. The aim of this study was to develop NLC and nanoemulsion forms of vitamin D to evaluate its efficacy for further enrichment of dairy products. NLC containing Precirol and nanoemulsion containing vegetable oils were prepared and characterized for polydispersity index, particle size, zeta potential, particle shape, crystal properties, stability, encapsulation efficiency, and releasing. Vitamin D3 NLC size was in the range of 123.4 to 210.6 nm and for nanoemulsion 137.6 to 171.6 nm, respectively. Optimal NLC and nanoemulsion carriers were selected for morphological assessment, encapsulation efficiency, thermal analysis, and release study. Scanning and transmission electron microscopy revealed that particles had approximately spherical shape. In gastric simulated solution (pH = 1.2), NLC and nanoemulsion form of vitamin D3 released 9.3% and 26.9% of vitaminD3, respectively. This indicated that our formulation is able to protect vitamin D3 under acidic conditions. The results of this study revealed that NLC and nanoemulsion could be an optimal carrier for food fortification in order to improve bioavailability of bioactive compounds such as vitamin D.

Noscapine, an Emerging Medication for Different Diseases: A Mechanistic Review.

Noscapine is a benzylisoquinoline alkaloid isolated from poppy extract, used as an antitussive since the 1950s, and has no addictive or euphoric effects. Various studies have shown that noscapine has excellent anti-inflammatory effects and potentiates the antioxidant defences by inhibiting nitric oxide (NO) metabolites and reactive oxygen species (ROS) levels and increasing total glutathione (GSH). Furthermore, noscapine has indicated antiangiogenic and antimetastatic effects. Noscapine induces apoptosis in many cancerous cell types and provides favourable antitumour activities and inhibitory cell proliferation in solid tumours, even drug-resistant strains, via mitochondrial pathways. Moreover, this compound attenuates the dynamic properties of microtubules and arrests the cell cycle in the G2/M phase. Noscapine can reduce endothelial cell migration in the brain by inhibiting endothelial cell activator interleukin 8 (IL-8). In fact, this study aimed to elaborate on the possible mechanisms of noscapine against different disorders.

Implementation of design of experiments for optimization of forced degradation conditions and development of a stability-indicating high-performance liquid chromatography method for sepiwhite.

Sepiwhite is a novel anti-pigmenting agent that is derived from fatty acid and phenylalanine and used for hyperpigmentation induced by light exposure or inflammation. In this study, a simple and validated high-performance liquid chromatography method for the quantitation of sepiwhite was developed. Optimized forced degradation of sepiwhite at thermal, acid/base, photolysis, oxidative, and heavy metal ions conditions were evaluated and the effect of each of them on production of specific 10%-30% degradants was studied by the approach of design of experiments. Sepiwhite accelerated study was conducted and toxicity of sepiwhite at each condition was tested. An optimized high-performance liquid chromatography method was validated by a face-centered central composition design. Ten different degradants were identified from sepiwhite and degradation behavior under different conditions was studied. Sepiwhite and its degradant products show no cytotoxicity. This optimized high-performance liquid chromatography method can be applied for quality control assay and sepiwhite degradation behavior may be considered in the manufacturing of sepiwhite products.

Moisturizing effects of solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using deionized and magnetized water by in vivo and in vitro methods.

OBJECTIVES: The present study aimed to determine and compare moisturizing and occlusion effects of different solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) using magnetized water and deionized water. MATERIALS AND METHODS: SLN formulations were prepared using various lipids, including Tripalmitin, Compritol®, Precirol®, and emulsifiers including Poloxamer and Tween 80. NLC formulations were also prepared with oleic acid and the same solid lipids. Two types of formulations were prepared; first with deionized water and then with magnetized water. Formulations were prepared using high shear homogenization and ultrasound methods. The products were analyzed by PSA (particle size analyzer), DSC (differential scanning calorimetry), and TEM (transmission electron microscopy). The moisturizing effect of formulations was determined by in vivo and in vitro methods. RESULTS: Findings of the assessments demonstrated that in products prepared with magnetized water, 5% SLN Precirol® had the most moisturizing effect in vivo and 5% SLN Compritol® had the most moisturizing effect in vitro. The use of magnetized water in formulations can improve the effectiveness and increase the stability of moisturizing products. CONCLUSION: In this study, all products prepared with magnetized water showed more stability, smaller size, and more moisturizing effects compared with products prepared with deionized water.

Preparation and characterization of stable nanoliposomal formulations of curcumin with high loading efficacy: In vitro and in vivo anti-tumor study.

Liposomal formulations were made using Solvent-assisted active loading technology (SALT). Two formulations composed of HSPC:DPPG:Chol:DSPE-mPEG2000 (PG-LipCUR) and HSPC:Chol:DSPE-mPEG2000 (LipCUR) demonstrated good colloidal properties and the CUR-encapsulation of 82% and 89% for PG-LipCUR and LipCUR, respectively. The results showed that both formulations were stable during 6 months storage at 4 °C. The release study showed that the PG-LipCUR and LipCUR formulations are relatively stable at pH 7.4. Both formulations had higher cytotoxicity on TUBO and 4T1 cell lines in compassion with normal cells. PG-LipCUR had the higher amounts of CUR cellular uptake than LipCUR. Biodistribution studies showed that both formulations could enhance the half-life of the CUR 2-3 times compared to free CUR. The tumor accumulation of PG-LipCUR was significantly higher than LipCUR. The antitumor activities of liposomes on 4T1 tumor model demonstrated the efficacy of both formulations compared to PBS and free CUR. PG-LipCUR also was more potent in tumor growth delay in comparison with LipCUR. However, combination of the Caelyx® and PG-LipCUR had the most antitumor properties among other treatments. Based on the results, PG-LipCUR could be a promising formulation for the delivery of CUR which also significantly increased the efficacy of Caelyx® and merits further investigation.

Development, characterization and evaluation of topical methotrexate-entrapped deformable liposome on imiquimod-induced psoriasis in a mouse model.

The aim of this study was to prepare and characterize topical methotrexate (MTX) with different percentages (0.05%, 0.1%, 0.25% and 0.5%) entrapped in deformable liposomes using phosphatidylcholine and oleic acid. The effectiveness and sub-acute toxicity of these topical formulations were investigated in imiquimod (IMQ)-induced psoriasis in a mouse model (IMQP). The particle sizes of formulations were around 100 nm with a mean zeta potential of -72.87 mV. The entrapment efficiency (EE%) of MTX in liposomal formulations were more than 85%. Franz cell permeability studies indicated that permeation of MTX through the healthy BALB/c mice skin is very low; however, in the inflammatory skin, which was induced by IMQ it was significant (50%). Liposomal MTX (LM 0.05 and 0.1%) caused significant reduction of thickness score dose-dependently in IMQP compared to the injected MTX. Moreover, investigation of the inflammatory factor and pathological examinations of skin proved the superiority of the LM treating group. Pathological examinations also showed there are no toxicity in organs of the mice that received the LM. Blood cell count test didn't show any abnormality. MTX-entrapped deformable liposomes could be a topical option in future for the treatment of human psoriasis with a less toxicity and merit further investigations.

Formulation, clinical and histopathological assessment of microemulsion based hydrogel for UV protection of skin.

The aim of this study was to prepare a microemulsion based hydrogel containing sesame oil and evaluate its topical application in preventing the harmful effects of UV radiation on the guinea pig's skin using histopathologic and clinical findings. Sesame oil with high antioxidant content and unique chemical and physiological properties is a suitable candidate for the evolution of UV protection on skin. Applying this natural oil in microemulsion formulation containing particles with nanometer size can enhance its efficacy. To prepare a stable microemulsion, it is necessary to select the appropriate surfactants. In this study, first the best combination of hydrophilic surfactant of Tween 80 with various lipophilic surfactants such as Span 20, Span 80 and Span 85 at different surfactant ratios was examined. The microemulsion formulations were assessed for particle size, zeta potential, polydispersity index, refractive index, electrical conductivity, pH value and stability. Results showed that among various samples, microemulsion containing a mixture of Tween 80 and Span 80 with the surfactant ratio of 9:1 was the best sample in terms of stability over time (six months). This sample had a lower particle size of 26.09 nm with a narrow particle size distribution. For topical application, the microemulsion based hydrogel was prepared with 0.6% Carbomer 940 as a gelling agent. The pH value and viscosity of gel formulation were 6.6 and 12.90 Pa.s, respectively, which is appropriate for topical applications. A slight enhancement of particle size inside hydrogel structure was observed after six months of the gel preparation. The clinical evolutions of formulation on guinea pig's skin were included skin scaling, skin irregularity, erythema, skin hyperpigmentation, and edema. Epidermal hyperkeratosis, hyperpigmentation, exocytosis, acanthosis, chromatin discoloration in nucleus of epidermal squamous cells, perifolliculitis, dermal vascular hyperemia, edema and dermal thickness, infiltration of plasma cell lymphocytes and eosinophils into dermis were observed for histopathological investigations. Based on clinical and histopathological examinations, topical application of microemulsion-based hydrogel of sesame oil can effectively prevent skin damage induced by UV radiation and is therefore suitable for skin products.

Influence of main emulsion components on the physicochemical and functional properties of W/O/W nano-emulsion: Effect of polyphenols, Hi-Cap, basil seed gum, soy and whey protein isolates.

In this study, the effect of natural macromolecules as carrier agents on the biological activity of nano-encapsulated Bene hull polyphenols (Pistacia atlantica subsp. Mutica) through W/O/W emulsions was evaluated. The W/O microemulsions as primary emulsions and a complex of soy protein isolate and basil seed gum (SPI-BSG), whey protein isolate and basil seed gum (WPI-BSG) and also Hi-Cap 100 in the outer aqueous phase were used to produce W/O/W nano-emulsions. Z-average size of emulsions stabilized by Hi-Cap, WPI-BSG, and SPI-BSG was 318, 736.9 and 1918 nm, respectively. The encapsulation efficiency of polyphenols for powders produced by Hi-Cap, WPI-BSG, and SPI-BSG was 95.25, 90.9 and 92.88%, respectively, which was decreased to 72.47, 67.12 and 64.44% after 6 weeks storage at 30 °C. The antioxidant activity of encapsulated polyphenols at 100, 200 and 300 ppm was measured in oil by peroxide and p-anisidine values during storage and was compared to non-encapsulated extract and synthetic antioxidant. Results showed oxidative alterations in oils containing encapsulated polyphenols was lower than unencapsulated form, which among them capsules produced by SPI-BSG exhibited higher antioxidant effects due to the better gradual release. Generally, the higher antioxidant potential was achieved with increased solubility and controlled release of polyphenols through their nano-encapsulation.

Preparation, characterization, and optimization of auraptene-loaded solid lipid nanoparticles as a natural anti-inflammatory agent: In vivo and in vitro evaluations.

Auraptene (AUR) is a bioactive antioxidant coumarin with valuable pharmacological properties; however, poor water solubility is a substantial issue for the topical application of AUR. Therefore, we sought to prepare solid lipid nanoparticles (SLNs) containing AUR (AUR-SLNs) to enhance its anti-inflammatory effect. The prepared formulations were optimized by applying the response surface method. Furthermore, AUR-SLNs were compared to conventional cream containing AUR regarding both the permeation rate of the nanoparticles and the anti-inflammatory effect through both in vitro and in vivo studies. Particle size and entrapment efficiency of the optimized formulation were 140.9 ±â€¯3.55 nm and 84.11% ±â€¯3.30, respectively. Transmission electron microscopy revealed that the nanoparticles were spherical. Differential scanning calorimetry (DSC) analysis demonstrated no drug-lipid incompatibility in the formulation. Fourier transform-infrared spectroscopy (FTIR) spectra revealed the amorphous state of AUR and the encapsulation of this agent in SLNs. The in vitro permeation studies exhibited that AUR-SLNs could significantly enhance cutaneous uptake of AUR and skin targeting. The anti-inflammatory and histopathological studies exhibited no significant differences between AUR-SLNs and indomethacin. AUR-SLNs did not induce skin sensitization in guinea pigs. The results suggest that SLNs could be appropriate carriers for the topical application of AUR as a natural anti-inflammatory agent.

Encapsulation challenges, the substantial issue in solid lipid nanoparticles characterization.

Solid lipid nanoparticles (SLNs), as alternative colloidal carriers, have been used for the sustained release of lipophilic drugs with poor water solubility. One of the most important parameters in the characterization of SLNs is entrapment efficiency (EE). Despite the importance of this factor in estimating the drug loading capacity, EE does not always represent the exact percentage of the entrapped drug. Several variables such as the stirring speed and duration, and concentration of surfactant, emulsifier, and drug play important roles in determining the final EE. In addition, EE is mainly affected by the type and concentration of the lipid. There are two major methods for the measurement of EE are in which the encapsulated drug in SLNs is either directly measured (direct method) or the amount of unencapsulated drug in the supernatant is measured (indirect method). Accuracy of drug analysis is the main challenge for EE calculation, and is either performed in the separated aqueous medium or the particles. In this review, we aimed to introduce the available methods for EE determination in SLNs and discuss the advantages and shortcomings of each method.