Development of solid lipid microparticles (SLMs) containing asiatic acid for topical treatment of acne: Characterization, stability, in vitro and in vivo anti-acne assessment.

Solid lipid microparticles (SLMs) represent a promising approach for drug delivery in anti-acne applications. In this study, asiatic acid-loaded SLMs (AASLMs) were prepared by melt emulsification method in conjunction with freeze-drying. Comprehensive evaluations comprised particle size, %entrapment efficiency (%EE), %labeled amount (%LA), surface morphology, stability, %release, %skin permeation, and anti-acne activity. The AASLMs exhibited an average particle size ranging from 7.46 to 38.86 µm, with %EE and %LA falling within the range of 31.56 to 100.00 and 90.43 to 95.38, respectively. The AASLMs demonstrated a spherical shape under scanning electron microscopy, and maintained stability over a 3-month period. Notably, formulations with 10 % and 15 % cetyl alcohol stabilized with poloxamer-188 (specifically F6 and F12) displayed a minimum inhibitory concentration (MIC) value of 75 mg/ml against Cutibacterium acnes. Furthermore, F12 exhibited a higher %release and %skin permeation compared to F6 over 24 h. In a single-blind clinical trial involving fifteen participants with mild-to-moderate acne, F12 showcased its potential not only in reducing porphyrin intensity and enhancing skin barriers but also in significantly improving skin hydration and brightness. However, further investigations with larger subject cohorts encompassing diverse age groups and genders are necessary to thoroughly establish the performance of the developed AASLMs.

Asiatic acid-entrapped transfersomes for the treatment of hypertrophic scars: In vitro appraisal, bioactivity evaluation, and clinical study.

Non-invasive treatment options for hypertrophic scars (HTS) are limited, and treating HTS remains challenging due to their unappealing appearance and associated social stigma. In this work, a novel transfersomal system named Asiatic acid-entrapped transfersomes (AATs) was prepared. AATs were evaluated for their skin permeability, anti-inflammatory activity, and other characteristic parameters to determine the most promising formulation. Asiatic acid-entrapped transfersomal gel (AATG), which was obtained by incorporating the lead AATs in a gel base, underwent testing in an 8-week, double-blind, placebo-controlled, split-skin clinical study. The net skin elasticity (R5), melanin index (MI), and skin surface hydration were analyzed employing Cutometer®, Mexameter®, and Corneometer®, respectively, in order to evaluate the effectiveness of the developed AATG. AATs exhibited vesicular sizes and zeta potential values within the range of (27.15 ± 0.95 to 63.54 ± 2.51 nm) and (-0.010 to -0.129 mV), respectively. TW80AAT gave the highest %EE (90.84 ± 2.99%), deformability index (101.70 ± 11.59 mgs-1), permeation flux at 8 h (0.146 ± 0.005 mg/cm2/h), and anti-inflammatory activity (71.65 ± 1.83%). The clinical study results of AATG indicated no adverse skin reactions. Furthermore, product efficacy tests demonstrated a significant reduction in MI and an increase in net skin elasticity at 2, 4, and 8 weeks. These pilot study outcomes support the effectiveness of the AATG.

Assessment of in vitro anti-skin aging activities of Phyllanthus indofischeri Bennet extracts for dermatological and aesthetic applications.

Giant Indian Gooseberry (GIG) or Phyllanthus indofischeri Bennet are commercially cultivated and commonly used herbs in Traditional medicine, especially in Thailand. The aim of this study was to assess the potential of the GIG extracts in anti-aging activities to be a dermatological application. The juice, meat residues, and seeds of GIG collected from Sra Kaeo Province, Thailand, were extracted by the Boiling method (B) and the Maceration process (M) by using 95% ethanol as a solvent. The GIG extracts gave the total phenolic, total flavonoid contents and quercetin contents, as well as exhibited anti-oxidative activities. The GIG-R-B extract inhibited tyrosinase activity and had the highest anti-melanogenesis activity on B16F10 cells at 31.63 ± 0.70%. The GIG-S-B, GIG-S-M, and GIG-R-M extracts demonstrated the highest collagen biosynthesis, which was comparable to vitamin C (p < 0.05), whereas the GIG-R-B extracts gave the highest stimulation of anti-aging genes (SIRT1 and FOXO1). All extracts at the concentration of 0.1 mg/mL showed no cytotoxicity on human skin fibroblasts. Therefore, the GIG-S-B extract was discovered to be a promising natural anti-aging agent for dermatological health and aesthetic applications that can be further developed in cosmetic, functional food and food supplement industries.

In vitro anti-ageing activities of ethanolic extracts from Pink rambutan (Nephelium lappaceum Linn.) for skin applications.

Skin ageing is characterized by features such as wrinkles, loss of elasticity, laxity, rough-textured appearance, melasma and freckles. Several researches have focused for preventing, and treating skin ageing by many natural ingredients. This study aimed to assess the anti-ageing activities for anti-skin ageing of the ethanolic extracts of Pink rambutan (PR) (Nephelium lappaceum Linn.) from leaves (L), branches (B), seeds (S), and peels from ripe (R) and young (Y) fruits. The extraction yields of all Pink Rambutan (PR) extracted by the Maceration (M) and the Soxhlet extraction (Sox) using 95% ethanol as a solvent, ranged from 10.62% to 30.63%. Flavonoids were found as the main phytochemicals in almost all the PR extracts. The PR-Y-M and PR-Y-Sox extracts gave the highest total phenolic contents by the Folin-Ciocalteu assay of 67.60 ± 4.38 mgGAE/g, and total flavonoid contents by the modified aluminum chloride colorimetric assay of 678.72 ± 23.59 mgQE/g, respectively. The PR-L-M extracts showed the highest three anti-oxidative activities; the free radical scavenging (SC50 of 0.320 ± 0.070 mg/mL), the lipid peroxidation inhibition (LC50 of 0.274 ± 0.029 mg/mL), and the metal chelation activity (MC50 of 0.203 ± 0.021 mg/mL). All the PR extracts at 0.01 and 0.1 mg/mL showed no cytotoxicity on B16F10 cells, and human skin fibroblasts, respectively. Likewise, the PR-R-Sox extract exhibited the highest anti-melanogenesis on B16F10 cells (52.7 ± 0.9%) and, the mushroom tyrosinase inhibition activity (IC50 of 0.04 ± 0.02 mg/mL), which was significantly comparable to kojic acid (p < 0.05). The PR-Y-Sox extract showed the collagen biosynthesis by the Sirius Red method, and the stimulation of anti-ageing genes (Sirt1 and Foxo1) on human skin fibroblasts by the RT-PCR method, which were similar to standards ʟ-ascorbic acid and resveratrol, respectively. This study suggests that the PR-R-Sox and PR-Y-Sox extracts can be further developed as natural anti-ageing agents for whitening and anti-wrinkle in the cosmetics, cosmeceutical, and pharmaceutical industries.

Regulatory Effects of Thai Rice By-Product Extracts from Oryza sativa L. cv. Bue Bang 3 CMU and Bue Bang 4 CMU on Melanin Production, Nitric Oxide Secretion, and Steroid 5α-Reductase Inhibition.

Alopecia and gray hair are common hair abnormalities affecting physical appearance and causing psychological problems. Chemical treatments partially restore hair disorders but have distressing side effects. Bioactive plant compounds constitute promising sources of potential medicinal substances instead of chemical agents, producing high side effects. In this study, we focused on the waste of local rice cultivars: Bue Bang 3 CMU (BB3CMU) and Bue Bang 4 CMU (BB4CMU) from the north of Thailand. The rice bran oil (RBO), defatted rice bran extract (DFRB), and rice husk (H) were determined for in vitro hair revitalization in melanin production, nitric oxide (NO) secretion, and steroid 5α-reductase inhibition. The results indicated that BB4CMU-RBO with high contents of iron, zinc, and free fatty acids showed a comparable induction of melanin production on melanocytes (130.18 ± 9.13% of control) to the standard drug theophylline with no significant difference (p > 0.05). This promising melanin induction could be related to activating the NO secretion pathway, with the NO secretion level at 1.43 ± 0.05 µM. In addition, BB4CMU-RBO illustrated a significant inhibitory effect on both steroid 5α-reductase genes (SRD5A) type 1 and type 2, which relates to its primary source of tocopherols. Hence, rice bran oil from the Thai rice variety BB4CMU could be applied as a promising hair revitalizing candidate, from natural resources, to help promote hair growth and re-pigmentation effects.

Guava (Psidium guajava L.) Leaf Extract as Bioactive Substances for Anti-Androgen and Antioxidant Activities.

Leaves of guava (Psidium guajava L.) have been used in Thai folk medicine without any supporting evidence as a traditional herbal remedy for hair loss. Androgenetic alopecia (AGA) is chronic hair loss caused by effects of androgens in those with a genetic predisposition, resulting in hair follicle miniaturization. Our objectives were to provide the mechanistic assessment of guava leaf extract on gene expressions related to the androgen pathway in well-known in vitro models, hair follicle dermal papilla cells (HFDPC), and human prostate cancer cells (DU-145), and to determine its bioactive constituents and antioxidant activities. LC-MS analysis demonstrated that the main components of the ethanolic extract of guava leaves are phenolic substances, specifically catechin, gallic acid, and quercetin, which contribute to its scavenging and metal chelating abilities. The guava leaf extract substantially downregulated SRD5A1, SRD5A2, and SRD5A3 genes in the DU-145 model, suggesting that the extract could minimize hair loss by inhibiting the synthesis of a potent androgen (dihydrotestosterone). SRD5A suppression by gallic acid and quercetin was verified. Our study reveals new perspectives on guava leaf extract's anti-androgen properties. This extract could be developed as alternative products or therapeutic adjuvants for the treatment of AGA and other androgen-related disorders.

Preparation, Characterization and Permeation Study of Topical Gel Loaded with Transfersomes Containing Asiatic Acid.

The objective of this study is to investigate the in vitro permeation of asiatic acid (AA) in the form of a topical gel after entrapment in transfersomes by Franz diffusion cells. Transfersomes composed of soybean lecithin and three different edge activators including Tween 80 (TW80), Span 80 (SP80) and sodium deoxycholate (SDC) at the ratio of 50:50, 90:10 and 90:10, respectively, together with 0.3% w/w of AA, were prepared by a high-pressure homogenization technique and further incorporated in gels (TW80AATG, SP80AATG and SDCAATG). All transfersomal gels were characterized for their AA contents, dynamic viscosity, pH and homogeneity. Results revealed that the AA content, dynamic viscosity and pH of the prepared transfersomal gels ranged from 0.272 ± 0.006 to 0.280 ± 0.005% w/w, 812.21 ± 20.22 to 1222.76 ± 131.99 Pa.s and 5.94 ± 0.03 to 7.53 ± 0.03, respectively. TW80AATG gave the highest percentage of AA penetration and flux into the Strat-M® membrane at 8 h (8.53 ± 1.42% and 0.024 ± 0.008 mg/cm2/h, respectively) compared to SP80AATG (8.00 ± 1.70% and 0.019 ± 0.010 mg/cm2/h, respectively), SDCAATG (4.80 ± 0.50% and 0.014 ± 0.004 mg/cm2/h, respectively), non-transfersomal gels (0.73 ± 0.44 to 3.13 ± 0.46% and 0.002 ± 0.001 to 0.010 ± 0.002 mg/cm2/h, respectively) and hydroethanolic AA solution in gel (1.18 ± 0.76% and 0.004 ± 0.003 mg/cm2/h, respectively). These findings indicate that the TW80AATG might serve as a lead formulation for further development toward scar prevention and many types of skin disorders.

A Mini-Review on Solid Lipid Nanoparticles and Nanostructured Lipid Carriers: Topical Delivery of Phytochemicals for the Treatment of Acne Vulgaris.

Acne vulgaris (acne) is one of the most common dermatological problems affecting adolescents and young adults. Although acne may not lead to serious medical complications, its psychosocial effects are tremendous and scientifically proven. The first-line treatment for acne is topical medications composed of synthetic compounds, which usually cause skin irritation, dryness and itch. Therefore, naturally occurring constituents from plants (phytochemicals), which are generally regarded as safe, have received much attention as an alternative source of treatment. However, the degradation of phytochemicals under high temperature, light and oxygen, and their poor penetration across the skin barrier limit their application in dermatology. Encapsulation in lipid nanoparticles is one of the strategies commonly used to deliver drugs and phytochemicals because it allows appropriate concentrations of these substances to be delivered to the site of action with minimal side effects. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) are promising delivery systems developed from the combination of lipid and emulsifier. They have numerous advantages that include biocompatibility and biodegradability of lipid materials, enhancement of drug solubility and stability, ease of modulation of drug release, ease of scale-up, feasibility of incorporation of both hydrophilic and lipophilic drugs and occlusive moisturization, which make them very attractive carriers for delivery of bioactive compounds for treating skin ailments such as acne. In this review, the concepts of SLNs and NLCs, methods of preparation, characterization, and their application in the encapsulation of anti-acne phytochemicals will be discussed.

Transfersomes: A Promising Nanoencapsulation Technique for Transdermal Drug Delivery.

Transdermal delivery systems have gained much interest in recent years owing to their advantages compared to conventional oral and parenteral delivery systems. They are noninvasive and self-administered delivery systems that can improve patient compliance and provide a controlled release of the therapeutic agents. The greatest challenge of transdermal delivery systems is the barrier function of the skin's outermost layer. Molecules with molecular weights greater than 500 Da and ionized compounds generally do not pass through the skin. Therefore, only a limited number of drugs are capable of being administered by this route. Encapsulating the drugs in transfersomes are one of the potential approaches to overcome this problem. They have a bilayered structure that facilitates the encapsulation of lipophilic and hydrophilic, as well as amphiphilic, drug with higher permeation efficiencies compared to conventional liposomes. Transfersomes are elastic in nature, which can deform and squeeze themselves as an intact vesicle through narrow pores that are significantly smaller than its size. This review aims to describe the concept of transfersomes, the mechanism of action, different methods of preparation and characterization and factors affecting the properties of transfersomes, along with their recent applications in the transdermal administration of drugs.

Collagen biosynthesis stimulation and anti-melanogenesis of bambara groundnut (Vigna subterranea) extracts.

CONTEXT: Bambara groundnut (BG), originally from Africa, is widely distributed in Asian countries, especially in southern Thailand, and is used for food and functional foods. There is no report on the use of BG for ethnomedicine or cosmetics. OBJECTIVE: To investigate collagen biosynthesis stimulation and anti-melanogenesis of the BG extracts. MATERIALS AND METHODS: The hulls (H) and seeds (S) of BG were collected from Trang province, Thailand and extracted by Soxhlet (S) and maceration (M) using ethanol, and boiled with distilled-water (B). Total phenolic (TPC) and total flavonoid (TFC) contents were quantified. The three antioxidant and tyrosinase inhibition activities were determined by DPPH, FIC and FTC; and the modified dopachrome methods, respectively. The collagen biosynthesis and the anti-melanogenesis activities were investigated by Sirius-Red and the melanin content assay. RESULTS: The yields of BG extracts ranged from 1.72% to 9.06%. The BG-SS extract gave the highest TPC and TFC. The BG-HM extract showed the highest antioxidant activities (SC50 of 0.87 ± 0.02 mg/mL, MC50 of 1.83 ± 0.09 mg/mL and LC50 of 0.70 ± 0.06 mg/mL), tyrosinase inhibition activity (IC50 of 0.45 ± 0.23 mg/mL), and anti-melanogenesis activities (72.9 ± 0.08%), whereas the BG-SB extract exhibited the highest stimulation of collagen biosynthesis (18.04 ± 0.03%). All BG extracts at 0.1 mg/mL showed no cytotoxicity on human dermal fibroblasts. DISCUSSION: The biological activities of BG extracts might be from their phytochemicals, especially phenolic and flavonoid contents. CONCLUSION: The BG-HB and BG-HM extracts might be promising novel active sources for anti-aging and whitening cosmeceuticals.

Ex-vivo permeation study of chlorin e6-polyvinylpyrrolidone complexes through the chick chorioallantoic membrane model.

OBJECTIVE: To investigate the influence of the hydrophilic polymer, polyvinylpyrrolidone (PVP) on the ex-vivo permeability of the poorly water-soluble photosensitizer, chlorin e6 (Ce6) using the chick chorioallantoic membrane (CAM) model. METHODS: The CAM was removed from the fertilized chicken egg at embryo age of 15 days. The permeation profiles of Ce6 and PVP complexes (Ce6-PVP) at 1:0, 1:1, 1:10, 1:50 and 1:100 w/w in different pH conditions were first studied using the CAM model with Franz diffusion cell over 8 h. The solution viscosity of the formulations and apparent solubility of Ce6 were also investigated. KEY FINDINGS: The permeability of Ce6 was found to be directly proportional to the amount of PVP used and the apparent solubility of Ce6. Permeability was only marginally affected by the solution viscosity of the formulations. The permeability of Ce6 was lowered in the acidic pH. Ce6-PVP at 1:100 w/w gave the highest percentage release of Ce6 across the CAM, with 23% at pH 3 and 55% at pH 7.4, after 8 h, respectively. CONCLUSIONS: The present work suggests that PVP had served as penetration enhancer for the poorly water-soluble Ce6 and the CAM can serve as a useful biological membrane model for preclinical permeability study of biological and pharmaceutical substances. The Ce6-PVP formulation at 1:100 w/w can be applied for the further clinical investigation.

Transdermal absorption enhancement of rice bran bioactive compounds entrapped in niosomes.

Niosomes composed of Tween 61 and cholesterol at 1:1 molar ratio were entrapped with the mixture of the three semi-purified rice (Oryza sativa L., Family Gramineae) bran bioactive compounds [ferulic acid (F), γ-oryzanol (O), and phytic acid (P)] at 0.5%, 1.5%, and 1.5%, respectively, by the supercritical CO(2) technique. The transdermal absorption by vertical Franz diffusion cells of the compounds entrapped in niosomes (Nio FOP), the unentrapped compounds (Mixed FOP), the compounds incorporated in gel and cream (Gel FOP and Cream FOP), and the compounds entrapped in niosomes and incorporated in gel and cream (Gel nio and Cream nio) was investigated. At 6 h, F and P from Nio FOP gave lower cumulative amount in viable epidermis and dermis (VED) than from Mixed FOP of 1.1 and 1.6 times, respectively, while O from Nio FOP exhibited higher cumulative amount in VED than from Mixed FOP of 2.4 times. The highest cumulative amount in VED of F, O, and P were from Gel nio, Cream nio, and Mixed FOP at 1.564 ± 0.052, 15.972 ± 0.273, and 25.857 ± 0.025 ng/cm(2), respectively. Niosomes enhanced the transdermal absorption of the hydrophobic compound O, while retarded the hydrophilic compounds F and P indicating the less systemic risk of F and P than O when entrapped in niosomes. Thus, transdermal absorption of F, O, and P appeared to depend on niosomal size, lipophilicity of the bioactive compounds, and types of formulations. These preclinical results can be applied for the design of the clinical study of the developed rice bran niosomal topical products.

Anti-aging efficacy of topical formulations containing niosomes entrapped with rice bran bioactive compounds.

CONTEXT: Rice [Oryza sativa L. (Gramineae)] bran is a rich source of phytochemicals. Its oil also contains several bioactive components that exhibit antioxidative properties such as ferulic acid (F), γ-oryzanol (O), and phytic acid (P) which can be a new source of cosmetic raw materials. OBJECTIVE: To evaluate the anti-aging effects of the gel and cream containing niosomes entrapped with the rice bran bioactive compounds. MATERIALS AND METHODS: The semi-purified rice bran extracts containing F, O, and P which indicated the growth stimulation of human fibroblasts and the inhibition of MMP-2 by sulforhodamine B and gelatin zymography, respectively, were entrapped in niosomes by supercritical carbon dioxide fluid (scCO(2)) and incorporated in gel and cream formulations. The skin hydration, elasticity, thickness and roughness, and pigmentation in human volunteers after treated with these gel and creams were investigated by corneometer, cutometer, visiometer, and mexameter, respectively. RESULTS: Gel and cream containing the semi-purified rice bran extracts entrapped in niosomes gave no sign of erythema and edema detected within 72 h on the shaved rabbit skin by the closed patch test investigated by mexameter and visual observation, respectively. These formulations also demonstrated higher hydration enhancement and improvement of skin lightening, thickness, roughness, and elasticity on the skin of 30 human volunteers within the 28-day treatment not more than 9, 27, 7, 3, and 3 times, respectively. DISCUSSION AND CONCLUSIONS: The formulations containing niosomes entrapped with the rice bran bioactive compounds gave superior clinical anti-aging activity which can be applied as a novel skin product.

Antioxidant activities and skin hydration effects of rice bran bioactive compounds entrapped in niosomes.

Bioactive compounds [ferulic acid (F), gamma-oryzanol (O) and phytic acid (P)] in rice bran have been widely used as antioxidants in skin care products. However, one of the major problems of antioxidants is the deterioration of their activities during long exposure to air and light. Niosomes have been used to entrap many degradable active agents not only for stability improvement, but also for increasing skin hydration. The objective of this study was to determine antioxidant activities [by in vitro ORAC (oxygen radical absorbance capacity) and ex vivo lipid peroxidation inhibition assay] and in vivo human skin hydration effects of gel and cream containing the rice bran extracts entrapped in niosomes. Gel and cream containing the rice bran extracts entrapped in niosomes showed higher antioxidant activity (ORAC value) at 20-28 micromol of Trolox equivalents (TE) per gram of the sample than the placebo gel and cream which gave 16-18 micromolTE/g. Human sebum treated with these formulations showed more lipid peroxidation inhibition activity than with no treatment of about 1.5 times. The three different independent techniques including corneometer, vapometer and confocal Raman microspectroscopy (CRM) indicated the same trend in human skin hydration enhancement of the gel or cream formulations containing the rice bran extracts entrapped in niosomes of about 20, 3 and 30%, respectively. This study has demonstrated the antioxidant activities and skin hydration enhancement of the rice bran bioactive compounds when entrapped in niosomes and incorporated in cream formulations.

Characteristics of niosomes prepared by supercritical carbon dioxide (scCO2) fluid.

Characteristics of niosomes prepared by a novel supercritical carbon dioxide fluid (scCO(2)) technique have been investigated. Niosomes were composed of Tween61/cholesterol at 1:0, 3:1, 1:1, 1:3 and 0:1 molar ratios and entrapped with d-(+)-glucose by the scCO(2) method without and with ethanol at 5, 10 and 15% (w/w) as a co-solvent, and the conventional chloroform film method with sonication. Tween61/cholesterol at 1:1 molar ratio niosomes prepared by all methods exhibited the best physical stability. Niosomes by the scCO(2) method with 10% (w/w) ethanol gave higher trapping efficiency (12.22+/-0.26%) than those by the conventional chloroform film method with sonication (10.85+/-0.24%) and the scCO(2) method without ethanol (8.40+/-1.60%). Niosomes by the scCO(2) method with and without ethanol were large unilamellar structure under TEM with the average sizes of 271.9+/-159.6 and 202.5+/-136.7 nm, respectively, whereas those by the conventional chloroform film method with sonication were multilamellar and unilamellar structure with the average size of 58.4+/-74.6 nm. However, the dispersibility of niosomes by the conventional chloroform film method with sonication was better than that by the scCO(2) either with or without ethanol, because of smaller particle size. This present study has demonstrated the trapping efficiency enhancement of water-soluble compounds in niosomes by the scCO(2) method with 10% (w/w) of ethanol.