Transdermal Absorption Research Articles

Transdermal Absorption Enhancement of Cosmetic Ingredients into the Stratum Corneum by Multi Spike Moist Pulse

皮膚に有用な美容成分の浸透を電気刺激で促進させる手法は種々しられている。われわれは，美容成分の角層への浸透を高める電気浸透波形6種類の角層への浸透量の違いについてアニオン性を有するリン酸アスコルビルMgとカチオン性傾向のナイアシンアミドの2種類の美容成分を用いて比較検討した。その結果，このたび開発したエレクトロポレーション要素と高周波要素を併せもつ複合浸透波形がきわめて浸透量が多いことが示された。（1）イオントフォレーシスはコントロールに比べ浸透量が多い傾向であり従来の報告と一致するものであったが有意差は見られなかった。また高周波（RF）もコントロールに比べ浸透量が多い傾向ではあったもののリン酸アスコルビルMgでは有意差は見られなかった。（2）複合浸透波形と同一の出力電力である矩形波と比較したところ，複合浸透波形は矩形波に比べ有意に浸透量が多いことから複数の要素を併せもつ複合浸透波形が角層への浸透を顕著に促進することが明らかになった。

415 Efficacy of 2% crisaborole ointment in 49 patients of atopic dermatitis with chronic hyperplasia lesions: a real-world study

Abstract Asian Atopic dermatitis (AD) presents as a mixed phenotype between the European American (EA) AD and psoriasis phenotypes, with highly atypical features for AD, including clearer demarcation of lesions, with more prominent scaling, lichenification, parakeratosis, hyperplasia and a unique cytokine profile with coactivation of the TH2 and TH17 axes. The cutaneous immune dysregulation in Chinese patients with AD usually exhibit remarkable increase in epidermal hyperplasia and parakeratosis, frequently observed in areas such as the hands, feet, knees and elbows. Currently, the response of chronic hyperplastic lesions to various conventional treatment modalities, including topical corticosteroids and topical calcineurin inhibitors, is not optimistic and often accompanied by various complications. As a Phosphodiesterase 4 (PDE4) inhibitor, crisaborole broadly inhibits inflammatory signaling pathways, and has demonstrated definite efficacy in AD partly due to its smaller molecular weight and higher transdermal absorption efficiency. This study aims to find the clinical efficacy of 2% crisaborole ointment monotherapy for chronic hyperplastic lesions of AD in real-world research in China. We retrospectively enrolled 49 patients with AD aged 12 years or older with chronic hyperplastic lesions and an Investigator’s Static Global Assessment (ISGA) score of mild or moderate. The patients were administered with 2% crisaborole ointment for twice-daily application until the complete clearance of lesion. The efficacy endpoints comprised the onset time of pruritus and lesion remission, and the time of complete lesion clearance. A 1-grade or more improvement of the VAS scores from baseline was defined as the pruritus remission. An improvement of 1 point or more of the ISGA scores was indicative of improved skin lesions. The ISGA score of 0 (clear) or 1 (almost clear) with a ≥2-grade improvement from baseline indicated complete remission of skin lesions. After subgrouping the patients by age and AD duration, we further compared differences in efficacy endpoints to explore potential influencing factors on the effectiveness of crisaborole. Two percent crisaborole ointment showed good efficacy for treating chronic hyperplasia lesions in Asian patients with AD, with minor irritation, early remission of pruritus [7.0 ( 3.0, 10.0) days] and lesions [7.0 (5.0, 10.0) days]. The median time for complete lesion clearance was 30 days. Two percent crisaborole ointment showed different efficacy in the different age. The onset of pruritus remission appeared to be more rapid in the elderly [2.0 (1.0, 10.0)] compared with the adolescents [4.0 (2.3, 6.5)] and the adults [7.0 (3.5, 10.0)], but with no statistically significant difference (P = 0.072). The adolescents had an earlier onset of lesion remission by approximately 3 days compared with the adults and the elderly (P = 0.044). Although the onset of pruritus remission for the adolescents and the adults was similar to their onset of lesion remission, the elderly seemed to experience significantly earlier pruritus remission compared with their lesion remission onset. There was no statistical difference in complete lesion clearance time among different age groups (P = 0.019). Commonly seen in Asian patients with AD, chronic hyperplasia lesions generally do not respond well to other topical medications. Two percent crisaborole ointment monotherapy is an effective treatment for chronic hyperplasia lesions in patients with AD of all age groups, and onset of pruritus and lesion remission is different in the different age group.

Qualitative analysis on the transdermal absorption from the dichloromethane extract of the Sambucus adnata wall. based on UPLC-Q-Exactive Orbitrap/MS

Sambucus adnata Wall.(SAW) has been used to treat osteoarthritis by the Yi nationality in China. The present study established an overall identification strategy based on ultra-high performance liquid chromatography-tandem Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) method to characterize the multiple chemical constituents of SAW before and after percutaneous penetration. Nineteen compounds, including triterpenoids, fatty acids, lignans, flavonoid, and amide, were tentatively identified in the dichloromethane extract of SAW, while fourteen ingredients penetrated the skin. Among them, eleven components were reported for the first time in SAW.

Effect of microneedle roller on promoting transdermal absorption of crossbow-medicine liquid via transdermal administration of Traditional Chinese Medicine and the safety of crossbow-medicine needle therapy: An experimental study

Ethnopharmacology relevanceCrossbow-medicine needle therapy (microneedle roller combined with crossbow-medicine) is one of the external treatment methods of Miao Medicine in China. It is a way of combining acupuncture with Chinese herbal medicine, which is widely used in clinical treatment of pain. Aim of the studyTo observe the transdermal absorption promoting effect of microneedle roller via transdermal administration, and to discuss the transdermal absorption characteristics and the safety of crossbow-medicine needle therapy. MethodsBased on the determination of the content of the main components of crossbow-medicine prescription in our previous research, the present experiment was conducted in-vitro and in-vivo experiments and the skin of rats was used as the penetration barrier. For in-vitro experiment, the modified Franz diffusion cell method was used to determine the transdermal absorption rate and 24h cumulative transdermal absorption amount of the active ingredients of crossbow-medicine liquid. For in-vivo experiment, tissue homogenization was applied to compare the skin retention amount and plasma concentration of crossbow-medicine liquid absorbed at different time points via the aforementioned two modes of administration. Furthermore, the effect of crossbow-medicine needle on the morphological structure of rat skin stratum corneum was detected by hematoxylin-eosin (HE) staining. The safety of crossbow-medicine needle therapy was evaluated according to the scoring criteria of the skin irritation test. Results1. In-vitro experiment: In the microneedle-roller group and crossbow-medicine liquid application group, the effect of transdermal delivery was identified in all the four ingredients of anabasine, chlorogenic acid, mesaconitine and hypaconitine. The 24h cumulative transdermal absorption amount and transdermal absorption rate of each ingredient in microneedle-roller group were significantly higher than those in crossbow-medicine liquid application group (all P < 0.05). 2. In-vivo experiment: Both microneedle-roller and crossbow-medicine liquid application could promote the transdermal absorption of the active ingredients of the drug in the skin and retain in the skin structure. After 8h of administration, the total retention amount of anabasine, chlorogenic acid, mesaconitine and hypaconitine in the skin of rats in the former group was significantly higher than that in the latter group (all P < 0.05). 3. HE staining: In the blank group, the stratum corneum showed an evenly zonal distribution on the active epidermis, and had a close connection with the epidermis, without exfoliation or cell dissociation of the stratum corneum. The crossbow-medicine liquid group had a relatively complete stratum corneum, with a small proportion of exfoliation or cell dissociation, loose arrangement and loose connection with the epidermis. In the microneedle-roller group, the skin had pore channels, and the stratum corneum was loose and exfoliated, which showed zonal distribution in a free state and a high degree of separation. The crossbow-medicine needle group had loose the stratum corneum, broken and exfoliated, which was separated from the active epidermis and showed zonal distribution in a free state. 4.Safety: No obvious erythema, edema and skin protuberance were observed in the skin of rats treated with microneedle roller, crossbow-medicine liquid and crossbow-medicine needle. Additionally, the skin irritative response score was 0. ConclusionMicroneedle roller can promote the transdermal absorption of crossbow-medicine liquid, and crossbow-medicine needle therapy has good safety.

A novel deformable liposomal hydrogel loaded with a SREBP-1-inhibiting polypeptide for reducing sebum synthesis in golden hamster model

Excessive sebum is the major factor involved in the pathophysiology of seborrheic diseases. Chemical medicines can result in mild to severe side effects. Polypeptides with much less side effects make them ideal for reducing sebum synthesis. Sterol regulatory element-binding proteins-1 (SREBP-1) is necessary for the biosynthesis of sterols. A SREBP-1-inhibiting polypeptide (SREi), which competitively inhibits the ubiquitination of Insig-1 so as to suppress the activation of SREBP-1 was selected as an active ingredient and formulated into skin topical preparations. The SREi anionic deformable liposomes contained sodium deoxycholate (SDCh) at the concentration of 4.4 mg/mL (SREi-ADL3) and SREi-ADL3 in 0.3% (w/v) carbomer hydrogel (SREi-ADL3-GEL) were prepared and characterized. The SREi-ADL3 presented a high entrapment efficiency of 92.62 ± 6.32%, a particle size of 99.54 ± 7.56 nm and a surface charge of -19.18 ± 0.45 mV. SREi-ADL3-GEL exhibited a sustained release behavior, a higher stability, a much more cellular uptake ability and transdermal absorption. In vivo golden hamster model confirmed that SREi-ADL3-GEL presented the strongest inhibitory effect on sebaceous gland growth and sebum synthesis by down-regulating the mRNA and protein expression of SREBP-1, fatty acid synthase (FAS) and acetyl–coenzyme A carboxylase 1 (ACC1). As confirmed by histological analysis, only a small amount of sebaceous gland lobes with the lightest staining intensity and the smallest dyeing area could be observed in the SREi-ADL3-GEL group. Taken together, SREi-ADL3-GEL displayed potential applications in sebum excessive production related diseases.

ВЛАГОЧУВСТВИТЕЛЬНЫЕ IN SITU СИСТЕМЫ В КОМПЛЕКСНОЙ ТЕРАПИИ АТОПИЧЕСКОГО ДЕРМАТИТА

Self-emulsifying drug delivery systems (SEDDS) are modern forms for drug agent delivery with improved biopharmaceutical characteristics. By their formation mechanism they belong to the group of in situ systems - forms formed at the application site, under the influence of specific physiological or pathological factors. Dermatological SEDDS for external use that form an emulsion at the absorption site upon contact with water are characterized by a number of advantages, both in terms of use and technology. Moisture-sensitive SEDDS are compositions of oil, surfactant, emollients and co-surfactants. Emulsification occurs with minimal mechanical action, and the emulsion formed provides effective transdermal absorption of the active ingredients, soothing, moisturizing, and protective effects on the skin. All these advantages can be effectively applied in local symptomatic treatment of atopic dermatitis. Topical SEDDS are currently known to be developed for the treatment of melanoma, viral and fungal diseases, protection against ultraviolet radiation. Atopic dermatitis (AD) is a chronic dermatological disease accompanied by itching, burning, dry and flaky skin, reduced protective function of the epidermis, susceptibility to fungal and bacterial infections. Using alkaline skin care products for patients with AD negatively affects the pH of the skin and affects it accordingly. In addition, the using of soaps causes thinning of the skin in both normal and atopic skin, which can aggravate the course of the disease. Therefore, the use of moisture-activated SEDDS in the complex external treatment of AD is reasonable both as agents for daily skin care, maintenance of its basic functions, and as drugs for transdermal delivery of active ingredients.

Anti-Photoaging Effects of Nanocomposites of Amphiphilic Chitosan/18β-Glycyrrhetinic Acid.

Improving the transdermal absorption of weakly soluble drugs for topical use can help to prevent and treat skin photoaging. Nanocrystals of 18β-glycyrrhetinic acid (i.e., NGAs) prepared by high-pressure homogenization and amphiphilic chitosan (ACS) were used to form ANGA composites by electrostatic adsorption, and the optimal ratio of NGA to ACS was 10:1. Dynamic light scattering analysis and zeta potential analysis were used to evaluate the nanocomposites' suspension, and the results showed that mean particle size was 318.8 ± 5.4 nm and the zeta potential was 30.88 ± 1.4 mV after autoclaving (121 °C, 30 min). The results of CCK-8 showed that the half-maximal inhibitory concentration (IC50) of ANGAs (71.9 μg/mL) was higher than that of NGAs (51.6 μg/mL), indicating that the cytotoxicity of ANGAs was weaker than that of NGAs at 24 h. After the composite had been prepared as a hydrogel, the vertical diffusion (Franz) cells were used to investigate skin permeability in vitro, and it was shown that the cumulative permeability of the ANGA hydrogel increased from 56.5 ± 1.4% to 75.3 ± 1.8%. The efficacy of the ANGA hydrogel against skin photoaging was studied by constructing a photoaging animal model under ultraviolet (UV) irradiation and staining. The ANGA hydrogel improved the photoaging characteristics of UV-induced mouse skin significantly, improved structural changes (e.g., breakage and clumping of collagen and elastic fibers in the dermis) significantly, and improved skin elasticity, while it inhibited the abnormal expression of matrix metalloproteinase (MMP)-1 and MMP-3 significantly, thereby reducing the damage caused by UV irradiation to the collagen-fiber structure. These results indicated that the NGAs could enhance the local penetration of GA into the skin and significantly improve the photoaging of mouse skin. The ANGA hydrogel could be used to counteract skin photoaging.

Toxic Fumes Exposure–More than Just an Airway Concern – RETRACTED

Introduction:Exposure to toxic fumes from an industrial chemical fire may not only lead to airway burns and inhalational injury but also toxic exposure via the transdermal route.Method:A 45-year-old gentleman presented with dyspnea two hours after a ten-minute exposure to toxic fumes while fighting an industrial chemical fire without personal protective equipment. He reported voice hoarseness and chest tightness. Nasoendoscopy demonstrated paranasal sinus soot and significant upper airway edema. Awake fiber-optic intubation was performed for prophylactic airway protection in the Burns ICU but bronchoscopy did not reveal any inhalational burns.However, the patient developed worsening lactic acidosis (serum lactate 2.8mmol/L to 8.1mmol/L with pH 7.28) within 12 hours post-exposure. Carboxyhemoglobin was 0.9%. Toxicology was consulted for suspicions of transdermal HAZMAT contamination, in particular cyanide given the profound lactic acidosis. The patient was given two doses of hydroxocobalamin and brought to the Hospital Decontamination Unit for de-gowning and thorough wash-down. The chemical scan meter showed high levels (352IU) of an unknown chemical on his skin pre-decontamination, which could not be detected post-decontamination. Lactate improved to 5.0mmol/L within two hours post-decontamination while acidosis resolved at eight hours post-decontamination. The patient was extubated and discharged without sequelae.Results:To our knowledge, no other human cases of transdermal cyanide poisoning have been reported. Cyanide interferes with mitochondrial oxidative phosphorylation pathways to cause toxicity and death if untreated. However, its effects via transdermal exposure are often delayed compared to exposure via more conventional inhalational routes. This makes recognition difficult and compounds the challenge of long turnaround time for blood cyanide tests. Increased transdermal absorption is possible through intact skin if moistened by sweat.Conclusion:The potential for transdermal HAZMAT absorption from exposure to toxic fumes is underrecognized. It is crucial to maintain vigilance given the challenges in diagnosing transdermal cyanide toxicity and importance of initiating treatment early.

Design and Development of Functionalized Single-walled Carbon Nanotube-ethosomes for Transdermal Delivery of Ketoprofen.

The purpose of this study was to combine carbon nanotube with ethosomes in order to obtain hybrid nanocarriers for transdermal delivery of ketoprofen (KP). KP-loaded functionalized single-walled carbon nanotube (f-SWCNTs) composite ethosomes (f-SWCNTs-KP-ES) were designed and were verified by a series of characterizations. The particle size of the preparation is less than 400 nm. DSC and XRD experiments showed that KP existed in an amorphous state after it was adsorbed and loaded on f-SWCNTs. TEM experiments showed that the structure of SWCNTs remained intact after oxidation and modification by PEI. FTIR results showed that PEI were successfully modified on the surface of SWCNT-COOH, and KP was successfully loaded on f-SWCNTs. In vitro release characteristics showed that the preparation had sustained release behavior and conformed to the first-order kinetic equation model. In addition, f-SWCNTs-KP-ES gel were prepared and in vitro skin permeation and in vivo pharmacokinetics were studied. The results showed that f-SWCNTs-KP-ES gel could enhance the skin permeation rate of KP and increase the drug retention of drugs in the skin. The characterization results consistently showed f-SWCNTs is a promising drug carrier. The hybrid nanocarrier prepared by the combination of f-SWCNTs and ethosomes can enhance the transdermal absorption of drugs and improve the bioavailability of drugs, which has a certain significance for the development of advanced hybrid nano-preparations.

Influence of Types of Media and Modes of Therapeutic Ultrasound on drug absorption in phonophoresis: A Comparative Experimental study on rabbits

Although non-invasive transdermal application of various pharmaco-therapeutic drugs via phonophoresis (PH) is widely used in physical therapy, the influence of the type of medium in which the drug is prepared and mode of ultrasound on drug absorption is hardly explored. Hence, the same formed the aim of this study. In this study, serum concentration of diclofenac sodium (DS) was quantified and compared between gel and cream medium, using continuous mode (CTUS) and pulsed (PTUS) mode of Therapeutic Ultrasound (TUS) respectively. Study was conducted on eight healthy adult rabbits with 1% DS in gel and cream as topical application (TA) and PH using TUS of 1 MHz with 1 W/cm2 in CTUS and 20% PTUS respectively for 8 minutes during each session. Blood samples were analysed for drug concentration in serum by High performance liquid chromatography (HPLC) assay. Comparison of DS concentration in plasma showed a significant difference with cream than gel medium in both CTUS (p=&lt;.001) and PTUS (p=.005) mode. For the modes of TUS, PTUS showed significance against TA in both gel (p= &lt;.001) and cream (p=.001) and with CTUS better with TA in cream (p = 0.003) medium. The transdermal drug absorption was significantly higher in the cream than gel medium, having similar results between continuous and pulsed TUS. PH also confirmed significantly higher drug absorption than TA in both media and modes of TUS.

A Conformable Ultrasound Patch for Cavitation-Enhanced Transdermal Cosmeceutical Delivery.

Increased consumer interest in healthy-looking skin demands a safe and effective method to increase transdermal absorption of innovative therapeutic cosmeceuticals. However, permeation of small-molecule drugs is limited by the innate barrier function of the stratum corneum. Here, a conformable ultrasound patch (cUSP) that enhances transdermal transport of niacinamide by inducing intermediate-frequency sonophoresis in the fluid coupling medium between the patch and the skin is reported. The cUSP consists of piezoelectric transducers embedded in a soft elastomer to create localized cavitation pockets (0.8 cm2 , 1mm deep) over larger areas of conformal contact (20 cm2 ). Multiphysics simulation models, acoustic spectrum analysis, and high-speed videography are used to characterize transducer deflection, acoustic pressure fields, and resulting cavitation bubble dynamics in the coupling medium. The final system demonstrates a 26.2-fold enhancement in niacinamide transport in a porcine model in vitro with a 10 min ultrasound application, demonstrating the suitability of the device for short-exposure, large-area application of sonophoresis for patients and consumers suffering from skin conditions and premature skin aging.

Immobilized Keratin HPLC Stationary Phase-A Forgotten Model of Transdermal Absorption: To What Molecular and Biological Properties Is It Relevant?

Chromatographic retention data collected on immobilized keratin (KER) or immobilized artificial membrane (IAM) stationary phases were used to predict skin permeability coefficient (log Kp) and bioconcentration factor (log BCF) of structurally unrelated compounds. Models of both properties contained, apart from chromatographic descriptors, calculated physico-chemical parameters. The log Kp model, containing keratin-based retention factor, has slightly better statistical parameters and is in a better agreement with experimental log Kp data than the model derived from IAM chromatography; both models are applicable primarily to non-ionized compounds.Based on the multiple linear regression (MLR) analyses conducted in this study, it was concluded that immobilized keratin chromatographic support is a moderately useful tool for skin permeability assessment.However, chromatography on immobilized keratin may also be of use for a different purpose-in studies of compounds' bioconcentration in aquatic organisms.

Preparation, Characterization and ex vivo Skin Permeability Evaluation of Type I Collagen-Loaded Liposomes.

In the present study, we prepared collagen liposomes with the addition of polyol, which is expected to not only increase the solubility of collagen but also improve skin penetration. Collagen liposomes were prepared by the film dispersion method, and their characteristics, integrity and biosafety were evaluated by Fourier transform infrared spectroscopy (FTIR), UV-VIS spectroscopy, polyacrylamide gel electrophoresis (SDS-PAGE), dynamic light scattering (DLS) and transmission electron microscope (TEM). The transdermal absorption of collagen and collagen liposomes were tested by an ex vivo horizontal Valia-Chien diffusion cell system. We first demonstrated that collagen extracted from bovine Achilles tendon was type I collagen. The results of DLS measurement and TEM observation showed that the collagen liposomes were spherical in shape with average diameter (75.34±0.93 nm) and maintained high stability at low temperature (4°C) for at least 42 days without toxicity. The encapsulation rate of collagen liposomes was 57.80 ± 0.51%, and SDS-PAGE analysis showed that collagen was intact in liposomes. Finally, permeability studies indicated that the collagen-loaded liposomes more easily penetrated the skin compared to collagen itself. This study proposed a new method to improve the bioavailability and permeability of bovine type I collagen, which improves the applicability of collagen in biomedicine, cosmeceuticals and pharmaceutical industries.

Evaluating Neutral PFAS for Potential Dermal Absorption from the Gas Phase.

Exposures to per- and polyfluoroalkyl substances (PFAS) are of increasing concern. Assessments typically focus only on ingestion and inhalation exposure due to a lack of generally accepted approaches for estimating dermal absorption. Prior work indicates limited dermal absorption of ionic PFAS, but absorption of neutral PFAS has not been examined from the liquid vehicle or from vapor. Partitioning of semivolatile organic compounds from the gas phase to the skin surface (i.e., stratum corneum) is well known, but the potential for partitioning of neutral PFAS from the gas phase to the stratum corneum has yet to be estimated. The SPARC-estimated physicochemical properties were used to calculate transdermal permeability coefficients (kp_g) and dermal-to-inhalation (D/I) exposure ratios for two groups of neutral PFAS, including those on a U.S. Environmental Protection Agency PFAS list. 11 neutral PFAS gave calculated D/I ratios >5, indicating that direct transdermal absorption may be an important exposure pathway compared to inhalation. Data on consumer products or indoor air is needed for the 11 neutral PFAS, followed by possible biomonitoring to experimentally verify dermal absorption from air. Additional PFAS should be estimated by the protocol used here as they are identified in commercial products.

Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

Skin drug delivery using lipid vesicles: A starting guideline for their development.

Lipid vesicles can provide a cost-effective enhancement of skin drug absorption when vesicle production process is optimised. It is an important challenge to design the ideal vesicle, since their properties and features are related, as changes in one affect the others. Here, we review the main components, preparation and characterization methods commonly used, and the key properties that lead to highly efficient vesicles for transdermal drug delivery purposes. We stand by size, deformability degree and drug loading, as the most important vesicle features that determine the further transdermal drug absorption. The interest in this technology is increasing, as demonstrated by the exponential growth of publications on the topic. Although long-term preservation and scalability issues have limited the commercialization of lipid vesicle products, freeze-drying and modern escalation methods overcome these difficulties, thus predicting a higher use of these technologies in the market and clinical practice.

Clinical practice Guidelines for 5-Aminolevulinic acid photodynamic therapy for acne vulgaris in China.

A variety of evidence suggest that 5-Aminolevulinic acid-based photodynamic therapy (ALA-PDT) is clinically effective in management of acne vulgaris. Several clinical guidelines for acne recommend PDT as an alternative treatment modality for severe acne. However, there is a lack of detailed clinical guideline for PDT in acne treatment. To propose up-to-date, evidence-based and practical recommendations on application of ALA-PDT for acne vulgaris, dermatologists and PDT experts from the Photodynamic Therapy Research Center of the CMA and Photodynamic Therapy Rehabilitation Training Center of CARD achieved consensus and guidelines based on careful evaluation of published literature, expert opinions and experience. ALA-PDT plays a therapeutic role in all four major pathogenesis of acne, and is suitable for moderate to severe acne and scar-prone acne, especially for patients who cannot tolerate or refused systemic antibiotics and isotretinoin. The efficacy and adverse reactions of ALA-PDT are closely related to therapeutic parameters including ALA concentration, incubation time, light source and dosage. Proper pretreatment helps to improve transdermal absorption of ALA and enhances its efficacy. We reviewed and proposed recommended protocols for four PDT procedures including conventional PDT (C-PDT), modified painless PDT (M-PDT), intense pulsed light PDT (IPL-PDT) and daylight PDT (DL-PDT). M-PDT with lower ALA concentration (3-5%), shorter incubation time (30 mins), and lower dose but prolonged illumination (630nm, 40-60 mW/cm2, 150 J/cm2) can improve lesions of moderate to severe acne vulgaris effectively with minimal pain and easier manipulation, and thus was recommended by Chinese dermatologists. Lastly, management of adverse reactions were addressed.

Hyaluronidase Promote Transdermal Diffusion of Small Sized Curcumin Nanocrystal by Dissolving Microneedles Delivery.

Hyaluronidase is clinically used in treating many skin diseases due to its good permeability-promoting effect, which may motivate the diffusion and absorption of drugs. To verify the penetration osmotic effect of hyaluronidase in microneedles, 55 nm-size curcumin nanocrystals were fabricated and loaded into microneedles containing hyaluronidase in the tip. Microneedles with bullet shape and backing layer of 20% PVA + 20% PVP K30 (w/v) showed excellent performance. The microneedles were able to pierce the skin effectively with a skin insert rate of 90% and demonstrated good mechanical strength. In the in vitro permeation assay, with the increase of hyaluronidase concentration at the tip of the needle, the cumulative release of curcumin increased, as well as the skin retention decreased. In addition, compared with the microneedles without hyaluronidase, the microneedles containing hyaluronidase in the tip exhibited a larger drug diffusion area and deeper diffusion depth. In conclusion, hyaluronidase could effectively promote the transdermal diffusion and absorption of the drug.

A theoretical investigation on the synergetic effect of hydrogen-bonding interactions and thermodynamic property in the 1: 2 (azacyclopentane-2-one: N-methylolacetamide) ternary complex.

Using chemical penetration enhancers to improve the penetration effect is one kind of important strategies in transdermal drug delivery system. Azone is a widely used transdermal absorption enhancer for transdermal drug delivery. To shed light on the permeation-promoting mechanism of azone, we selected ternary systems formed by azacyclopentane-2-one and N-methylolacetamide (1: 2) and explored the synergetic effect of hydrogen-bonding interactions among them and their thermodynamic properties. The findings indicate that the synergetic effects can enhance the ability of azone to change the original conformation of ceramides and even break the original hydrogen bonds, which is more beneficial for azone to destroy the 3D network structure of ceramides. When azone interacts with ceramide, the order of action tends to interact with one molecule of ceramide first and then with another molecule of ceramide. The synergetic effects of hydrogen-bonding interactions in ternary systems were computed at the B3LYP/6-311 + + G** and MP2(full)/6-311 + + G** levels. Thermodynamic parameters for two ternary-complex routes were worked out at the B3LYP/aug-cc-pVDZ level. The shift of the electron density occurring simultaneously with trimer formation was analyzed at the MP2(full)/6-311 + + G** level. The above calculations were carried out using the Gaussian 03 program packages. Atoms in molecules (AIM) method and the AIMPAC program showed the topological charge density at the MP2(full)/6-311 + + G** level. The synergetic effects of hydrogen-bonding interactions and thermodynamic property in the 1: 2 (azacyclopentane-2-one: N-methylolacetamide) ternary systems were investigated using the B3LYP and MP2(full) methods.

Preparation of tanshinone IIA self-soluble microneedles and its inhibition on proliferation of human skin fibroblasts

ObjectiveHypertrophic scars (HS) are a variety of skin tissue fibrosis disease that occurs in human skin, the effective therapeutic method of which is still inaccessible up to now. As a bioactive constituent of a well-known medical plant, Salvia miltiorrhiza (Danshen in Chinese), tanshinone IIA (TSA) is reported to inhibit cell proliferation in HS. Therefore, the aim of this study was to prepare TSA self-soluble microneedles to strengthen its dermal retention and break through the difficulty of significantly thickening epidermal connective tissue and stratum corneum at the HS site. The possible mechanism of action in suppressing HS was studied using human skin fibroblasts (HSF). MethodsTanshinone IIA self-dissolving microneedles (TSA-MN) was prepared using a negative mold casting method. The prescription process of microneedle was optimized by Box-Behnken effect surface method. Different media were selected to investigate the ability of transdermal absorption and in vitro release. Furthermore, according to Cell Counting Kit-8 (CCK8) method as well as the Western blot method, the effect of TSA-MN on the biological characteristics of HSF was investigated. ResultsWith remarkable slow release effect and dermal retention, the release and transdermal properties of TSA-MN in vitro were better than both TSA and ordinary dosage forms. Its effect of HSF confirmed the essential decrease in cell motility during cell proliferation and cell migration in vitro, which plays a significant role in down-regulating the secretion of transforming growth factor-β1 (TGF-β1) in HSF and increasing the expression level of Smad7. ConclusionThe prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars, with a stable dermal retention effect after process optimization.