Cross-linked chitosan/lysozyme hydrogels with inherent antibacterial activity and tuneable drug release properties for cutaneous drug administration.

Gels with high drug release sustainability and intrinsic antibacterial properties are of high practical potential for cutaneous drug administration, particularly for wound care and skin disease treatment. This study reports the generation and characterization of gels formed by 1,5-pentanedial-mediated crosslinking between chitosan and lysozyme for cutaneous drug delivery. Structures of the gels are characterized by using scanning electron microscopy, X-ray diffractometry and Fourier-transform infrared spectroscopy. An increase in the mass percentage of lysozyme leads to an increase in the swelling ratio and erosion susceptibility of the resulting gels. The drug delivery performance of the gels can be changed simply by manipulating the chitosan/lysozyme mass-to-mass ratio, with an increase in the mass percentage of lysozyme leading to a decline in the encapsulation efficiency and drug release sustainability of the gels. Not only do all gels tested in this study show negligible toxicity in NIH/3T3 fibroblasts, they also demonstrate intrinsic antibacterial effects against both Gram-negative and Gram-positive bacteria, with the magnitude of the effect being positively related to the mass percentage of lysozyme. All these warrant the gels to be further developed as intrinsically antibacterial carriers for cutaneous drug administration.

Pulmonary embolism in menopausal hormone therapy: a population-based register study.

OBJECTIVE: Oral but not transdermal menopausal hormone therapy (MHT) increases the risk of venous thromboembolism. There is no evidence regarding the risk of the serious complication pulmonary embolism (PE). The aim was to investigate the risk of PE in women using MHT depending on administration route, type of progestin and treatment duration. METHOD: The population-based case-control study covered 1,771,253 women aged 40-69 years, during 2006-2015. Diagnoses of PE (n = 13,974) and drug dispensations were received from national validated registers. RESULTS: Current MHT users had a higher risk of PE than non-users (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.05-1.26). First ever users had the highest risk (OR 2.07, 95% CI 1.23-3.50). Transdermal administration was not associated with increased risk of PE. The OR was slightly but non-significantly higher with estrogen combined with medroxyprogesterone acetate than with norethisterone acetate. DISCUSSION: The risk of PE was significantly increased in users of oral but not transdermal MHT, with the highest risk in first ever users of oral estrogen combined with medroxyprogesterone acetate. The risk was considerably lower in women with recurrent treatment, probably because of the healthy user effect. CONCLUSION: PE was most common close to initiation of oral treatment. Transdermal MHT did not increase the risk of PE.

Laserterapia transcutânea para efeitos adversos hematopoiéticos de quimioterápicos antineoplásicos: Ensaio clínico randomizado / Terapia con láser transcutáneo para los efectos adversos hematopoyéticos de la quimioterapia antineoplásica: Ensayo clínico aleatorizado / Transcutaneous laser therapy for hematopoietic adverse effects of antineoplastic chemotherapeutics: Randomized clinical trial

Objetivo. Avaliar a eficácia dos protocolos de aplicação transcutânea do Intravenous Laser Irradiation of Blood 30' e 60', sobre os efeitos adversos no tecido hematopoiético por agentes quimioterápicos antineoplásicos endovenosos em adultos. Método. Ensaio clínico, randomizado e unicego, realizado em serviço ambulatorial de quimioterapia de hospital público do estado de São Paulo realizado de abril de 2018 a março de 2019. A amostra constituiu de 55 pacientes com tumores sólidos, a partir do segundo ciclo de tratamento com fármacos endovenosos citotóxicos para o tecido hematopoiético. O comprimento de onda utilizado foi de 660 nm, por via transcutânea, sob artéria radial. Resultado. Comparado ao tipo de hemocomponente, obtivemos, respectivamente aos protocolos do Intravenous Laser Irradiation of Blood 30' e 60': hemoglobina (85%; 86%), plaquetas (100%; 100%) e neutrófilos (95%; 92%). Conclusão. Considerou-se ambos os protocolos eficazes e, portanto, sugere-se implantá-los em unidades de quimioterapia(AU)

Objective: To evaluate the effectiveness of the protocols for transcutaneous application of the Intravenous Laser Irradiation of Blood 30' and 60', on the adverse effects on hematopoietic tissue by intravenous antineoplastic chemotherapeutic agents in adults. Method. Clinical, randomized and single-blind trial, carried out in an outpatient chemotherapy service of a public hospital in the state of São Paulo, carried out from April 2018 to March 2019. The sample consisted of 55 patients with solid tumors, from the second cycle of treatment with cytotoxic intravenous drugs for hematopoietic tissue. The wavelength used was 660 nm, transcutaneously, under the radial artery. Result. Compared to the type of blood component, we obtained, respectively from the Intravenous Laser Irradiation of Blood 30' and 60' protocols: hemoglobin (85%; 86%), platelets (100%; 100%) and neutrophils (95%; 92%). Conclusion. Both protocols were considered effective and, therefore, it is suggested to implant them in chemotherapy units.(AU)

Objetivo. Evaluar la efectividad de los protocolos de aplicación transcutánea de Irradiación Láser Intravenosa de Sangre 30' y 60', sobre los efectos adversos sobre el tejido hematopoyético por agentes quimioterápicos antineoplásicos intravenosos en adultos. Método. Ensayo clínico, aleatorizado y simple ciego, realizado en un servicio de quimioterapia ambulatoria de un hospital público del estado de São Paulo, realizado de abril de 2018 a marzo de 2019. La muestra estuvo compuesta por 55 pacientes con tumores sólidos, del segundo ciclo. del tratamiento con fármacos intravenosos citotóxicos para el tejido hematopoyético. La longitud de onda utilizada fue de 660 nm, por vía transcutánea, bajo la arteria radial. Resultado. En comparación con el tipo de componente sanguíneo, obtuvimos, respectivamente, de los protocolos de Irradiación Intravenosa con Láser de Sangre 30' y 60': hemoglobina (85%; 86%), plaquetas (100%; 100%) y neutrófilos (95%; 92%). %). Conclusión. Ambos os protocolos se consideraron efectivos, por lo que se sugiere implantarlos en las unidades de quimioterapia(AU)

Polymeric Microneedles for Transdermal Delivery of Rivastigmine: Design and Application in Skin Mimetic Model.

In the last years, microneedles (MNs) have been considered a valuable, painless, and minimally invasive approach for controlled transdermal drug delivery (TDD). Rivastigmine (RV), a drug administered to patients suffering from dementia, is currently delivered by oral or transdermal routes; however, both present limitations, mainly gastrointestinal adverse symptoms or local skin irritation and drug losses, respectively, for each route. Given this, the objective of the present work was to develop and evaluate the potential of polymeric MNs for RV transdermal delivery in a controlled manner. Polymeric MNs with two needle heights and different compositions were developed with calcein as a fluorescent model molecule. Morphology and mechanical characterisation were accessed. Skin permeation experiments showed the ability of the devices to deliver calcein and confirmed that the arrays were able to efficiently pierce the skin. To obtain a new TDD anti-dementia therapeutic solution, RV was loaded in 800 µm polymeric MNs of alginate and alginate/k-carrageenan MNs. In the presence of RV, the MN's morphology was maintained; however, the presence of RV influenced the compression force. Skin permeation studies revealed that RV-loaded MNs allowed a more efficient controlled release of the drug than the commercial patch. In vivo, skin irritation tests in rabbits revealed that the developed MNs were innocuous upon removal, in contrast with the evidence found for Exelon®, the commercial patch, which caused slight mechanical damage to the skin. The herein-produced MNs demonstrated a more controlled release of the drug, being the more suitable option for the transdermal delivery of RV.

The applications of ionic liquids in drug delivery / 药学学报

Ionic liquids (ILs) are liquid mixtures formed by anions and cations in a certain stoichiometric ratio under certain conditions. They are widely used in various fields because of their simple preparation process, low volatility, high stability, high conductivity and non-flammability. Here, we firstly introduce their formation principles, classification, and physical and chemical properties in detail. Then, we summarize their functions in pharmaceutical preparations, such as improving the solubility of insoluble drugs, enhancing the stability of drugs, and promoting the permeability of drugs, as well as their role as active pharmaceutical ingredients (API) to fabricate new drug delivery systems of API-ILs. Finally, we reviewed the applications of ILs in different administration routes, including oral, transdermal, mucosal, and injection routes, and meanwhile offer perspectives for the further use of ILs.

Topical agents: a thoughtful choice for multimodal analgesia.

For over a thousand years, various substances have been applied to the skin to treat pain. Some of these substances have active ingredients that we still use today. However, some have been discontinued due to their harmful effect, while others have been long forgotten. Recent concerns regarding the cardiovascular and renal risk from nonsteroidal anti-inflammatory drugs, and issues with opioids, have resulted in increasing demand and attention to non-systemic topical alternatives. There is increasing evidence of the efficacy and safety of topical agents in pain control. Topical analgesics are great alternatives for pain management and are an essential part of multimodal analgesia. This review aims to describe essential aspects of topical drugs that physicians should consider in their practice as part of multimodal analgesia. This review describes the mechanism of popular topical analgesics and also introduces the most recently released and experimental topical medications.

Transdermal buprenorphine for acute postoperative pain: a systematic review / Uso da buprenorfina transdérmica na dor aguda pós-operatória: revisão sistemática

Background and objectives: Postoperative pain is still a major concern in several surgical procedures. Multimodal analgesia is best for postoperative pain management; however, opioid therapy is still the main treatment for pain after surgical procedures. Transdermal buprenorphine is a partial µ-agonist opioid widely used for chronic pain syndromes, with limited evidence for acute postoperative pain. A systematic review of studies examining transdermal buprenorphine for acute pain management after surgery was conducted. Contents: Data from PubMed, Embase, The Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL via EBSCOhost, and LILACS were reviewed, including randomized clinical trials that evaluated total postoperative pain, postoperative analgesic consumption, drug-related side effects and patient satisfaction with analgesia regimen. Data from nine studies (615 patients) were included in this review. Most studies initiated transdermal buprenorphine use 6 to 48 hours before surgery, maintaining use from 1 to 28 days after the procedure. Most studies showed lower or similar postoperative pain scores, postoperative analgesic consumption and patient satisfaction comparing buprenorphine to placebo, tramadol, celecoxib, flurbiprofen and parecoxib. The incidence of side effects varied between studies, with most showing no increase in drug-related side effects with buprenorphine use, except one study, which compared buprenorphine to oral tramadol, and one to transdermal fentanyl. However, most results were derived from evidence with an overall high or unclear risk of bias. Conclusions: Although more studies are necessary, initial results show that transdermal buprenorphine seems to be an effective and safe opioid choice for management of acute postoperative pain

Justificativa e objetivos: A dor pós-operatória ainda é uma queixa importante em vários procedimentos cirúrgicos. A analgesia multimodal é a melhor conduta para a dor pós-operatória, embora a terapia com opioides ainda seja o principal tratamento para a dor após procedimentos cirúrgicos. A buprenorfina transdérmica é um opioide agonista µ amplamente prescrito nas síndromes de dor crônica, mas com limitada evidência do seu uso para dor aguda no pós-operatório. Realizamos revisão sistemática de estudos que examinaram o papel da buprenorfina transdérmica no tratamento da dor aguda pós-operatória. Conteúdo: Revisamos os dados de PubMed, Embase, Registro Central de Ensaios Controlados Cochrane (CENTRAL), CINAHL via EBSCOhost e LILACS, incluindo estudos clínicos randomizados que avaliaram a dor pós-operatória total, consumo de analgésicos pós-operatórios, efeitos colaterais relacionados a medicamentos e satisfação do paciente com esquema de analgesia. Dados de nove estudos (615 pacientes) foram incluídos nesta revisão. A maioria dos estudos iniciou o uso transdérmico de buprenorfina 6 a 48 horas antes da cirurgia, mantendo o uso de 1 a 28 dias após o procedimento. A maioria dos estudos encontrou valores semelhantes ou menores para o escore de dor pós-operatória, consumo pós-operatório de analgésicos e satisfação do paciente quando a buprenorfina foi comparada ao placebo, tramadol, celecoxibe, flurbiprofeno e parecoxibe. A incidência de efeitos colaterais oscilou nos estudos, e a maioria não mostrou aumento de efeito colateral relacionado ao uso de buprenorfina, exceto em dois estudos, um que comparou buprenorfina ao tramadol oral e outro ao fentanil transdérmico. No entanto, a maioria dos resultados foi obtida a partir de evidências com um risco geral alto ou risco de viés impreciso. Conclusões: Embora sejam necessários mais estudos, os resultados iniciais mostram que a buprenorfina transdérmica parece ser uma forma de administração segura e efetiva de opioide no tratamento da dor aguda pós-operatória

Spatially resolved diffuse imaging for high-speed depth estimation of jet injection.

We investigate the use of spatially resolved diffuse imaging to track a fluid jet delivered at high speed into skin tissue. A jet injector with a short needle to deliver drugs beneath the dermis, is modified to incorporate a laser beam into the jet, which is ejected into ex vivo porcine tissue. The diffuse light emitted from the side and top of the tissue sample is recorded using high-speed videography. Similar experiments, using a depth-controlled fiber optic source, generate a reference dataset. The side light distribution is related to source depth for the controlled-source experiments and used to track the effective source depth of the injections. Postinjection X-ray images show agreement between the jet penetration and ultimate light source depth. The surface light intensity profile is parameterized with a single parameter and an exponential function is used to relate this parameter to source depth for the controlled-source data. This empirical model is then used to estimate the effective source depth from the surface profile of the injection experiments. The depth estimates for injections into fat remain close to the side depth estimates, with a root-mean-square error of 1.1 mm, up to a source depth of 8 mm.

Medicated Foams and Film Forming Dosage Forms as Tools to Improve the Thermodynamic Activity of Drugs to be Administered Through the Skin.

Medicated foams and film forming systems are dosage forms formulated to undergo a controlled metamorphosis when applied on the skin. Indeed, due to the presence of propellant or a particular air-spray foam pump, a liquid can generate foam when applied on the stratum corneum, or a liquid or conventional dosage form can form on the skin a continuous film as a consequence of the solvent evaporation. Thanks to these controlled modifications, the drug thermodynamic activity increases favoring the skin penetration and, therefore, the bioavailability with respect to conventional semi-solid and liquid dosage forms. Furthermore, the available clinical data also evidence that these dosage forms improve the patient's compliance. The main formulative aspects of medicated foams and film forming systems are reviewed with the aim to underline the possible advantages in terms of biopharmaceutical performances and patient's adherence.

[Topical therapy of the scalp]. / Lokaltherapie der Kopfhaut.

Various hair-related diseases, systemic dermatoses as well as parasitic diseases are treated via topical application of active substances. The density of hair follicles and the consequential special conditions for diffusion require specific galenic concepts that can vary considerably depending on the respective therapeutic purpose. Both the physicochemical properties of the active ingredient and the nature of the application area must be considered when choosing an appropriate galenic base. Highly relevant here are hairiness, scarring, hyperkeratosis and exoserosis. Low-viscosity bases and foams are often preferred because of their good spreadability. Packages with nozzle tip or comb-shaped dispensers are user-friendly and can significantly enhance patient adherence to topical treatment.

Pretreatmet with 5% lidocaine patch reduces cannula-induced and propofol-induced pain: a randomized, double-blind, placebo-controlled study.

BACKGROUND: The purpose of this study was to determine the efficacy of 5% lidocaine patch in reducing propofol-induced pain and cannula-induced pain. METHODS: In a randomized, double-blind study, 126 patients were divided into one of three groups: pretreatment with a 5% lidocaine patch (Lidotop®) and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group A); pretreatment with a placebo patch and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group B); or pretreatment with a placebo patch and premixed 2 ml of 2% lidocaine (40 mg) with 1.5 mg/kg of 1% propofol (Group C) for induction of anesthesia. Pain severity was evaluated on a four-point verbal rating scale during intravenous cannulation, propofol injection, and 24 h after the operation (recall). RESULTS: Eighteen patients (47.4%) in Group A complained of cannula-induced pain compared with 35 (94.6%) in Group B and 36 (94.7%) in Group C (P < 0.001). Group A patients showed significantly lower incidence of propofol-induced pain and recall of propofol-induced pain compared with Group B (P < 0.001 and P = 0.01), whereas there was no difference compared with Group C. CONCLUSIONS: Preoperative transdermal administration of 5% lidocaine patch is an effective and simple method in reducing propofol-induced pain as well as cannula-induced pain.

Pretreatmet with 5% lidocaine patch reduces cannula-induced and propofol-induced pain: a randomized, double-blind, placebo-controlled study / 대한마취과학회지

BACKGROUND: The purpose of this study was to determine the efficacy of 5% lidocaine patch in reducing propofol-induced pain and cannula-induced pain. METHODS: In a randomized, double-blind study, 126 patients were divided into one of three groups: pretreatment with a 5% lidocaine patch (Lidotop®) and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group A); pretreatment with a placebo patch and premixed 2 ml of normal saline with 1.5 mg/kg of 1% propofol (Group B); or pretreatment with a placebo patch and premixed 2 ml of 2% lidocaine (40 mg) with 1.5 mg/kg of 1% propofol (Group C) for induction of anesthesia. Pain severity was evaluated on a four-point verbal rating scale during intravenous cannulation, propofol injection, and 24 h after the operation (recall). RESULTS: Eighteen patients (47.4%) in Group A complained of cannula-induced pain compared with 35 (94.6%) in Group B and 36 (94.7%) in Group C (P < 0.001). Group A patients showed significantly lower incidence of propofol-induced pain and recall of propofol-induced pain compared with Group B (P < 0.001 and P = 0.01), whereas there was no difference compared with Group C. CONCLUSIONS: Preoperative transdermal administration of 5% lidocaine patch is an effective and simple method in reducing propofol-induced pain as well as cannula-induced pain.

Comparison of intramuscular and subcutaneous administration of a herpes zoster live-attenuated vaccine in adults aged ≥50 years: a randomised non-inferiority clinical trial.

Zostavax(®) is a live, attenuated varicella zoster virus (VZV) vaccine developed specifically for the prevention of HZ and PHN in individuals aged ≥50 years. During the clinical development of Zostavax, which was mainly in the US, the vaccine was administrated by the subcutaneous (SC) route. In Europe, many healthcare professionals prefer administering vaccines by the intramuscular (IM) route. This was an open-label, randomised trial conducted in 354 subjects aged ≥50 years. The primary objectives were to demonstrate that IM administration is both non-inferior to SC administration in terms of 4-week post-vaccination geometric mean titres (GMTs), and elicits an acceptable geometric mean fold-rise (GMFR) of antibody titres measured by glycoprotein enzyme-linked immunosorbent assay. Pre-specified non-inferiority was set as the lower bound of the 95% confidence interval (CI) of the GMT ratio (IM/SC) being >0.67. An acceptable GMFR for the IM route was pre-specified as the lower bound of its 95% CI being >1.4. Description of the VZV immune response using the interferon-gamma enzyme-linked immunospot (IFN-γ ELISPOT) assay and of the safety were secondary objectives. Participants were randomised to IM or SC administration (1:1). The baseline demographics were comparable between groups; mean age: 62.6 years (range: 50.0-90.5). The primary immunogenicity objectives were met (per protocol analysis): GMT ratio (IM/SC): 1.05 (95% CI: 0.93-1.18); GMFR: 2.7 (2.4-3.0). VZV immune response using IFN-γ ELISPOT were comparable between groups. Frequencies of systemic adverse events were comparable between groups. Injection-site reactions were less frequent with IM than SC route: erythema (15.9% versus 52.5%), pain (25.6% versus 39.5%) and swelling (13.6% versus 37.3%), respectively. In adults aged ≥50 years, IM administration of Zostavax elicited similar immune responses to SC administration and was well tolerated, with fewer injection-site reactions than with SC administration.

Stimulating effect of essential oils from Ligusticum chuanxiong hort on HaCaT cells and skin / 第二军医大学学报

Objective To investigate the skin stimulation effect of essential oils from Ligusticum chuanxiong Hort. Methods HaCaT cells were cultured in vitro. Using MTT and ELISA methods, we examined the effect of the essential oil (different concentrations) on HaCaT cell proliferation and prostaglandin E2 (PGE2) levels in culture supernatants of HaCaT cells, and the resultswere compared with those of oleic acid, a classic permeation enhancer. The cumulative skin stimulation effect was determined by visual scoring in guinea pigs and the histological changes were determined by light microscopy. Results The HaCaT cell viabilities of the 0. 005%, 0.015%, and 0. 025% essential oil groups were 1. 79-, 1. 65-, and 1. 48-fold that of the 0. 005% oleic acid group, respectively, and there was no significant difference between the 0. 05% essential oil group and 0.005% oleic acid group. The 0. 005 %, 0.015%, 0.025%, and 0.05% essential oil influenced the supernatant PGE2 levels by (0.99±0.08)%, (1.63±0. 09) %, (0. 98±0. 09) %, and (0. 04±0. 01) %, respectively, which were all significantly lower than the influence of 0.005% oleic acid ([4. 23 + 0. 68] %, P<0. 05). Only slight erythema was observed after continuous administration the essential oil (different concentrations) for 7 days, with no edema or skin uplift, and the erythema caused by 15% essential oil was lower than that causedby5% oleic acid. Only 15% essential oil exhibited the mechanical injury of the stratum corneum. And 5 % oleic acid group showed stripped and lost stratum corneum over large areas. Conclusion Chuanxiong oil is less cytotoxic and less stimulating to the skin compared with oleic acid, and may become an excellent skin permeation enhancer.

Promoting effect of positive polarity electret combined with azone on transdermal penetration of cyclosporin A / 第二军医大学学报

Objective To study the effects of positive polarity electret combined with different concentrations of azone in promoting the transdermal delivery of cyclosporin A, so as to explore the feasibility and the rule of electret combined with chemical enhancers in promoting transdermal delivery. Methods Cyclosporin A was used as the model drug in the present study. Positive polarity electret was prepared using corona charge technique. Franz diffusion cell system and HPLC techniques were applied to investigate the roles of positive polar electret, azone of different concentrations and their combination in promoting penetration of cyclosporin A in vitro. Results Satisfactory penetration promoting effects for cyclosporin A was observed in excised skin 24 h after exposure to +500 V, +1 000 V and +2 000 V electret. Compared to the control group, 1%, 3%, and 5% azone promoted the steady-state penetration rates of cyclosporin A by 6. 72, 2. 11, and 1. 43 folds after 24 h exposure. Combination of +1 000V electret plus 1% azone showed better penetration promoting effect than other combinations, but electret with different positive charges and different concentrations of azone showed no synergistic effect in promoting cyclosporin A penetration. Conclusion Positive polarity electret has a penetration promoting effect for transdermal delivery of cyclosporin A. Positive polarity electret and azone show no synergistic effect on promoting penetration of cyclosporin A.

Microneedle technique in promoting transdermal delivery of arbutin / 第二军医大学学报

Objective: To study the promoting effects of microneedle arrays on transdermal delivery of arbutin by comparing with the effect of chemical penetration enhancer azone. Methods: The microneedles were fabricated with single-crystal Si as starting material using a series of photolithography, thin-film deposition, and reactive ion etching techniques. Franz-cells were used in the transdermal delivery experiment with human abdominal skin. The study was divided into the following 3 groups; the microneedle group (arbutin hydrogel without penetration enhancer, and the skin was treated with microneedle arrays) ; the control group (arbutin hydrogels containing 1% , 3% , and 5% azone (W/V) , and the skin received no microneedle treatment); and blank control group (arbutin hydrogel without azone, and the skin received no microneedle treatment). Arbutin levels in the receptor solution, epidermis and dermis were determined by HPLC at 1, 3 , 6 , 12, 24, 36 and 48 h. The analyses were performed with a C18 column (250 mm X 4.6 mm, 5μm), at room temperature, mobile phase methanol : 1×10-3 mol/ml HCl solution (V/V, 5 : 95), flow rate 1 ml/min, and detective wavelength 282 nm. The accumulative penetration amount (Qr), steady-state flux (J s) and the accumulative deposition amount (Qs) were calculated. Results: The microneedles could pass the human skin. The standard curve was; C=0.000 2A=0.182 9 (r=0.999 9) , 0.4-50 μg/ml. The RSD values of intraday and interday precisions were 2.4% and 2.74%, respectively; and the recovery was higher than 90%. The values of Qr, Js, and Qs in the microneedle group were significantly higher than those in the 5% azone group (P<0.01). Conclusion: Microneedles can greatly promote the skin permeability and deposition of arbutin.

Studies on transdermal delivery of sinomenine hydrochloride through mouse skin treated by microneedle arrays / 第二军医大学学报

Objective: To study the characteristics and mechanism of transdermal delivery of sinomenine hydrochloride (SH) through mouse skin treated by solid silicon microneedle arrays. Methods: The amount of SH was determined by HPLC system. Hairless rat skin was pretreated with microneedle arrays. The side-by-side diffusion cell method was used to investigate the effects of needlepoint shape, different insertion forces, retention time, and number of microneedles on transdermal SH delivery. Skin samples treated by microneedles were made into paraffin sections for histological examination and were viewed by brightfield microscopy. Results: The skin pretreated with microneedle arrays had a remarkable enhancement of SH transport compared with passive diffusion group (P<0.01); the flat tipped microneedles were more effective than the sharp tipped microneedles in enhancing the skin permeability. The accumulation of SH increased with the enhancement of insertion force; however, when the insertion force exceeded 5.0 N, the accumulation of SH no longer increased. The skin permeability was enhanced with the increase of retention time; when the retention time exceeded 1.0 min, it no longer increased SH accumulation. Although skin permeability increased with the microneedle number, there was no linear correlation was found. Histological examination showed that microneedle piercing created micro-conduits in skin. Conclusion: Microneedles can create conduits in rat skin and greatly increase the skin permeability of SH; microneedle arrays provide an efficient and promising technology for transdermal drug delivery of SH.

Preparation and in vitro percutaneous permeation profile of glycyrrhetinic acid ethosome hydrogel patch / 第二军医大学学报

Objective: To explore the preparation method of glycyrrhetinic acid ethosome (GAE) hydrogel patch and to evaluate its characteristics during in vitro transdermal drug delivery. Methods: GAE was prepared by ethanol infusion method, and its entrapment efficiency, size and surface potential were investigated. Then GAE was used to prepare the hydrogel patch. The amount of penetrated glycyrrhetinic acid was determined by HPLC on modified Franz diffusion cells, and then the in vitro transdermal drug delivery of the prepared hydrogel patch was evaluated. Results: GAE had a spherical or ellipsoidal appearance and a layered structure, with an encapsulation efficiency of (75.63 ± 1. 86)%, a particle size of (106.2 ± 20.54) nm, and a surface potential of (- 41.3 ± 2.8) mV. The percutaneous delivery rate and accumulative infiltration quantity of GAE hydrogel patch were significantly higher than those of glycyrrhetinic acid hydrogel patch. The 24 h accumulative infiltration quantity of GAE hydrogel patch was 5.55 times that of the glycyrrhetinic acid hydrogel patch (t-test, P<0.01). Conclusion: Compared with glycyrrhetinic acid, GAE can significantly improve the in vitro transdermal delivery of hydrogel patch, demonstrating that ethosome hydrogel patch might be an ideal vector for transdermal delivery of glycyrrhetinic acid.

Unusual cause of severe toxic methemoglobinemia in an infant: a case report.

Toxic methemoglobinemia is an uncommon blood disorder induced by exposure to certain oxidizing agents and drugs. In severe cases, this condition may rapidly lead to major cardiopulmonary compromise and constitutes an emergency requiring prompt recognition and early management. We report an unusual case of severe toxic methemoglobinemia following wide cutaneous application of a pomade containing benzocaine, resorcin, and oxyquinoline (Nestosyl) in an infant.

Optimized design for in vitro experiment of electret transdermal patches / 第二军医大学学报

Objective: Currently most researches concerning electret transdermal patches are performed by one-factor experimental design with relatively poor efficiency. To analyze the influencing factors in a more systematical and effective manner, we put forward an optimized design for in vitro experiment with electret transdermal patches. Methods: Due to the great number and various levels of factors impacting the charge storage stability of electrets, we combined uniform design and orthogonal design to optimize the screening for the stable transdermal patch. In the following in vitro study, we optimized the design of percutaneous experiments to screen for charge polarity and penetration enhancers using a two-factor experimental design. And using an orthogonal experimental design, we further studied the influence of different levels of main drug, surface potential and penetration enhancer on transdermal absorption. Conclusion: The present design, taking into consideration of various factors and using multi-factor experimental design, can more effectively analyze data, reduce workload, and is feasible.