A randomized clinical trial of transdermal (gel) versus oral estrogen for endometrial preparation in frozen embryo transfer cycle

SUMMARY OBJECTIVE: The aim of this study was to compare endometrial thickness with the use of transdermal estrogen (gel) versus oral estrogen (pills) for endometrial preparation in the frozen embryo transfer cycle and serum estrogen concentrations during the preparation cycle, side effects, and chemical and clinical pregnancy rates. METHODS: This was a prospective, randomized controlled trial of women undergoing endometrial preparation for cryopreserved blastocyst transfer. A total of 88 women were randomized, of which 82 completed the study protocol. Of this group, 44 received 6 mg/day of estradiol valerate orally (pills group) and 38 received 4.5 mg/day of estradiol hemihydrate transdermally (gel group). Endometrial thickness was measured using transvaginal ultrasound between the 7 and 10th day of the cycle. Serum estradiol concentrations were measured on the day of initiating the cycle, on control transvaginal ultrasounds, and on the day of embryo transfer. Side effects were documented at each study visit. p<0.05 were adopted as statistically significant. The groups were compared using Student's t-test for continuous variables and chi-square or Fisher's exact test for categorical variables. RESULTS: There were no significant group differences (p>0.05) in endometrial thickness, biochemical and clinical pregnancy rates, miscarriage rate, blood estradiol concentrations, duration of estradiol administration, or cycle cancellation rates. CONCLUSION: Endometrial preparation with transdermal estrogen yielded similar reproductive outcomes to oral estrogen with fewer side effects.

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)

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.

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

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.

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.

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.

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.

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.

Study on microneedle technique in enhancement of transdermal nanoparticle delivery / 第二军医大学学报

Objective: To investigate the microneedle technique in enhancement of transdermal nanoparticle delivery and the distribution of poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles in the skin and the transdermal microconduits. Methods: Double fluorescent PLGA nanoparticles were used to show the transdermal transport process. Franz diffusion cell was used for the transdermal study. The nanoparticle suspension was added to the donor chamber. The hairless mouse skin in the microneedle group was treated by microneedle technique and that in the control group was not treated. Penetration of nanoparticles was visualized by confocal laser scanning microscopy (CLSM). Distribution of nanoparticle diameter was quantified by HPLC. Results: The CLSM images revealed that the nanoparticles were delivered into the microconduits created by microneedles and entered the epidermis and the dermis. The quantitative results showed that no nanoparticles reached the receptor compartment 48 h after addition of the nanoparticles in both groups. In microneedle group the nanoparticle amount was 125.99 μg/cm2 in the epidermis and 55.31 μg/cm2 in the dermis, with the total amount in the skin being 181.30 μg/cm2; in the the control group, the nanoparticle amount was 42.15 μg/cm2 in the epidermis and 32.76 μg/cm2 in the dermis, with the total amount in the skin being 74.91 μg/cm2. Microneedle technique significantly increased the amount of nanoparticles entering the skin (P<0.01), and the amount in the epidermis was significantly more than that in the dermis (P<0.01). Conclusion: Our results suggest that microneedles can enhance the intradermal PLGA nanoparticle delivery, and the nanoparticles deposit in the skin to achieve sustainable drug release, which is beneficial for topical drug administration.

Enhancing effect of negative electret on percutaneous drug absorption of meloxicam patch in SD rats / 第二军医大学学报

Objective: To determine meloxicam concentrations in both plasma and extract solution of tested-skin in SD rats and the fluorescence intensity, location of fluorescein sodium salt (NaFI) in striped rat skin within 4 h after transdermal administration, so as to investigate the enhancing effect of negative electret on percutaneous absorption of meloxicam and percutaneous absorption route of NaFI. Methods: Pharmaceutical method and grid-controlled constant corona charge technique were used to prepare electret meloxicam patch. High performance liquid chromatography (HPLC) method was employed to determine meloxicam concentration after transdermal administration. NaFI was used as probe to determine the localization and percutaneous absorption route of NaFI by using laser scanning confocal microscopy (LSCM). Results: (DNegative electret and its polypropylene(PP) electret meloxicam patch exhibited a good charge storage stability. (2)The results of HPLC demonstrated that electret had a remarkable enhancing effect on percutaneous absorption of meloxicam after application for 1-4 h. (3) LSCM further proved the enhancing effect of negative electret on percutaneous absorption of small molecules. We also found that the stratum corneum and the hair follicle areas were the two main pathways for the enhancing effect of the electret. Conclusion: Negative electret can be used as an enhancer for transdermal permeation of meloxicam.

Enhancing effects of electret on transdermal delivery of lidocaine patches in vitro / 第二军医大学学报

Objective: To study the enhancing effects of electret on transdermal delivery of lidocaine patches in vitro. Methods: In vitro rat skin permeation experiment was carried out with lidocaine patches, lidocaine paches with azone, positive/negative electret lidocaine patches, and positive/negative electret lidocaine patches with azone by using Franz diffusion cells. The accumulated lidocaine concentrations in rat skin treated with each kind of patches were examined by HPLC to investigate the influence of electret on transdermal delivery of lidocaine. Results: (1) The enhancement rates of 1%, 3% and 5% azone lidocaine patches 10 h after application were 1. 06, 1. 10 and 1. 66 folds (P<0. 05, 5% azone to lidocaine patch group) that of the lidocaine patch, respectively. (2) Lidocaine patches with negative electret containing 1%, 3% and 5% azone showed similar transdermal behavior to the corresponding chemical enhancer patches. (3) Lidocaine patches with positive electret containing 1%, 3% and 5% azone showed much better enhancing effect than the corresponding chemical enhancer lidocaine patches (P<0. 05). Besides, 5% azone together with positive electret showed a cooperative enhancing effect. Conclusion: Positive electret patch has better effect in enhancing transdermal delivery of lidocaine. Besides, the cooperative enhancing effect of azone with positive electret on transdermal delivery of lidocaine is in a concentration-dependent manner with azone.

Charge storage stability of electret film made of polypropylene/porous polytetrafiuoroethylene/polypropylene composite / 第二军医大学学报

Objective: To study charge storage stability of electret film made of polypropylene (PP)/porous polytetrafiuoroethylene(PTFE)/polypropylene composite. Methods: The PP/porous PTFE/PP composite electret film was prepared with porous PTFE, polyethylene(PE) and PP by heat melting technique. The charge storage stability of the electret film and transportation were evaluated by using the methods of isothermal surface potential attenuation and open-circuit thermally stimulated discharge (TSD) current spectra. Results: (1) The charge storage stability of PP/porous PTFE/PP composite electret was superior to that of PP electret made under ordinary temperature, because the space charge of PP/porous PTFE/PP electret was transferred from deep trap to flat trap during the heat melting process. (2) Satisfactory charge storage stability was observed in PP/porous PTFE/PP electret when under the condition of high humidity. Conclusion: PP/porous PTFE/PP electret film has satisfactory charge storage stability and can be used as a novel enhancer in transdermal delivery of drugs.

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.