Preparation of soluble microneedles of Aconitum brachypodum alkaloids / 中成药

AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.

Preliminary study on the efficacy of subretinal injection of Aflibercept in the treatment of refractory polypoidal choroidal vasculopathy / 中华眼底病杂志

Objective:To observe the efficacy and safety of subretinal injection of Aflibercept for the treatment of refractory or recurrent polypoidal choroidal vasculopathy (PCV).Methods:A prospective clinical research. From January to June 2022, 18 patients of 18 eyes with PCV diagnosed in The Affiliated Eye Hospital of Nanchang University were included in the study. All patients underwent best corrected visual acuity (BCVA), indocyanine green angiography and optical coherence tomography (OCT). The BCVA examination was performed using the international standard visual acuity chart, which was converted to logarithm of the minimum angle of resolution (logMAR) visual acuity during statistics. The large choroidal vessel thickness (LVCT), central retinal thickness (CRT), sub-foveal choroidal thickness (SFCT) and retinal pigment epithelium detachment (PED) height were measured by enhanced depth imaging technique of OCT. The choroidal vascular index (CVI) was calculated. There were 18 patients of 18 eyes, 11 males of 11 eyes and 7 females of 7 eyes. The age was (64.22±3.86) years old. The disease duration was (5.22±1.80) years. The patient had received intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs for (7.72±1.36) times. The logMAR BCVA of the affected eyes was 1.28±0.25. The SFCT, CRT, LVCT, PED height were (436.56±9.80), (432.44±44.29), (283.78±27.10), (342.44±50.18) μm, respectively, and CVI was 0.65±0.01. All eyes were treated with a single subretinal injection of 40 mg/ml Aflibercept 0.05 ml (including Aflibercept 2.0 mg). According to the results of OCT and BCVA after treatment, the lesions were divided into active type and static type. The active lesions were treated with intravitreal injection of Aflibercept at the same dose as before. Quiescent lesions were followed up. Examinations were performed 1-3, 6, 9 and 12 months after treatment using the same equipment and methods before treatment. The BCVA, LVCT, CRT, SFCT, PED height, CVI, interretinal or subretinal fluid, lesion regression rate, injection times, and complications during and after treatment were observed. The BCVA, SFCT, CRT, LVCT, PED height and CVI before and after treatment were compared by repeated measures analysis of variance.Results:Eighteen eyes received subretinal and/or intravitreal injection of Aflibercept (1.61±0.85) times (1-4 times). At the last follow-up, the polypoid lesions regressed in 4 eyes and PED disappeared in 1 eye. Compared with before treatment, BCVA ( F=50.298) gradually increased, CRT ( F=25.220), PED height ( F=144.16), SFCT ( F=69.77), LVCT ( F=136.69), CVI ( F=72.70) gradually decreased after treatment. The differences were statistically significant ( P<0.001). Macular hole occurred in 1 eye after treatment, and the hole closed spontaneously 3 months after treatment. No serious complications such as retinal tear, retinal detachment, endophthalmitis and vitreous hemorrhage occurred during and after treatment. Conclusion:Subretinal injection of Aflibercept is safe and effective in the treatment of refractory PCV.

Wound healing in diabetic mice with soluble microneedle-loaded platelet-rich plasma lysate: a preliminary study / 中国输血杂志

【Objective】 To prepare microneedles(MNs) loaded with platelet-rich plasma lysate (PL) using Carboxymethyl chitosan (CMCS), and explore the prospect of PL MNs in the treatment of diabetic wounds. 【Methods】 CMCS was used as the basic material, and an appropriate amount of polyvinylpyrrolidone (PVPK-60) was added to prepare needle materials of different concentrations, and the optimal concentration was determined by investigating the needle formation rate, morphological characteristics and mechanical properties, and the growth factor activity in PL MNs was investigated. The diabetic mice were randomly divided into four groups after the back wound was made, the control group did not do any treatment, the PL smear group was treated with PL smearing, the blank MNs group was treated with MNs without PL, and the PL MNs group was treated with PL microneedles. The effect of PL MNs in wound healing in diabetic mice was evaluated through body observation, H&E staining and immunohistochemistry results. 【Results】 When PVPK60 was 40 mg/mL, the needle formation rate was 100%, the array was complete, the needle body was full, and the needle was sharp. According to the results of mechanical-displacement curve and weight pressure change experiment, the prepared PL MNs have good mechanical strength. The results of growth factor analysis indicated that the content of vascular endothelial growth factor (VEGF) in PL was (625±35) pg/mL, and the content of platelet-derived growth factor-BB (PDGF-BB) was (18 741±1 287) pg/mL. After making the MNs, the VEGF content was (183±2) pg/mL, and the PDGF-BB content was (8049±1157) pg/mL. Although the concentration of growth factors decreased, growth factor activity was still preserved.The results of wound healing experiments in diabetic mice showed that the PL MNs group had better healing, and the wound healing rate was different from that of three groups (P<0.01). The results of H&E staining showed that the PL MNs group had fewer inflammatory cell infiltrates and bleeding spots. The number of fibroblasts and new microvascular in the control group was worse than that in the PL MNs group and the PL smear group. The results of immunohistochemistry indicated that the expression of pro-inflammatory factor IL-6 decreased, while anti-inflammatory factor TGF-β and angiogenesis index CD31 increased in the PL MNs group, which were significantly different from those in the other three groups (P<0.01). 【Conclusion】 The PL MNs prepared in this experiment have good mechanical properties, which has a positive effect on the wound healing of diabetic mice, and provides a new idea for diabetic wound healing.

Study on preparation，characterization and in vitro transdermal properties of Xiongzhi shigao decoction soluble microneedles / 中国药房

OBJECTIVE To prepare Xiongzhi shigao decoction soluble microneedles， characterize it and investigate its transdermal properties in vitro. METHODS Two-step centrifugal method was used to prepare Xiongzhi shigao decoction soluble microneedles. The formability and mechanical property of the microneedles were evaluated from aspects of stroma fluidity， microneedle formability， needle hardness， etc. The appearance， mechanical strength， dissolution performance， skin barrier recovery performance and drug loading of the prepared microneedles were characterized by using active components of the soluble microneedle （chlorogenic acid， ferulic acid， notopterol， imperatorin， ligustilide， isoimperatorin） as indicators. The in vitro transdermal performance was investigated by Franz diffusion cell. RESULTS The soluble microneedle tips of Xiongzhi shigao decoction prepared in this study were conical， evenly distributed and of the same thickness， with good mechanical properties； the tip of the needle could be almost completely dissolved after being penetrated into the skin of rats for 2 hours， and the skin barrier recovery performance was good； the drug loading of chlorogenic acid， ferulic acid， notopterol， imperatorin， ligustilide and isoimperatorin were （87.04±1.12）， （67.69±1.23）， （20.65±0.17）， （35.00±0.11）， （153.83±0.21） and （23.52±0.50） μg per patch respectively. The results of in vitro transdermal study showed that cumulative release rates of 6 active components in this microneedle after 72 hours were 36.94%， 56.72%， 19.36%， 57.98%， 11.06% and 35.19%， respectively. CONCLUSIONS Xiongzhi shigao decoction soluble microneedles are prepared successfully in this study and have good formability， mechanical properties and pliable backing， which can significantly promote the transdermal drug delivery.

Rapidly separating dissolving microneedles with sustained-release colchicine and stabilized uricase for simplified long-term gout management

Despite growing prevalence and incidence, the management of gout remains suboptimal. The intermittent nature of the gout makes the long-term urate-lowering therapy (ULT) particularly important for gout management. However, patients are reluctant to take medication day after day to manage incurable occasional gout flares, and suffer from possible long-term toxicity. Therefore, a safe and easy-to-operate drug delivery system with simple preparation for the long-term management of gout is very necessary. Here, a chitosan-containing sustained-release microneedle system co-loaded with colchicine and uricase liposomes were fabricated to achieve this goal. This microneedle system was confirmed to successfully deliver the drug to the skin and maintain a one-week drug retention. Furthermore, its powerful therapeutic potency to manage gout was investigated in both acute gouty and chronic gouty models. Besides, the drug co-delivery system could help avoid long-term daily oral colchicine, a drug with a narrow therapeutic index. This system also avoids mass injection of uricase by improving its stability, enhancing the clinical application value of uricase. In general, this two-drug system reduces the dosage of uricase and colchicine and improves the patient's compliance, which has a strong clinical translation.

Applications and recent advances in transdermal drug delivery systems for the treatment of rheumatoid arthritis

Rheumatoid arthritis is a chronic, systemic autoimmune disease predominantly based on joint lesions with an extremely high disability and deformity rate. Several drugs have been used for the treatment of rheumatoid arthritis, but their use is limited by suboptimal bioavailability, serious adverse effects, and nonnegligible first-pass effects. In contrast, transdermal drug delivery systems (TDDSs) can avoid these drawbacks and improve patient compliance, making them a promising option for the treatment of rheumatoid arthritis (RA). Of course, TDDSs also face unique challenges, as the physiological barrier of the skin makes drug delivery somewhat limited. To overcome this barrier and maximize drug delivery efficiency, TDDSs have evolved in terms of the principle of transdermal facilitation and transdermal facilitation technology, and different generations of TDDSs have been derived, which have significantly improved transdermal efficiency and even achieved individualized controlled drug delivery. In this review, we summarize the different generations of transdermal drug delivery systems, the corresponding transdermal strategies, and their applications in the treatment of RA.

Nilotinib-loaded gelatin methacryloyl microneedles patch for the treatment of cardiac dysfunction after myocardial infarction / 生物医学工程学杂志

The study aimed to evaluate the therapeutic effect of nilotinib-loaded biocompatible gelatin methacryloyl (GelMA) microneedles patch on cardiac dysfunction after myocardial infarction(MI), and provide a new clinical perspective of myocardial fibrosis therapies. The GelMA microneedles patches were attached to the epicardial surface of the infarct and peri-infarct zone in order to deliver the anti-fibrosis drug nilotinib on the 10th day after MI, when the scar had matured. Cardiac function and left ventricular remodeling were assessed by such as echocardiography, BNP (brain natriuretic peptide) and the heart weight/body weight ratio (HW/BW). Myocardial hypertrophy and fibrosis were examined by WGA (wheat germ agglutinin) staining, HE (hematoxylin-eosin staining) staining and Sirius Red staining. The results showed that the nilotinib-loaded microneedles patch could effectively attenuate fibrosis expansion in the peri-infarct zone and myocardial hypertrophy, prevent adverse ventricular remodeling and finally improve cardiac function. This treatment strategy is a beneficial attempt to correct the cardiac dysfunction after myocardial infarction, which is expected to become a new strategy to correct the cardiac dysfunction after MI. This is of great clinical significance for improving the long-term prognosis of MI patients.

Preparation of tanshinone IIA self-soluble microneedles and its inhibition on proliferation of human skin fibroblasts / 中草药·英文版

OBJECTIVE@#Hypertrophic 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).@*METHODS@#Tanshinone 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.@*RESULTS@#With 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.@*CONCLUSION@#The prepared TSA self-soluble microneedles is helpful in solving the problem of hypertrophic scars, with a stable dermal retention effect after process optimization.

Wearable patches for transdermal drug delivery

Transdermal drug delivery systems (TDDs) avoid gastrointestinal degradation and hepatic first-pass metabolism, providing good drug bioavailability and patient compliance. One emerging type of TDDs is the wearable patch worn on the skin surface to deliver medication through the skin. They can generally be grouped into passive and active types, depending on the properties of materials, design principles and integrated devices. This review describes the latest advancement in the development of wearable patches, focusing on the integration of stimulus-responsive materials and electronics. This development is deemed to provide a dosage, temporal, and spatial control of therapeutics delivery.

Analgesic effect of local anesthesia combined with nerve block anesthesia on golden micro-needles for improving facial aging / 中华医学美学美容杂志

Objective:To observe the analgesic effect of local anesthesia combined with nerve block anesthesia on golden microneedles for improving facial aging.Methods:Between December 2018 and December 2019 in Burn and Plastic Surgery of Nanchong Central Hospital, sixty female patients (between 30 and 58 years old, with an average of 45.2 years old) with natural facial skin aging were randomly divided into two groups: Group A: surface anesthesia group (30 cases); Group B: local anesthesia combined with nerve block anesthesia (30 cases). Intraoperative and postoperative pain scores, length of operation, and incidence of adverse reactions were compared between groups A and B.Results:Pain score during surgery was (6.90±0.96) points in Group A, (3.63±0.72) points in Group B. The difference between the two groups was statistically significant ( t=14.93, P<0.05); Pain score at 30 minutes after operation was (2.03±0.62) in Group A, (0.77±0.73) in Group B, the difference between the two groups was statistically significant ( t=7.28, P<0.05). There was no statistically significant difference between the two groups in the pain score at 24 hours after operation ( P>0.05); The operation process in group B was simplified, and the treatment time was significantly shortened. The difference between the two groups was statistically significant ( t=17.93, P<0.05). Conclusions:The method of local anesthesia combined with nerve block anesthesia is used in the treatment of gold microneedles to improve the analgesic effect in facial aging, which significantly shortens the treatment time and has fewer adverse reactions. This method is worth popularizing.

Preparation of triptolide-loaded dissolving microneedles and its transdermal penetration / 中国中药杂志

Triptolide(TP), the main active and toxic component of Tripterygium wilfordii, has the limitations of low bioavailability, poor absorption, low concentration in plasma, and small lethal dose. Microneedle(MN), the hybrid of hypodermic needle and transdermal patch, is a physical penetration-enhancing system. Dissolving microneedles(DMNs) can be tailored to specific needs of degradation rate. In this study, the TP-loaded DMNs(DMNs-TP) were prepared with the two-step centrifugation method. The optimal ratio of PVA to PVP K30, water content in matrix solution, demoulding method, and plasticizer for preparing DMNs were investigated with the indexes of formability and mechanical strength. The drug loading capacity was determined by HPLC and morphological characteristics were observed under an optical microscope. The mechanical properties were investigated by H&E staining and Franz diffusion cell was used to detect the in vitro skin permeation characteristics. Through the experiment, we confirmed that the optimal backing material should be PVA and PVP K30(3∶1) and the optimal ratio of matrix material to water should be 3∶4. The prepared DMNs-TP were pyramidal with smooth surface and length of approximately 550 μm. Each patch(2.75 cm~2) had the drug loading capacity of(153.41±2.29) μg, and TP was located in the upper part of the needle. The results of in vitro skin permeation assay demonstrated that the cumulative penetration of TP in DMNs-TP reached 80% in 24 h, while little TP solution penetrated the skin, which proved that DMNs promoted the transdermal delivery of TP.

TPGS/hyaluronic acid dual-functionalized PLGA nanoparticles delivered through dissolving microneedles for markedly improved chemo-photothermal combined therapy of superficial tumor

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT).

Effects of metal or dissolving microneedles and its parameters of operation on the formation and closure of skin microchannels / 药学学报

To investigate the influence factors and effects of metal or dissolving microneedles on the formation and healing of skin microchannels, the pencil-shaped or conical stainless steel microneedles with different lengths, tip to tip space and base area, and the pencil-shaped dissolving microneedles with different tip to tip space were used. The microneedles were applied to the skin of epilatory mice and rats, and the effects of various microneedle parameters, application parameters, and animals on the microchannels were explored by the transepidermal water loss (TEWL) and methylene blue staining. Visually observe the skin local irritation caused by the microneedles. The animal experiments were approved by the Animal Experiments Welfare and Ethical Committee of Zhejiang University of Technology. The application time of the microneedle should be maintained at 30 s or more. When the insertion forces were 2, 4, 8 N, and the TEWL initial values of the formed microchannels were 12.9, 33.0, 40.4 g·m-2·h-1, respectively. When the length of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 37.1, 40.4, 49.5 g·m-2·h-1, respectively. When the tip to tip space of metal microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 33.2, 40.4, 55.8 g·m-2·h-1, respectively. When the base area of metal microneedle were 0.16, 0.35, 0.62 cm2, and the TEWL initial values of the formed microchannels were 35.1, 40.4, 67.1 g·m-2·h-1, respectively. The effects of conical and pencil-shaped microneedles are similar. When the tip to tip space of pencil shaped dissolving microneedle were 400, 600, 800 μm, and the TEWL initial values of the formed microchannels were 49.8, 60.5, 70.5 g·m-2·h-1, respectively. The TEWL baseline values of animal skins of different genders and series are different, but the tendency of microchannels formation and closure is similar. Visual inspection revealed that the slight erythema caused by the microneedles subsided within 24 h. Microneedles of different parameters have different effects on microchannels. The microchannels closed within 24 or 48 h, and the skin local irritation caused by microneedle was mild.

Recent advances in microneedles-mediated transdermal delivery of protein and peptide drugs

Proteins and peptides have become a significant therapeutic modality for various diseases because of their high potency and specificity. However, the inherent properties of these drugs, such as large molecular weight, poor stability, and conformational flexibility, make them difficult to be formulated and delivered. Injection is the primary route for clinical administration of protein and peptide drugs, which usually leads to poor patient's compliance. As a portable, minimally invasive device, microneedles (MNs) can overcome the skin barrier and generate reversible microchannels for effective macromolecule permeation. In this review, we highlighted the recent advances in MNs-mediated transdermal delivery of protein and peptide drugs. Emphasis was given to the latest development in representative MNs design and fabrication. We also summarize the current application status of MNs-mediated transdermal protein and peptide delivery, especially in the field of infectious disease, diabetes, cancer, and other disease therapy. Finally, the current status of clinical translation and a perspective on future development are also provided.

Preparation of neurotoxin loaded dissolving microneedles and its transdermal penetration / 中草药

Objective: To prepare Naja atra neurotoxin (NT) loaded dissolving microneedles (DMNs-NT), and investigate the physicochemical properties and in vitro transdermal properties. Methods: DMNs-NT was prepared by a two-step centrifugation method. The ratio of CS and PVP K30, the water content of the matrix solution, and the backing layer material were optimized by the indexes of formability and mechanical strength of the microneedles and flexibility of the backing layer. The drug loading content was determined by HPLC, and the morphological characteristics were observed under an optical microscope, and the stability was also examined. Franz diffusion cell was used to investigate its in vitro skin permeation characteristics. Results: Through the single-factor exploration, we confirmed that the optimal prescription technique for DMNs-NT preparation was a 1:1 ratio of CS and PVP k30, a 5:4 ratio of matrix material and water, with CMC as the backing layer material. The DMNs-NT had a pyramidal shape with a smooth surface and a length of approximately 500 μm. The drug loading content of per tablet was (15.4 ± 0.5) μg. The drug was located in the upper part of the needle. DMNs-NT had good stability within 3 months. The results of in vitro skin permeation assay showed that the cumulative penetration of NT in DMNs-NT could reach 95.8% in 4 h, while NT solution barely penetrated the skin, which proved that it had a good promoting effect on NT transdermal delivery. Conclusion: In this study, DMNs-NT had good mechanical properties and good skin penetration, which realized the transdermal drug delivery of macromolecular drugs.

Optimization of Preparation Process of Fast-Dissolving Microneedles by Box-Behnken Method / 中国药学杂志

OBJECTIVE: To optimize the formulation and preparation process of fast-dissolving PVP microneedles, and provide a high-quality carrier for PVP drug-loaded microneedle research. METHODS: On the basis of single factor, the needle tips dissolution time and insertion ratio were used as the evaluation indexes, and the optimal preparation process of microneedle was optimized by Box-Behnken method. RESULTS: From the single factor test and the Box-Behnken test, it was known that the optimum preparation conditions were as follows: the needle tip concentration was 0.70 g•mL-1, the temperature was 40 ℃, and the humidity was 40%. The microneedle height was 600 μm, the width was 200 μm, the pitch was 500 μm, quadrangular pyramid. The area of the microneedle patch was 0.56 cm2, the dissolution time in water was (41.00±3.74)s, and the insertion ratio was (93.19±5.25)%. CONCLUSION: The PVP fast-dissolving microneedles can be prepared simply and conveniently by the Box-Behnken method, which provides a reference for the preparation of further drug-loaded microneedles.

Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats

Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location (acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli (ST36) acupoint using microneedles containing thymopentin. The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.

Physical methods for topical skin drug delivery: concepts and applications

Topical drug delivery is an interesting approach to treat skin diseases and to avoid pain and low patient compliance in cases where a systemic delivery is required. However, the stratum corneum, which is the outermost skin layer, strongly protects the body from the entrance of substances, especially those hydrophilic. In this context, different physical methods have been studied to overcome the stratum corneum barrier and facilitate penetration of drugs into or through the skin. Among them, iontophoresis, low-frequency ultrasound and microneedles have been widely employed for transdermal drug delivery. More recently, they are also studied to aid in the treatment of dermatological disorders, such as skin tumors and inflammation. Basically, iontophoresis refers to the movement of charged and non-charged hydrophilic molecules through the skin due to the application of a low constant electric current and the contributions of electromigration and electroosmosis. In low-frequency ultrasound, cavitation is the main mechanism for skin permeabilization that consists on the formation of microbubbles that disorganize the stratum corneum. Microneedles are microprojections, minimally invasive, that can be designed with different lengths, materials and geometry to increase skin permeability. In this review, concepts, mechanisms and applications of these three physical methods will be presented and discussed with focus on their use in dermatological treatments. Moreover, comparative studies using different physical methods will be presented and also some clinical perspectives will be addressed

Microneedles: quick and easy delivery methods of vaccines

Vaccination is the most efficient method for infectious disease prevention. Parenteral injections such as intramuscular, intradermal, and subcutaneous injections have several advantages in vaccine delivery, but there are many drawbacks. Thus, the development of a new vaccine delivery system has long been required. Recently, microneedles have been attracting attention as new vaccination tools. Microneedle is a highly effective transdermal vaccine delivery method due to its mechanism of action, painlessness, and ease of use. Here, we summarized the characteristics of microneedles and the possibilities as a new vaccine delivery route.

Enhancement of skin permeation of vitamin C using vibrating microneedles

This study was performed to evaluate the use of vibrating microneedles for the transdermal delivery of vitamin C. The microneedles were designed to vibrate at three levels of intensity. In vitro permeation by vitamin C was evaluated according to the specific conditions such as vibration intensity (levels 1, 2 and 3), application time (1, 3, 5, 7 and 10 min), and application power (500, 700 and 1,000 g). The highest permeation of vitamin C was observed at level 3 of vibration intensity, 5 min of application, and 1,000 g of application power. Vitamin C gel showed no cytotoxic effect against Pam212 cells or skin irritation effects. A pharmacokinetic study of the gel in rats was conducted under optimized conditions. The AUC₀-∞ and C(max) increased 1.35-fold and 1.44-fold, respectively, compared with those after vitamin C gel without application with vibrating microneedles. The present study suggests that vibrating microneedles can be used to facilitate the skin permeability of vitamin C under optimal conditions.