Combination Of Microneedles Research Articles

The combination of microneedles with electroporation and sonophoresis to enhance hydrophilic macromolecule skin penetration.

The objective of the present work was to investigate the effects of 3 combinatorial techniques (microneedle (MN), electroporation (EP), and sonophoresis (SN)) on the in vitro skin permeation of the hydrophilic macromolecular compound fluorescein isothiocyanate-dextran (FD-4; molecular weight (MW) 4.4 kDa). Assessment of the in vitro skin permeation of FD-4 was performed in porcine skin. MN, EP, and SN were used as physical enhancement methods, given the potential of their various mechanisms. The total cumulative amount of FD-4 that permeated through treated skin using 2 or 3 combined methods, i.e., MN+EP, MN+SN, EP+SN, and MN+EP+SN, was investigated. Microconduits created by MN alone and in combination with the other techniques were observed under confocal laser scanning microscopy (CLSM). The histology of the treated skin was examined. In vitro skin permeation experiments revealed that the total cumulative amount of FD-4 that permeated porcine skin using 3 combined techniques (MN+EP+SN) was greater than the amount observed using a single method or 2 combinations (MN+EP, MN+SN, SN+EP). The histological images indicate no noticeable damage in the skin treated with all of the enhancement methods. These results suggest that MN+EP+SN may serve as a potentially effective combination strategy to transdermally deliver various hydrophilic macromolecules without causing structural alterations or skin damage.

Lymphatic Function and Immune Regulation in Health and Disease

Lymphatic vessels are present throughout the body, except in the central nervous system and bone marrow. The lymph nodes (LNs), spleen, and other secondary lymphoid organs (e.g., Peyer's patches) are strategically located in anatomical sites where they collect foreign antigen and antigen presenting cells to activate antigen-specific lymphocytes efficiently.1 In the peripheral tissues, specialized lymphatic capillaries—called initial lymphatic vessels—allow soluble materials and cells to enter the lymphatic system easily. The collected fluid and cells form lymph, which is transported by smooth muscle-invested collecting lymphatic vessels to the draining lymph node. The lymph node provides a highly organized microarchitecture that supports optimal immune surveillance. The “filtered” lymph fluid, as well as naive and activated lymphocytes, exit the lymph node via efferent lymphatic vessels. Lymphatic capillaries, collecting lymphatic vessels, and lymph nodes together provide protective immunity for the body. Disruptions of lymphatic function compromise immune function and result in lymphedema. In this review, we will summarize the current knowledge of how lymphatic function is altered in inflammatory states, cancer, and infection.

Combination of microneedling and glycolic acid peels for the treatment of acne scars in dark skin

Acne scars can cause emotional and psychosocial disturbance to the patient. Various modalities have been used for the treatment of acne scars like punch excision, subcision, peels, microdermabrasion, unfractionated and fractioned lasers. The latest in the treatment armamentarium is microneedling. Acne scars commonly coexist with postinflammatory hyperpigmentation. A combination of microneedling and glycolic acid (GA) peels was found to give excellent results in the treatment of such scars. The aim was to study the efficacy of a combination of microneedling with glycolic peel for the treatment of acne scars in pigmented skin. Thirty patients in the age group of 20-40 years with atrophic box type or rolling scars with postinflammatory hyperpigmentation were chosen for the study. Two groups were made. The first group comprised of 30 patients in whom only microneedling was performed once in 6 weeks for five sessions. In the second group of 30 patients, a combination of microneedling and 35% GA peels was carried out. Patients from both groups were evaluated on the basis of Echelle d'Evaluation clinique des Cicatrices d'acné classification. Based on the objective scoring and its statistical analysis, there was significant improvement in superficial and moderately deep scars (grade 1-3). There was also improvement in skin texture, reduction in postacne pigmentation in the second group. Microneedling is a simple, inexpensive office procedure with no downtime. It is safe in Indian skin (skin types III-IV). The combined sequential treatment with GA peel caused a significant improvement in the acne scars without increasing morbidity.

Combination of Microneedles with PLGA Nanoparticles as a Potential Strategy for Topical Drug Delivery

Penetration of PLGA nanoparticles in the hairless mouse skin petreated by microneedles was studied in vitro using nanoparticles containing coumarin 6 and R-phycoerythrin (R-PE) as fluorescent probe. Confocal laser scanning microscopy (CLSM) was used to visualize the distribution of nanoparticles and the high performance liquid chromatography (HPLC) was utilized to quantify the amount of the nanoparticles. The CLSM images revealed that nanoparticles (diameter 160.1± 1.97nm) could penetrate into the skin through the microconduits created with microneedles and reach the depth of more than 42.19µ m. The quantitative results showed that the amount of nanoparticles deposited in the skin increased by microneedles was about twice that in the control group in a period of 48h. However, the nanoparticle was not able to reach the receptor compartment. In additional, the penetration and the distribution of nanoparticles was significantly influenced by the particle size (diameter ranged from 160.1± 1.97nm to 288.2± 6.62nm). These results suggested that the combination of PLGA nanoparticles with microneedles could be a useful method to increase topical drug delivery and improving therapy by supplying drug reservoirs to the skin. Keywords: Double fluorescent probe, CLSM, hairless mouse skin, microneedle, nanoparticle

A physical method to enhance transdermal delivery of a tissue optical clearing agent: Combination of microneedling and sonophoresis

Various physical methods, such as microneedling, laser ablation, sonophoresis, and sandpaper, have been widely studied to enhance the transdermal delivery of tissue optical clearing (TOC) agents. A previous study demonstrated that the microneedling method could effectively enhance the permeability of a TOC agent through the skin barrier. In this study, we introduce a new physical combination method which utilizes both microneedling and sonophoresis to further enhance the transdermal delivery of a TOC agent, glycerol. Porcine skin samples were divided into a control group treated only with the microneedle roller and a test group treated with both the microneedle roller and sonophoresis. Glycerol was applied topically after microneedling. The optimal concentration and transdermal delivery efficacy of glycerol were quantitatively evaluated. A 70% glycerol solution was determined to be the optimal concentration for the combination method. The combination method resulted in approximately a 2.3-fold higher transdermal diffusion rate of glycerol when compared to the microneedling method alone. The combination method and optimal glycerol concentration effectively enhanced transdermal delivery of glycerol by accelerating the diffusion rate through the skin barrier.

Synergistic effect of iontophoresis and soluble microneedles for transdermal delivery of methotrexate

The aim of this study was to investigate the transdermal iontophoretic delivery of methotrexate, alone or in combination with microneedles, in-vitro and in-vivo using intracutaneous microdialysis in the hairless rat. The average depth of the microdialysis probe in the skin was found to be 0.54 mm. Methotrexate was stable in the presence of an applied electric field as determined by cyclic voltammetry. A current density of 0.4 mA cm(-2) applied for 60 min was used in combination with maltose microneedles to enhance delivery of methotrexate across the skin. Delivery was enhanced by iontophoresis and microneedles, both in-vitro and in-vivo. A synergistic 25-fold enhancement of delivery was observed in-vivo when a combination of microneedles and ionto- phoresis was used compared with either modality alone.

Photodynamic photorejuvenation of the face with a combination of microneedling, red light, and broadband pulsed light

High efficacy and safety, coupled with in-office, short contact protocols have made photodynamic therapy (PDT) with aminolevulenic acid (ALA) for the treatment of actinic keratoses a mainstay option over the last decade. Clinical improvement in photoaged skin has also been reported to accompany PDT treatments. The study objective was to maximize epidermal penetration and subsequent activation of ALA for the treatment of photodamaged facial skin, utilizing a microneedle roller prior to incubation and combined irradiation with red light and broadband pulsed light in a single treatment. A full-face treatment of 21 patients was performed with 630 nm light and broadband pulsed light after multiple passes with a microneedle roller and 1-hour ALA incubation. The primary endpoint was clinical improvement, scored during two separate live assessments by three physicians blinded to previous scores, using a 5-point standardized photoaging scale. The secondary endpoint was evaluation of patient satisfaction based on a quartile scale comparing baseline to 6-month post-treatment photography. Statistically significant improvement was seen in the global photoaging scores, as well as sub-components of the scale (fine lines, mottled pigmentation, sallowness, tactile roughness, and telangiectasias) at 3 months as compared with baseline live assessment, and at 6-month live assessment compared with the 3 months. In addition, 90% of patients judged clinical improvement to be greater than 50% at 6 months compared to baseline photography. Use of a microneedle roller to "pre-treat" prior to application of ALA appears to be well tolerated and allows for even absorption and perhaps deeper penetration of ALA following a defined incubation period. Use of red light and broadband pulsed light allowed for deeper activation of ALA, potentially accounting for marked clinical improvement in photoaging.

Transdermal delivery of a ~13 kDa protein—an in vivo comparison of physical enhancement methods

The availability of several enhancement techniques has made it possible to study delivery of macromolecules through skin. This study was conducted to evaluate the transdermal delivery of a ~13 kDa protein using iontophoresis, sonophoresis, and microneedles alone or in combination. In vivo delivery experiments were carried out using hairless rats with daniplestim (DP) as the model protein (molecular weight: 12.760 kDa; isoelectric point, 6.2). Delivery enhancement abilities of the above techniques were evaluated at two different drug concentrations in the patch: 2 mg/mL and 5 mg/mL. At a drug loading concentration of 2 mg/mL maximum delivery was seen with the combination of microneedles and iontophoresis. At 5 mg/mL, sonophoresis alone gave a Cmax of 8.22 ± 5.9 ng/mL and a combination of sonophoresis and iontophoresis gave a Cmax of 4.9 ± 1.8 ng/mL. The results of this study suggest that combination of microneedles and iontophoresis was the most effective approach in delivering a 13 kDa protein through the skin.