This study aimed to prepare and assess active microneedle (MN) patches based on a novel biomaterial and their effective coupled (physical and electrical) transdermal delivery of a model drug (Linezoid). Modified MN patches (e.g. fabricated from Linezoid, boronated chitosan, polyvinyl alcohol and D-sorbitol) were engineered using a vacuum micromoulding method. Physicochemical, FTIR (Fourier transform infrared), in-silico, structural and thermal analysis of prepared formulations were conducted to ascertain MN quality, composition and integrity. In-vitro mechanical tests, membrane toxicity, drug release, antibiofilm, ex-vivo mucoadhesion, insertion and in-vivo antibiofilm studies were performed to further validate viability of the coupled system. Optimized MN patch formulation (CSHP3 - comprising of 3 % w/v boronated chitosan, 3.5 % w/v PVA and 10 % w/w D-sorbitol) exhibited sharp-tipped, equi-distant and uniform-surfaced micron-scaled projections with conforming physicochemical features. FTIR analysis confirmed modification (i.e., boronation) of chitosan and compatibility as well as interaction between CSHP3 constituents. In-silico analysis indicated non-covalent interactions between all formulation constituents. Moreover, boronated chitosan-mucin glycoprotein complex showed a stronger bonding (∼1.86 times higher CScore) as compared to linezolid-mucin counterpart. Thermal analysis indicated amorphous nature of CSHP3. A ∼ 1.42 times higher tensile strength was displayed by CSHP3 as compared to control (i.e., pure chitosan, polyvinyl alcohol and D-sorbitol-based MN patch). Membrane toxicity study indicated non-toxic and physiological compatible nature of CSHP3. Within 90 min, 91.99 ± 2.3 % linezolid was released from CSHP3. During release study on agarose gel, CSHP3-iontophoresis treatment resulted in a ∼ 1.78 and ∼ 1.20 times higher methylene blue-covered area and optical density, respectively, within 60 min as compared to CSHP3 treatment alone. Staphylococcus aureus biofilms treated with CSHP3 exhibited 65 ± 4.2 % reduction in their mass. CSHP3 MN patches remained adhered to the rabbit oral mucosa for 6 ± 0.15 h. Mucosa treated with CSHP3 and CSHP3-iontophoresis combination showed a generation of pathways in the epithelium layers without any damage to the underlying lamina propria. Eradication of Staphylococcus aureus from oral mucosal wounds and complete tissue regeneration was recorded following 7-day treatment using CSHP3-iontophoresis coupled approach.

Background: Terbinafine hydrochloride (TEB) is a broad-spectrum antifungal medication commonly used to treat fungal infections of the skin. This study designed a hydrogel patch assisted by an iontophoresis system to enhance the transdermal permeability of TEB, enabling deeper penetration into the skin layers. Methods: The influences of current intensity, pH levels, and drug concentration on the TEB hydrogel patch\'s permeability were explored using an adaptive ion electroosmosis system. The pharmacokinetic profile, facilitated by iontophoresis for transdermal permeation, was analyzed through the application of microdialysis technology. Scanning electron microscopy and transmission electron microscopy were employed to assess the impact of ion electroosmotic systems on skin integrity. Results: The cumulative drug accumulation within 8 h of the TEB hydrogel patches, assisted by iontophoresis, was 2.9 and 7.9 times higher than without iontophoresis assistance and TEB cream in the control group, respectively. TEB hydrogel patches assisted by iontophoresis can significantly increase the permeability of TEB, and the AUC(0-8 h) was 3.4 and 5.4 times higher, while the Cmax was 4.2 and 7.3 times higher than the TEB hydrogel patches without iontophoresis, respectively. This system has no significant impact on deep-layer cells. Conclusions: This system may offer a safe and effective clinical strategy for the local treatment of deep antifungal infections.

The development of an effective transdermal drug delivery protocol to eccrine sweat glands is important for the advancement of research on the human sweating response. We investigated whether microneedle treatment prior to the application of pilocarpine, a hydrophilic and sudorific agent that does not induce sweating due to a limited percutaneous passive diffusion by skin application alone, augments sweat production. We applied three microneedle arrays to forearm skin sites simultaneously (n = 20). Upon removal of the microneedles, 1 % pilocarpine was applied to each site for 5-, 15-, and 30-min for the assessment of sweat gland function. In parallel, pilocarpine was administered by transdermal iontophoresis (5-min) at a separate site. Sweat rate was assessed continuously via the ventilated capsule technique. Pilocarpine augmented sweat rate at the 15- and 30-min periods as compared to the application at 5-min. The sweating responses induced by the 15- and 30-min application of pilocarpine were equivalent to ∼ 80 % of that measured at the iontophoretically treated sites. Notably, we observed a correlation in sweat rate between these two transdermal drug delivery methods. Altogether, our findings show that pre-treatment of microneedle arrays can enhance transdermal delivery efficiency of pilocarpine to human eccrine sweat glands.

BACKGROUND: Microneedles are tiny needles, typically ranging from tens to hundreds of micrometers in length, used in various medical procedures and treatments. The tested medical device named \"CELLADEEP Patch\" a dissolvable microneedle therapy system (MTS), made of hyaluronic acid and collagen. And the iontophoresis technique is also applied in the system. The study aimed to evaluate the effectiveness of the \"CELLADEEP Patch\" in skin improvement.
METHODS: Ex vivo human-derived skin tissue models were used in this study and they were divided into three different groups, namely, the Untreated Group, the Negative Control Group, and the Test Group respectively. The Untreated Group received no treatment measures, the Negative Control Group was exposed to ultraviolet B radiation (UVB) irradiation, and the Test Group was exposed to UVB irradiation and treated with \"CELLADEEP Patch\". Skin moisture content, transdermal water loss, and skin elasticity were evaluated by three clinical devices. Additionally, histological staining and related mRNA expression levels were also analyzed.
RESULTS: The results of skin moisture content, transdermal water loss, and skin elasticity evaluation consistently illustrated that the application of \"CELLADEEP Patch\" led to remarkable skin improvement. And the analysis of histological staining images also confirmed the effectiveness of the \"CELLADEEP Patch\", especially for increasing collagen density. Moreover, the upregulation of Collagen type 1 a (COL1A1) and hyaluronan synthase 3 mRNA expression and the decrease of Matrix metalloproteinase 1 (MMP-1) and Interleukin-1 beta (IL-1β) mRNA expression reflected its wrinkle improvement, moisturizing and anti-inflammation function.
CONCLUSIONS: \"CELLADEPP Patch\", the MTS combined with the iontophoresis technique, exhibits its effectiveness in moisturizing, skin elasticity improvement, and anti-inflammatory function when applied to ex vivo human-derived skin tissue models in experiments. The study has contributed to the understanding of the \"CELLADEPP Patch\" and laid the foundation for subsequent animal experiments and clinical trials.

Aim: Rose Bengal photodynamic antimicrobial therapy (RB-PDAT) has poor corneal penetration, limiting its efficacy against acanthamoeba keratitis (AK). Iontophoresis enhances corneal permeation of charged molecules, piquing interest in its effects on RB in ex vivo human corneas. Methods: Five donor whole globes each underwent iontophoresis with RB, soaking in RB, or were soaked in normal saline (controls). RB penetration and corneal thickness was assessed using confocal microscopy. Results: Iontophoresis increased RB penetration compared with soaking (177 ± 9.5 μm vs. 100 ± 5.7 μm, p < 0.001), with no significant differences in corneal thickness between groups (460 ± 87 μm vs. 407 ± 69 μm, p = 0.432). Conclusion: Iontophoresis significantly improves RB penetration and its use in PDAT could offer a novel therapy for acanthamoeba keratitis. Further studies are needed to validate clinical efficacy.
The study aimed to improve a new treatment for eye infections known as photodynamic antimicrobial therapy. It investigated whether the use of electricity through a technique called iontophoresis could help a chemical called Rose Bengal go deeper into the eye in order to target more severe infections. The iontophoresis machine was custom built, with patient-contacting components 3D printed. The experiments were performed using donated human eye tissue and found that iontophoresis significantly improved the penetration depth of Rose Bengal as compared with the current technique of only soaking the eye in Rose Bengal.

Iontophoretic transdermal drug delivery (TDD) devices are known to enhance the transdermal transport of drugs. However, conventional transdermal iontophoretic devices require external power sources, wired connections, or mechanical parts, which reduce the comfort level for patients during extended use. In this work, a self-powered, wearable transdermal iontophoretic patch (TIP) is proposed by harvesting ambient humidity for energy generation, enabling controlled TDD. This patch primarily uses moist-electric generators (MEGs) as its power source, thus obviating the need for complex power management modules and mechanical components. A single MEG unit can produce an open-circuit voltage of 0.80 V and a short-circuit current of 11.65 µA under the condition of 80% relative humidity. Amplification of the electrical output is feasible by connecting multiple generator units in series and parallel, facilitating the powering of certain commercial electronic devices. Subsequently, the MEG array is integrated with the TDD circuit to create the wearable TIP. After 20 min of application, the depth of drug penetration through the skin is observed to increase threefold. The effective promotion effect of TIP on the transdermal delivery of ionized drugs is corroborated by simulations and experiments. This wearable TIP offers a simple, noninvasive solution for TDD.

Functional gastrointestinal disorders, which had an impact on the dentofacial system (pain, loose teeth and falling out of them) in patients who have had COVID-19, drew the close attention of specialists of different profiles. The pathogenesis of worsening post-COVID edentulism is insufficiently studied, as many issues of adequate therapy remain unsolved, in which the role of non-drug technologies in the treatment of dental patients who have suffered from COVID-19 is extremely high.
OBJECTIVE: To describe the mechanism of action and clinical effectiveness of the developed combined physiotherapy method, including the induced technique of piracetam iontophoresis on the frontooccipital technic and acupuncture laser therapy in dental patients with complaints of edentulism progression after COVID-19 on the basis of the analysis of single studies on the post-COVID loss of teeth treatment.
METHODS: A number of patients equal 120 who complained of tooth loss after COVID-19 during the past 6 months were examined. The following initial and end points were considered: dental bleeding and inflammation scores, vascular and endothelial dysfunction markers - levels of intercellular adhesion molecules and their receptors (SlCAM-1, SVCAM-1, VEGF-A, ET-1) before and after treatment.
RESULTS: Negative correlation between VEGF-A (pg/ml) concentration in peripheral blood serum and sVCAM-1 (ng/ml) level in the examined patients (r=0.4830, p<0.05) and strong inverse correlation between slCAM-1 (ng/ml) level and sVCAM-1 (r=0.7696, p<0.01) have been established. More significant effects after application of the combined induced method on the head\'s structures and laser acupuncture have been noted than after acupuncture laser exposure and after inducing technique separately, namely in the form of dental inflammation score correction by 1.76 times (p<0.001), decrease of bleeding score by 2.6 (p<0.05), decrease of concentration of SVCAM-1 by 1.7 times and SlCAM-1 by 2 times (p<0.001), increase of endothelin level by 1.7 times as well as the initial low VEGF-A (pg/ml) by 1.5 times (p<0.01).
CONCLUSIONS: The developed physiotherapeutic complex, which includes laser acupuncture physiotherapy and induced technique of 5% piracetam iontophoresis, can potentially be considered as a physioprophylactic and therapeutic model of post-COVID edentulism.
Функциональные нарушения системы пищеварения, отразившиеся на зубочелюстной системе (боль, шаткость, выпадение зубов) у пациентов, перенесших COVID-19, привлекли пристальное внимание специалистов разного профиля. Патогенез прогрессирующей постковидной адентии малоизучен, как и не решены многие вопросы адекватной терапии, в которой роль немедикаментозных технологий при лечении стоматологических пациентов, перенесших COVID-19, крайне высока.
UNASSIGNED: На основе анализа единичных исследований по лечению постковидной адентии описать механизм действия и клиническую эффективность разработанной сочетанной методики физиотерапии, включающей лекарственный электрофорез пирацетама по лобно-затылочной методике и лазеропунктуру у стоматологических пациентов с жалобами на прогрессирование адентии после COVID-19.
UNASSIGNED: Обследованы 120 пациентов, обратившихся с жалобами на выпадение зубов после COVID-19 на протяжении последних 6 мес. В качестве исходных и конечных точек учитывали: стоматологические индексы кровоточивости и воспаления, маркеры сосудисто-эндотелиальной дисфункции — уровни молекул межклеточной адгезии и их рецепторы (SlCAM-1, SVCAM-1, VEGF-A, ЭТ-1) до и после лечения.
UNASSIGNED: Установлена отрицательная корреляционная связь между концентрацией VEGF-A (пг/мл) в сыворотке периферической крови и уровнем sVCAM-1 (нг/мл) у обследуемых пациентов (r=0,4830, p<0,05) и сильная обратная корреляционная связь между уровнем slCAM-1 (нг/мл) и sVCAM-1 (r=0,7696, p<0,01). После применения комбинированной методики на структуры головы и лазеропунктуры отмечали более значимые эффекты, чем после пунктурного лазерного воздействия и после методики: в виде коррекции стоматологического индекса воспаления в 1,76 раза (p<0,001), снижения индекса кровоточивости в 2,6 раза (p<0,05), снижения концентрации SVCAM-1 в 1,7 раза и SlCAM-1 в 2 раза (p<0,001), возрастания уровней эндотелина в 1,7 раза, как и исходного низкого VEGF-A (пг/мл) в 1,5 раза (p<0,01).
UNASSIGNED: Разработанный физиотерапевтический комплекс, включающий лазеропунктуру и методику лекарственного электрофореза 5% пирацетама, потенциально можно рассматривать в качестве физиопрофилактической и лечебной модели постковидной адентии.

Conservative treatments for plantar fasciitis have different levels of effectiveness, so it is necessary to personalize the therapeutic modality that improves the patients\' symptoms.
METHODS: A double-blinded randomized clinical trial was designed to evaluate the short-term efficacy of a physical treatment in chronic plantar fasciitis, namely iontophoresis, compared with radial shockwave therapy. Heel pain, health status using the EuroQol-5D questionnaire, and fascia thickness measured with ultrasound were evaluated. In total, 127 patients were randomly selected for group A and treated with iontophoresis therapy (lidocaine 0.4% and dexamethasone 0.5%), or for group B, in which they were treated with radial shockwave therapy (EWST). Measurements were taken at baseline and at follow-up during the 5 weeks of the study.
RESULTS: Statistically significant differences were observed to the shockwave therapy group in respect to the final fascia thickness, and the VAS scale (p = 0.001). The differences between groups A and B showed that the shockwave group follow-up after 3 weeks experienced complete pain remission (1.0 ± 0.9; 95%CI 0.8-1.2) and after the 6-week follow-up, complete pain remission of plantar fasciitis was observed for both therapies. Patients had a better perception of the use of EWST at the end of the treatment, although in both groups it was satisfactory (p = 0.001).
CONCLUSIONS: The results of this study showed a shorter-term effectiveness of shockwave treatment compared with the use of iontophoresis. However, both techniques were effective in satisfactorily reducing pain in this short period.

OBJECTIVE: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats.
METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis.
RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%).
CONCLUSIONS: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.

The transdermal delivery of naloxone for opioid overdose emergency purposes is a challenge due to its poor rate of diffusion through the layers of skin. This results in delayed delivery of an insufficient amount of the drug within minimal time as is desired to save lives. The ability of dissolving polymeric microneedles to shorten the lag time significantly has been explored and shown to have prospects in terms of the transdermal delivery of naloxone. This is an option that offers critical advantages to the ongoing opioid crisis, including ease of distribution and easy administration, with little to no need for intervention by clinicians. Nonetheless, this approach by itself needs augmentation to meet pharmacokinetic delivery attributes desired for a viable clinical alternative to existing market dosage forms. In this study, we report the success of an optimized iontophoresis-coupled naloxone loaded dissolving microneedle patch which had facilitated a 12- fold increase in average cumulative permeation and a 6-fold increase in drug flux over a conventional dissolving microneedle patch within 60 min of application (p < 0.05). This translates to a 30 % decrease in dose requirement in a mechanistically predicted microneedle patch established to be able to achieve the desired early plasma concentration time profile needed in an opioid overdose emergency. Applying a predictive mathematical model, we describe an iontophoresis-coupled microneedle patch design capable of meeting the desired pharmacokinetic profile for a viable naloxone delivery form through skin.