Local Administration Research Articles

CD1530, selective RARγ agonist, facilitates Achilles tendon healing by modulating the healing environment including less chondrification in a mouse model

AbstractHeterotopic ossification (HO) in Achilles tendon often arises due to endochondral ossification during the healing process following trauma. Retinoic acid receptor γ (RARγ) plays a critical role in this phenomenon. This study aims to elucidate the therapeutic effects of CD1530, an RARγ selective agonist, along with the contributing cells, in Achilles tendon healing, utilizing a cell lineage tracing system. Local injection of CD1530 facilitated histological tendon healing by inhibiting chondrification in a mouse Achilles rupture model. Resident Scleraxis (Scx)+ cells in Achilles tendon were not found to be actively involved in HO or tendon healing following injury. Instead, these processes were primarily driven by tendon stem/progenitor cells (TSPC)‐like cells. Furthermore, an in vitro assay revealed that CD1530 attenuated inflammation in injured Achilles tendon‐derived tendon fibroblasts (iATF) and inhibited the chondrogenesis of iATF. This dual effect suggests the potential of CD1530 in effectively modulating the healing environment during tendon healing. Together, the present study demonstrated that the local administration of CD1530 accelerated tendon healing by modulating the healing environment, including reducing chondrification via targeting TSPC‐like cells in a mouse Achilles tendon rupture model. These results suggest that CD1530 may have the potential to be a novel tendon therapy that offers benefits via the inhibition of chondrogenesis.

A Mucous Permeable Local Delivery Strategy Based on Manganese-Enhanced Bacterial Cuproptosis-like Death for Bacterial Pneumonia Treatment.

Bacterial pneumonia is one of the most challenging global infectious diseases with high morbidity and mortality. Considering the antibiotic abuse and resistance of bacterial biofilms, a variety of metal-based materials have been developed. However, due to the high oxygen environment of the lungs, some aerobic infection bacteria have high tolerance to oxygen and ROS, and most of the metal-based materials based on ROS may not achieve good therapeutic effects. Inspired by the sensitivity of cuproptosis to aerobic respiratory cells, we designed a copper composite antibacterial nanoparticle and found that it can effectively induce cuproptosis-like death in the aerobic bacteria of the lungs. To address the challenge of in vivo application of cuproptosis, manganese dioxide was first incorporated to deplete protective glutathione, which can interact with copper and thus hinder the interaction of copper with proteins and assist in antibacterial action through immune enhancement. Cuproptosis-like death also requires a large number of copper ions. To meet this demand, we deliver positively hydrophilic modified composite nanoparticles that effectively penetrate the lung mucus layer directly to the lungs through local administration, and the copper ions are further released rapidly by the acidic environment at the infected site, which can further destroy bacterial biofilms in synergy with manganese. This drug-delivery system can effectively treat pneumonia caused by aerobic bacteria and avoid systemic toxicity that can be caused by large doses of copper.

Effectiveness of phentolamine mesylate, vibration and photobiomodulation in reducing pain and the reversal of local anesthesia: A systematic review.

Dental anesthesia administration often triggers unpleasant sensations, particularly needle injection-related pain, which can evoke fear among patients, especially in the pediatric population. Vibration and low-level laser therapy (LLLT) have been extensively studied as potential methods for alleviating pain. Additionally, phentolamine mesylate (PM) has shown promise in reducing the duration of anesthesia. From a clinical perspective, inadequate control over the persistence of the anesthetic effect may lead to complications associated with its prolonged duration, such as self-injuries or functional impairments. This review aimed to systematically summarize and compare methods of alleviating pain during local anesthesia and reducing its duration. In November 2023, an electronic search was systematically conducted across PubMed, Web of Science, and Scopus databases using keywords (pain) AND (anesthesia) AND ((phentolamine) or (vibration) or (LLLT) OR (PBM)). The initial pool consisted of 495 records, from which 241 duplicates were eliminated. After careful examination of the remaining articles, 40 were included. The study adhered to the PRISMA guidelines. Most studies reported beneficial effects of LLLT and vibration; however, some did not corroborate these findings. Four studies had inconclusive results. Regarding anesthesia duration involving PM and LLLT, the majority of studies exhibited notable reductions, although no significant differences were revealed in 1 study. Vibration and LLLT appear to be advantageous methods in alleviating pain associated with local anesthesia administration. Phentolamine mesylate and LLLT are efficient in reversing local anesthesia.

Allergic clinical symptoms and distribution of stimulation index of drug lymphocyte stimulation test for local anesthetics.

The Drug Lymphocyte Stimulation Test (DLST), recognized for its safety as an allergy diagnostic modality, has been acknowledged for its utility in diagnosing drug-induced pathological conditions. However, reports elucidating DLST outcomes concerning local anesthetics are notably scarce. An exhaustive analysis was conducted on the DLST results pertaining to local anesthetics derived from 571 patients presenting with suspected allergies to these specific agents. Remarkably, Stimulation Index (SI) > 1.8 was discerned in 11.4% and 7.8% of patients exhibiting hives or swelling subsequent to the administration of local anesthetics, surpassing the incidence observed in those experiencing post-injection discomfort. Additionally, SI > 3.0 was observed in 3 cases with lidocaine, 3 cases with prilocaine, and 1 case with mepivacaine. The distribution of SI exhibited a non-normal pattern for all three tested local anesthetics. Noteworthy is the case of a singular patient registering an SI of 1.84, who also yielded a positive challenge test, conclusively confirming an allergy to lidocaine. The DLST, holding promise as a potentially invaluable tool in identifying the causative factors behind adverse reactions to dental local anesthetics, lacks sufficient evidence to substantiate its efficacy definitively at present. DLST, coupled with intradermal testing and challenge testing, may be elucidated in patients exhibiting indicators of suspected local anesthetic allergy.

The SQ tree sublingual immunotherapy tablet is effective and well tolerated in children-A pivotal phase III trial.

Allergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT-tablet in a paediatric population (5-17 years) with moderate-to-severe AR/C induced by pollen from birch and trees in the birch homologous group. Nine hundred and fifty-two subjects were randomized (1:1) to daily treatment with SQ tree SLIT-tablet or placebo for up to 52 weeks and had free access to AR/C symptom-relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS). SQ tree SLIT-tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment-related adverse events were mild or moderate local administration site reactions. This is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT-tablet in tree pollen-induced AR/C in a paediatric population (5-17 years).

Controlled Stimulus-Responsive Delivery Systems for Osteoarthritis Treatment

Osteoarthritis (OA), a common and disabling degenerative joint disease, affects millions of people worldwide and imposes a considerable burden on patients and society due to its high prevalence and economic costs. The pathogenesis of OA is closely related to the progressive degradation of articular cartilage and the accompany inflammation; however, articular cartilage itself cannot heal and modulate the inflammation due to the lack of nerves, blood vessels, and lymph-vessels. Therefore, reliable and effective methods to treat OA remain highly desired. Local administration of drugs or bioactive materials by intra-articular injection of the delivery system represents a promising approach to treat OA, especially considering the prolonged joint retention, cartilage or chondrocytes targeting, and stimuli-responsive release to achieve precision OA therapy. This article summarizes and discusses the advances in the currently used delivery systems (nanoparticle, hydrogel, liposome, and microsphere) and then focuses on their applications in OA treatment from the perspective of endogenous stimulus (redox reactions, pH, enzymes, and temperature) and exogenous stimulus (near-infrared, magnetic, and ultrasound)-responsive release. Finally, the challenges and potential future directions for the development of nano-delivery systems are summarized.

Research on the protection of intangible cultural heritage and sustainable development of city brands—Taking Jingdezhen as an example

This research aims to examine the intricate connection between the preservation of intangible cultural assets and the promotion of city brands, using Jingdezhen, known as the “Porcelain Capital” of China, as a case study. Through an exploratory investigation, the study highlighted two distinct yet significant issues: the recognition of Jingdezhen’s intangible cultural assets, encompassing folklore, rituals, traditional ceramic skills, and artwork, and the economic effects resulting from cultural tourism. The research delineates the obstacles encountered by Jingdezhen in relation to urbanization, industrialization, and globalization subsequent to its establishment as the principal production hub for Chinese blue and white porcelain. Additionally, it highlights the decline of traditional ceramic skills and expertise, as community members who relied on handicrafts for their livelihoods were affected by the closure of companies. Subsequently, it elucidates the potential prospects arising from cultural tourism and the consequential economic influence of this progress on the local economy and the community’s quality of life. The report delineates community engagement initiatives and collaborative partnerships with local enterprises, colleges, government agencies, and Jingdezhen communities to use the city’s abundant cultural legacy. This research provides a comprehensive overview and assessment of the most effective methods, as identified by international studies, for incorporating the safeguarding of intangible cultural assets into sustainable urban development. Concisely, the paper offers guidance to stakeholders, the local administration, and its legislators. The statement emphasizes the necessity of implementing a comprehensive policy framework in Jingdezhen to safeguard its intangible cultural heritage and promote urban development. The objective is to achieve sustainable growth by leveraging the city’s cultural assets. The results serve as a benchmark for other cities and towns to use their cultural legacy in order to establish a sustainable city brand. Additionally, they make a valuable addition to the worldwide discourse on striking a balance between cultural preservation and economic development.

Effect of electronic fibrobronchoscope alveolar lavage combined with local administration of budesonide on the efficacy of Mycoplasma pneumoniae pneumonia in children

This study investigates the effect of electronic fibrobronchoscope alveolar lavage combined with local administration of budesonide on the efficacy of treating Mycoplasma pneumoniae pneumonia (MPP) in children. A retrospective analysis was conducted on the clinical data of 100 children with MPP treated at our hospital from April 2022 to April 2024. The patients were divided into an experimental group (50 cases) and a control group (50 cases) based to the treatment method. Both groups received routine treatment, however, the control group was treated with electronic fibrobronchoscope alveolar lavage alone, while the experimental group received electronic fibrobronchoscope alveolar lavage combined with local administration of budesonide. The efficacy of the two treatments was compared. The experimental group showed a significantly higher overall effective rate than the control group (p<0.05). After treatment, the time for cough relief, lung rales resolution, fever reduction, and hospital stay were significantly shorter in the experimental group compared to the control group (p<0.05). One week after treatment, the levels of tidal volume, vital capacity, and peak expiratory flow in the experimental group were higher than those in the control group (p<0.05). Post-treatment levels of WBC and CRP were lower in the experimental group than in the control group (p<0.05). Additionally, the incidence of complications in the experimental group was lower than in the control group (p<0.05). Electronic fibrobronchoscope alveolar lavage combined with local administration of budesonide improves the efficacy of treatment for children with MPP, enhances clinical indicators, reduces inflammation levels, and has high safety, making it worthy of clinical promotion.

“What benefits do homeless systems get from by-name data?”

ABSTRACT Built for Zero (BFZ) is a novel data-driven method to manage entries into and exits from homeless systems that is gaining popularity throughout the Global North. By-name data (BND) is the cornerstone of BFZ that gives local administrators up-to-date information about who enters, occupies, and exits their homeless system. A small body of research has analysed BFZ implementation, but neglected the benefits administrators reportedly get from BND. This paper extends that literature by answering the question: What benefits do homeless systems get from BND? The author uses interview data from administrators at 28 BFZ communities (n = 35) across the USA to answer that question. Participants said BND enhanced the efficiency, fairness, and capacity of their homeless system. This observation extends previous research by identifying ways this kind of data can help local administrators reduce the frequency and/or length of homelessness in their community. The author discusses policies and future research that are needed to maximize the benefits of BND.

Discharge estimation using a rating curve developed for the Upper Erer River, Wabisheble River Basin, Ethiopia

ABSTRACT The measurement of a stream flow is a vital component of water quality monitoring, geomorphology, and flooding investigations. However, the direct measurements of stream flow can be costly and challenging. To obtain a continuous record of discharge, typically the recorded stage and discharge are computed from the correlation of stage and discharge in the form of a rating curve. This study focused on the estimation of flow discharges using a rating curve equation based on data recorded at the Erer-Jijiga Bridge hydrometric station at the outlet of the upper Erer Sub-basin in Ethiopia for 2020–2021. The fitted rating curve was then used to estimate discharges from continuously recorded stages. The installation and operation of a gauging station in the Upper Erer Sub-basin will provide local and regional water sector administrators with more reliable estimates of discharge than would be available if the sub-basin was ungauged. This will also assist the local water sector to undertake water resource planning in the Upper Erer River Basin to better use the limited water resources in the region.

European waste management regulations in Spanish local administrations: Compliance assessment and integration Frontiers

AbstractThis research analyzes the impact of European directives, particularly the Waste Framework Directive, on municipal waste management in Spain, with a focus on Law 7/2022 promoting circular economy principles. Through an assessment of waste management ordinances in 980 municipalities, the study found that over 60% of local ordinances have not yet fully incorporated the latest regulatory requirements, indicating significant delays in adapting to European regulations. The findings reveal notable disparities in compliance, with larger municipalities showing higher adaptation rates compared to smaller ones. Additionally, regions like Catalonia and the Balearic Islands have adopted innovative approaches, including ‘pay‐as‐you‐throw’ schemes and community composting. The study underscores the critical need for better integration of circular economy principles, enhanced monitoring, and increased public awareness to promote sustainable waste management practices. By identifying regulatory gaps, this research aims to provide practical insights for improving local waste management policies and fostering greater compliance with EU mandates.

Local delivery of soluble fractalkine (CX3CL1) peptide restores ribbon synapses after noise-induced cochlear synaptopathy

Cochlear ribbon synapses between sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are vulnerable to rapid and primary damage and/or loss due to noise overexposure. Such damaged ribbon synapses can repair spontaneously in mouse and guinea pig. However, the mechanisms for synaptic repair are unclear. Previously, we have demonstrated a critical role for the fractalkine signaling axis (CX3CL1-CX3CR1) in synaptic repair, wherein noise-damaged ribbon synapses are spontaneously repaired in the presence of fractalkine receptor (CX3CR1) expressed by cochlear macrophages. Here, we examined whether local administration of chemokine fractalkine ligand (CX3CL1 or FKN) in the form of a peptide is effective in restoring synapses and hearing loss after noise-induced cochlear synaptopathy (NICS). Specifically, the efficacy of different isoforms of FKN was evaluated for restoration of loss of IHC ribbon synapses and hearing after NICS. A single transtympanic injection of soluble isoform of FKN (sFKN) peptide at 1 day after synaptopathic noise trauma for 2 hours at 93 decibel sound pressure level led to significant recovery of auditory brainstem response (ABR) thresholds, ABR peak I amplitudes and ribbon synapses in FKN knockout mice when compared to mice injected with membrane-bound FKN peptide (mFKN). Likewise, local treatment with sFKN peptide in FKN wild type mice restored synaptopathic noise-damaged ribbon synapses and ABR peak I amplitudes. Mechanistically, FKN regulates macrophage numbers in the damaged cochlea and in the absence of macrophages, sFKN failed to restore loss of synapses and hearing after NICS. Furthermore, sFKN treatment attenuated cochlear inflammation after NICS without altering the expression of CX3CR1. Finally, injected sFKN peptide was detectable inside the cochlea for 24 h localized to the basilar membrane and spiral lamina near the sensory epithelium. These data provide a proof-of-principle that local delivery of an immune factor, sFKN is effective in restoring ribbon synapses and hearing loss after NICS in a macrophage-dependent manner and highlights the potential of sFKN as an immunotherapy for cochlear synaptopathy due to noise.

Socio-economic transformation follows environmental change on Svalbard

The European Arctic, which includes the Svalbard archipelago, is situated in one of the areas showing most notable changes due to global warming and associated cascade events and processes. The main driving factor, temperature rise, is continuing to cause a large-scale overall decline in ice, from glacier retreating, less coastal land-fast ice to thinning and shrinking of open-sea pack ice. This, together with increased inflow of Atlantic waters, is causing profound changes in the local fauna, food web and biodiversity. In parallel, changes in landscape are also notable, mainly due to increasing coastal erosion and glacial melt. Over the past decades, both the traditional hunting-trapping lifestyle and mining have declined almost to the point of non-existence. At the same time, destination tourism and scientific research have become the major industries, both associated with an increase in the size of the main settlement of Longyearbyen, and thus also service jobs and local administration. Along with the shrinking of the glaciated Arctic landscape, the archipelago exemplifies the broadest level of nature protection in Europe. Strict environmental regulations that restrict and even prohibit human activities in large areas contribute to Svalbard being one of the best formally protected wilderness environments in the entire Arctic. Thus, as Svalbard marine ecosystems continue to change, they also are becoming more accessible to humans, and so also anthropogenic pressures are both changing and increasing in extent. We provide a compilation of both ecosystem components and human activities, together with indications of how these are, in parallel, changing. This forms the basis for future ecosystem and societal valuation assessments.

The Impact of Local Ketamine on Spatial Cognition Through Dopamine

The dopamine system plays a crucial role in maintaining spatial cognitive functions. Ketamine, a non-competitive NMDA receptor antagonist, indirectly affects dopamine release and function by modulating glutamatergic neuronal activity, leading to spatial cognitive impairments. This study aims to explore the specific mechanisms through which local ketamine administration affects spatial cognition. By injecting ketamine into the hippocampus of mice and combining behavioral experiments with brain tissue analysis, we found that ketamine-induced dopamine damage significantly impairs the mice’s spatial orientation abilities. This discovery offers new insights into the negative impact of ketamine addiction on cognitive function.

Denison’s Culture Model in the Context of Romanian Prefectures. Is There Room for Improvement?

Organizational culture and its importance have become common knowledge over the years, but do we really understand its influence, especially on the effectiveness of public institutions? We often talk about increasing performance, transparency and involvement in the lives of citizens to improve their quality of life, sometimes without looking at how public entities function. Therefore, this study wants to understand how exactly the organizational culture affects the Romanian Prefectures and what is the perception of their employees regarding their mission, adaptability, involvement and consistency. Since it is the responsibility of the prefectures to ensure the implementation of government policies at the local level, besides their important role in verifying the legitimacy of the administrative acts issued by the local public administration, it is imperative to see what role organizational culture plays and how it influences the group dynamics, their adaptability to change and their responsiveness. Using Denison’s model, we can analyze the perceived level of performance, effectiveness and what types of synergies are formed at the group level. Understanding the main patterns in the prefectures can support our efforts to build more resilient, flexible and adaptable structures, much needed characteristics in essential structures such as these.

Topical Anesthesia in Cutaneous Head and Neck Surgery: A Randomized Controlled Trial.

Cutaneous head and neck surgery can safely and effectively be performed using local anesthetic (LA). However, optimizing pain management during LA administration is paramount for patient comfort and procedural efficacy. The primary objective of this study was to investigate the comparative effectiveness of EMLA cream and ethyl chloride (EC) spray in mitigating pain associated with LA administration in cutaneous head and neck surgery. Randomized controlled trial. University-affiliated tertiary head and neck oncology center. Sample size calculation was performed followed by computer randomization into the following groups: EMLA, EMLA placebo (aqueous cream), EC, and a control group (no topical agent). Demographics, pain, and procedural experience scores were recorded perioperatively. Statistical analysis was performed to analyse differences between groups utilizing the Mann-Whitney U test, Kruskall-Wallis test, Chi-square test, and Spearman's Rho. 121 cutaneous lesions with a median patient age of 76 were analyzed. There were no statistically significant differences in pain scores (median [IQR]) between patients receiving EMLA (4 [3.75]), EMLA placebo (4.8 [3.6]), EC (5.8 [2.8]), and no treatment (5 [4.1], P = .19). Procedural experience scores were clinically similar (P = .02). Risk factors associated with elevated nociceptive sensitivity were surgical site (scalp, P = .01), malignant lesions (P < .01) and lesion surface area (rs = 0.22, P = .01). EMLA and EC did not mitigate LA-associated pain in patients undergoing cutaneous head and neck surgery and as such practitioners should reconsider their use of these in this regard. Patients' operative experience remains excellent regardless of topical anesthetic use. Ib.

Effects of metformin phonophoresis and exercise therapy on pain, range of motion, and physical function in chronic knee osteoarthritis: randomized clinical trial

BackgroundKnee osteoarthritis (KOA) is a common musculoskeletal disorder. Therapeutic ultrasound (US) is a safe and effective treatment for KOA. It relieves knee pain and enhances function. Metformin (MF) regulates chondrocytes, hence providing chondroprotection. Furthermore, it efficiently reduces knee articular cartilage degeneration and retards the progression of osteoarthritis. However, the localized administration of MF by phonophoresis for KOA has yet to be studied.PurposeTo assess the possible effects of metformin phonophoresis (MFPH) plus exercise therapy (EX) compared to MFPH alone or the US on knee pain, function, and range of motion (ROM) in chronic KOA patients.MethodsSeventy-eight patients with unilateral mild to moderate chronic KOA were included. Patients were randomly assigned to three groups: group A (MFPH + EX), group B (MFPH alone), and group C (US). The US group used an acoustic-neutral gel, while the MFPH group used a gel containing 1.2% MF. The exercises included hamstring stretches, calf stretches, and knee strengthening exercises. Treatment in the three groups continued for four weeks (three sessions per week). The Visual Analog Scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the goniometer were used to assess knee pain, function disability, and ROM, respectively. All measures were recorded before, 2 weeks, and 4 weeks after the intervention in all groups. Multivariate Analysis of Variance (MNOVA) was performed to compare the effects within and between groups for knee ROM and function disability. The Kruskal-Wallis test and the Friedman test analyzed the pain intensity.ResultsWhen the baseline patient characteristics were compared, there were no significant differences in means of age, gender, body mass index (BMI), or lower limb dominance across the three groups (p > 0.05). After 4 weeks of intervention, clinical outcomes significantly improved in all three groups (p < 0.05). However, patients in the MFPH + EX group improved significantly in all outcomes compared to the MFPH and US groups (p < 0.05).ConclusionPost-treatment results showed a statistically and clinically significant improvement in pain intensity, knee ROM, and function in the MFPH group; however, combining MFPH with exercises is more beneficial in reducing KOA symptoms.Trial registrationClinical Trial Registry at (pactr.samrc.ac.za) database.NO: PACTR202311507335269. Date: November 9, 2023 (retrospectively registered).

The Role of Traditional Leaders in Local Governance: A Case Study of Jambi Province, Indonesia

Indonesia's decentralized governance system provides space for the integration of traditional leadership into local administration. This study examines the role of traditional leaders in local governance within Jambi Province, Indonesia, investigating their interactions with the formal public administration system, influence on policy implementation, and contribution to community development. This qualitative study employed a case study approach focusing on three districts in Jambi Province with varying degrees of adherence to traditional customs. Data collection involved semi-structured interviews with traditional leaders, government officials, and community members. Archival research, including local regulations and policy documents, supplemented the primary data. Thematic analysis was used to identify key themes and patterns. Traditional leaders in Jambi continue to hold significant influence in local communities, particularly in rural areas. Their roles encompass conflict resolution, cultural preservation, and advocacy for community interests. While their authority is not formally recognized within the modern administrative structure, they play a crucial role in mediating between communities and the government. The study found varying degrees of collaboration and tension between traditional leaders and government officials, depending on factors such as the leaders' individual personalities, the prevailing cultural norms of the community, and the specific policy area in question. The findings highlight the complexities of integrating traditional leadership into modern governance systems. While traditional leaders can contribute valuable local knowledge and legitimacy, their involvement can also pose challenges to bureaucratic procedures and accountability mechanisms. The study underscores the importance of recognizing and accommodating traditional authority while ensuring transparency and adherence to democratic principles.

Determination of proinflammatory cytokine levels to assess the reparative potential of tissues in ischemic damage and local correction with hyaluronic acid

The hypothesis of the study was the assumption that local correction of secondary alteration stops excessive inflammation activity and promotes early activation of reparative processes. Objective: in an animal experiment, to evaluate the dynamics in blood plasma of the concentration of circulating inflammatory cytokines in acute ischemic damage to soft tissues and after local action of a hyaluronic acid-based drug. In anesthetized Wistar rats, acute ischemic damage to the soft tissues of the thigh was simulated by mechanical compression with a vise for 7 hours. After removing the vise, the rats were divided into 2 groups of 32 individuals: control (without treatment) and experimental (3 hours after removing the vise, the drug was injected into the area bordering the compression zone with a sterile syringe based on hyaluronic acid “Hyalift-3.5”, diluted with 0.9% solution to the final concentration of the drug – 1.75%). The concentration of cytokines in blood plasma was determined, histological sections of soft tissues in the compression area were examined. An increase in the plasma concentration of proinflammatory cytokines (IL-1β, TNFα, IL-6) was revealed during the entire follow-up period (21 days), especially 7 days after the injury. To the greatest extent, these changes were observed in animals in the control group, which was manifested by a statistically significant increase in the concentration of IL-1β, TNFα and IL-6, relative to the values in intact rats: on average by 7.2; 3.7 and 5.3 times, respectively. In rats in the experimental group, local administration of a hyaluronic acid-based drug already in the early period after injury limited the severity of inflammation (an increased concentration of IL-10 was recorded in blood plasma). The sanogenetic role of local administration of hyaluronic acid in the wound process is mediated by the relief of inflammation in the early period of damage and is realized in increasing the reparative potential of tissues according to the variant of earlier and significant formation of musculoskeletal tissue regenerates.

Recent Innovations and Future Perspectives in Transferosomes for Transdermal Drug Delivery in Therapeutic and Pharmacological Applications.

There have been several non-invasive administrations that have emerged recently to replace conventional needle injections. With its minimal rejection rate, remarkable ease of administration, and remarkable patient comfort and perseverance, the transdermal drug delivery system (TDDS) is the most attractive of them all. The skincare industry, which includes cosmetics, may also find use for TDDS in addition to the pharmaceutical industry. As this strategy mainly entails local drug administration, it can prevent untargeted drug delivery to tissues not intended for the treatment and buildup of localized drug concentrations. Transdermal delivery is hampered by a number of physicochemical characteristics of the skin, which have led to a great deal of research into ways to get over these barriers. The majority of transdermal medicines that have proved effective do so by using smaller lipophilic compounds, which have a molecular weight of a few 100 Daltons. Transferosomes have proven to be an effective method for transdermal distribution of a range of therapies, including hydrophilic actives, bigger molecules, peptides, proteins, and nucleic acids, in order to get around the medications' size and lipophilicity limits. Because of their flexible form and increased surface hydrophilicity, transferosomes are essential for the delivery of medicines and other solutes through and into the skin by exploiting hydration gradients a source of energy. As a result, the medication is released into the skin layers under regulated conditions and has improved overall penetration. In this section we outline the development of transferosomes from liposomes and solid lipid nanoparticles, as well as their subsequent advancements as commercially available dosage forms, physical-chemical characteristics, and cutaneous kinetics.