Delivery Approaches Research Articles

Advances in Research of Hydrogel Microneedle-Based Delivery Systems for Disease Treatment

Microneedles (MNs), composed of multiple micron-scale needle-like structures attached to a base, offer a minimally invasive approach for transdermal drug delivery by penetrating the stratum corneum and delivering therapeutic agents directly to the epidermis or dermis. Hydrogel microneedles (HMNs) stand out among various MN types due to their excellent biocompatibility, high drug-loading capacity, and tunable drug-release properties. This review systematically examines the matrix materials and fabrication methods of HMN systems, highlighting advancements in natural and synthetic polymers, and explores their applications in treating conditions such as wound healing, hair loss, cardiovascular diseases, and cancer. Furthermore, the potential of HMNs for disease diagnostics is discussed. The review identifies key challenges, including limited mechanical strength, drug-loading efficiency, and lack of standardization, while proposing strategies to overcome these issues. With the integration of intelligent design and enhanced control over drug dosage and safety, HMNs are poised to revolutionize transdermal drug delivery and expand their applications in personalized medicine.

Enhancing COVID-19 Vaccine Efficacy: Dual Adjuvant Strategies with TLR7/8 Agonists and Glycolipids.

The controlled release of immunostimulatory agents represents a promising strategy to enhance vaccine efficacy while minimizing side effects. This study aimed to improve the efficacy of the RBD-Fc-based COVID-19 vaccine through combining of an iNKT cell agonist and a TLR7/8 agonist using covalent conjugation and temporal delivery. We hypothesized that these combinations would yield a more balanced Th1/Th2 immune response. For covalent conjugation, we employed an uncleavable linker and a self-immolative disulfide linker to conjugate α-galactosylceramide (αGC) to imidazoquinoline (IMDQ). The αGC-SS-IMDQ-Ac conjugate, designed with a prodrug strategy for controlled TLR7/8 agonist release, elicited a higher IFN-γ/IL-4 T cell response ratio than individual adjuvants or their admixture. In the temporal delivery approach, administering IMDQ followed by αGC after 2 h resulted in the highest IgG2a/IgG1 ratio, significantly surpassing other groups. A 6 h delay between glycolipid and IMDQ injections yielded balanced IgG responses, enhancing IgG, IgG1, and IgG2a levels synergistically.

Artificial Plateletoids Recruit Blood Proteins to Shield Symbiotic Thrombin: a Silk Fibroin/Calcium Interface Medicated Thrombin Generation and Preservation.

Breaking the constraints of thrombin during storage and in vivo applications remains challenging because of its low stability and sensitivity to environmental temperature and acidity. Herein, an artificial plateletoid is developed for in situ thrombin generation through a co-incubation approach with plasma in vitro, utilizing a silk fibroin/Ca2+ interface, to enhance the activity and stability of the generated thrombin. Notably, the enzymatic activity of the plateletoid thrombin platform is as high as 30Ug-1, leading to rapid clotting within 55 s, and it persisted for at least 90 days at as high as 37°C. This considerably lessens the difficulties associated with maintaining the cold chain while storing and shipping thrombin formulations. Additionally, a gastric bleeding model confirmed that the plateletoid platform improved the acid resistance of thrombin by upregulating the pH of the gastric environment (pH 0.8), facilitating oral delivery of thrombin for effective hemorrhage control in highly acidic stomach conditions. This pioneering study addresses the constraints of thrombin in storage and in vivo applications and may provide a basis for further research on biological storage and delivery approaches.

Innovative strategies and implementation science approaches for health delivery among migrants in humanitarian settings: A scoping review.

Over 100 million displaced people rely on health services in humanitarian contexts, defined as unstable or transitory settings created in response to complex emergencies. While services are often described, there is a dearth of evidence on best practices for successful implementation to guide efforts to optimize health delivery. Implementation science is a promising but underutilized tool to address this gap. This scoping review evaluates implementation science in health services for forced migrants in humanitarian settings. We conducted a scoping review according to JBI methodologies. A search of eight databases yielded 7,795 articles, after removal of duplicates, that were screened using PRISMA-ScR guidelines. Data extraction assessed study descriptors, implementation objects, barriers, facilitators, implementation strategies, and use of implementation frameworks in service delivery. Data from 116 studies represented 37 countries and 11 topic areas. Methods were mainly cross-sectional with low-medium evidence rigor. Mental health programs (25%) and vaccination services (16%) were the most common objects of implementation. Thirty-eight unique barriers were identified including resource limitations (30%), health worker shortages (24%), and security risks (24%). Among 29 facilitators, the most common were health worker availability (25%), pre-existing partnerships (25%), and positive perceptions towards the intervention (20%). More than 90% of studies collectively identified 35 implementation strategies, the most common being capacity building (44%), stakeholder engagement (35%), information dissemination (38%), and feedback mechanisms (25%). Only 10 studies used formal implementation models, with RE-AIM (n = 3) and Intervention mapping (n = 2) being most frequent. In this scoping review, we found similar barriers, facilitators, and implementation strategies across diverse humanitarian migrant settings and services. However, the use of rigorous methods and formal implementation models was rare. Frameworks included RE-AIM, CFIR, and Precede-Proceed. Increased use of implementation science frameworks and methods will help humanitarians more rigorously and systematically evaluate and develop best practices for implementation of health services for migrants in humanitarian settings.

Pathways to depressive symptoms in Chinese pregnant women and their influence on delivery approach: a qualitative comparative analysis.

The aim of this study was to apply complexity theory to explain and understand how risk factors combined in complex ways, eventually leading to a high prevalence of depressive symptoms among pregnant women. We also aimed to evaluate whether depressive symptoms affected delivery approach. The study had a longitudinal design and was conducted between May and September 2017. A total of 481 pregnant women were recruited to participate and completed closed-end surveys at two distinct times: during prenatal care at the hospital after 26 weeks of pregnancy and 1 to 4 weeks after delivery. This study identified eleven different pathways that led to an increase in depressive symptoms. Each pathway differentiated the effects of different influencing factors. Among the 481 pregnant women, 128 (26.6%) had cesarean deliveries without medical indications. Although depressive symptoms could affect delivery approach, it was not the most important factor. Surprisingly, the first production emerged as the key factor determining delivery mode. This study was innovative in that it examined which factors and which combinations of factors were necessary for the development of depressive symptoms. Additionally, this study provided a better understanding of the mechanisms underlying the choice of cesarean section without medical indications.

Intranasal Route an Alternative Approach for Systemic Drug Delivery: Recent Strategies and Progression

: Intranasal administration has proven to be a viable alternative for local and systemic delivery of varied therapeutic agents. This route has been potentially researched for delivering polar compounds, vaccines, hormones, peptides, proteins, etc. Being non-invasive and painless with a fast onset of action (both local and systemic), intranasal has become an ideal route for medication to children. This route is specifically employed for the delivery of drugs that are unstable in GIT, which gets significantly degraded or metabolized by the first-pass effect. The nasal route's high absorption and permeability profile has led to its exploration as a substitute for parenteral delivery. This paper reviews the feasibility and potentials of intranasal administration, discussing its benefits, drawbacks, market analysis, factors affecting nasal drug delivery system, conventional and novel strategies (polymeric and nano-carrier-based delivery systems) to improve nasal ab-sorption and its clinical management of varied systemic and topical disorders viz. neurodegenerative, pulmonary, microbial, neoplastic, etc.

Mastoid approach for local drug delivery to the inner ear for treating hearing loss

Hearing loss is a prevalent disability worldwide. Dexamethasone (Dex) is commonly used to treat hearing loss, administered either systemically or locally. However, targeted delivery of Dex to the inner ear remains challenging, which limits its therapeutic efficacy. This study aimed to develop new methods to improve Dex delivery to the inner ear and enhance its treatment effect. Mastoid, intraperitoneal, and intratympanic delivery routes for Dex were investigated in guinea pig cochlea. Liquid chromatography-mass spectrometry and immunohistochemistry were employed to compare the distribution of Dex in the perilymph and tissue uptake. Poly (lactic-co-glycolic acid) nanoparticles loaded with Dex (PLGA-NPs-Dex) were prepared, and their transport mechanism across the round window membrane (RWM) was explored. Among the three delivery routes, mastoid administration produced the highest Dex concentration in the perilymph. Compared to the control, PLGA-NPs-Dex provided significantly enhanced protection against lipopolysaccharide- and noise-induced hearing damage following mastoid administration. Mastoid delivery provides an accessible route for drug delivery to the inner ear and nanoparticle-based systems via this route represent a viable strategy for treating inner ear diseases. This approach caused less damage to the inner ear, making it a promising option for clinical use in treating hearing loss.

Combining ultrasound technology with targeted fucoidan/arginine-gelatin nanoparticles loaded with doxorubicin to enhance therapeutic efficacy and modulate bioeffects in drug-resistant triple-negative breast cancer.

Triple-negative breast cancer (TNBC) presents formidable challenges due to its aggressive nature and high recurrence rates, compounded by the involvement of epithelial-mesenchymal transition (EMT) in its progression and metastasis. Standard chemotherapy, which typically employs doxorubicin (DOX), remains a primary treatment approach. However, multidrug resistance (MDR) mechanisms, which include ATP-binding cassette transporters and EMT, contribute to treatment failures. Ultrasound has emerged as a promising modality among the various strategies explored to address MDR in TNBC. It serves as a diagnostic tool and holds therapeutic potential by inducing various biological effects depending on the exposure level. Targeted nanoparticles offer a means to enhance drug delivery efficiency. Our study aims to advance ultrasound technology combined with biocompatible nanoparticles using simplified preparation methods to improve treatment outcomes for drug-resistant TNBC. In particular, employing DOX-loaded fucoidan/arginine-gelatin nanoparticles facilitated the targeted delivery of chemotherapy drugs to tumors by effectively interacting with P-selectin, resulting in tumor growth inhibition. Furthermore, these nanoparticles mitigated MDR and EMT, particularly when combined with ultrasound treatment. This integrated approach of nanoparticle delivery with ultrasonography opens up a promising and innovative avenue for clinical cancer research.

Enhancing retention and permeation of rapamycin for osteoarthritis therapy using a two-stage drug delivery system

Osteoarthritis (OA) remains a challenging degenerative joint disease, largely associated with chondrocyte apoptosis during its development. Preserving chondrocytes stands as a promising strategy for OA treatment. Rapamycin (RP) exhibits chondrocyte protection by fostering autophagy. Nevertheless, the swift clearance of intra-articular injections and the dense cartilage extracellular matrix (ECM) hinder RP from effectively reaching chondrocytes. Herein, we developed a "two-stage" drug delivery system (RP@PEG-PA@P-Lipo). This system comprises primary nanoparticles (P-Lipo), liposomes modified with a collagen II targeting peptide (WYRGRLC), and secondary nanoparticles (RP@PEG-PA), PEG-modified PAMAM encapsulating rapamycin (RP). RP@PEG-PA@P-Lipo demonstrates adherence to the cartilage surface with WYRGRLC, substantially prolonging retention within the joint cavity. Subsequently, released RP@PEG-PA can effectively penetrate the cartilage and deliver RP to chondrocytes through small size and charge-driven forces. In vitro and in vivo experiments corroborate its notable therapeutic effects on OA. This study holds promise in offering a novel approach for clinical drug delivery and OA treatment.

From Conventional to Cutting-edge: A Comprehensive Review on Drug Delivery Systems

: The essential need for efficacious conveyance of therapeutics to specific tissues or cells, refinement of drug formulations, and the scalability of industrial production drives the pre-sent-day demand for enhanced drug delivery systems (DDS). Newly devised drugs often exhibit suboptimal biopharmaceutical properties, resulting in diminished patient adherence and adverse side effects. The paramount importance of site-specific drug delivery lies in its capacity to facili-tate the targeted administration of diverse therapeutic agents, catering to both localized ailments and systemic treatments. Alongside targeted drug delivery strategies encompassing ligand-based targeting and stimuli-responsive systems, the advent of cutting-edge nanotechnologies such as nanoparticles, liposomes, and micelles has marked a paradigm shift. Additionally, personalized medicines have emerged as a consequential facet of drug delivery, emphasizing the customization of treatment approaches. Researchers have explored an excess of methodologies in the advance-ment of these formulation technologies, including stimuli-responsive drug delivery, 3D printing, gene delivery, and various other innovative approaches. This comprehensive review aims to pro-vide a holistic understanding of the past, present, and future of drug delivery systems, offering in-sights into the transformative potential of emerging technologies.

Nanotechnology: Current Developments, Applications and Patents for Non-invasive Topical Cosmetics and Dermatological Therapeutic Delivery

: Nanotechnology exhibits the advancement in the field of invention, by improving the potency of the formulation through the delivery of inventive solutions. To resolve several limita-tions related to conventional formulations, nanotechnology applications are increasing in the cosmetics and dermatological area. Cosmetic and dermatological preparations are considered a thriving branch of the body care arena and their usage has increased dramatically through the past years. Scientists are designing innovative delivery mechanisms and emerging innovations that are presently being utilized in the development of cosmetics. Inventive nanocarriers such as nio-somes, liposomes, microemulsions, nanoemulsions, solid-lipid nanoparticles, nanospheres, and nanostructured (lipid) carriers have substituted the use of traditional drug delivery. These innova-tive nanocarriers have the convenience of better skin permeation, sustained and controlled drug delivery, precise location, higher stability, and greater incorporated capability. Since the usage of cosmetics has increased, the usual delivery system has been substituted by modern delivery ap-proaches. The introduction of newer advancements and novel drug delivery systems make cos-metics and cosmeceuticals more popular with increased market share. This review article on nan-otechnology employed in cosmetics and dermatology emphasizes the numerous innovative nanocarriers designed for cosmetic and dermatologic drug delivery, their negative and positive aspects, and their toxicity.

Self-assembled sustainable bionanocomposite hydrogels from chitosan for the combination chemotherapy of hydrophobic and hydrophilic drugs.

Self-assembled hydrogels derived from naturally sourced polymers have gained significant interest in drug delivery applications, owing to their potential, exceptional biocompatibility and sustainable properties. This work presents the development and application of self-assembled nanocomposite hydrogels from chitosan and nanosilver as a pH responsive drug delivery system for the controlled release of doxorubicin and paclitaxel in anticancer therapy. Chitosan was functionalized with 4-formyl benzoic acid for incorporating both hydrophobic and hydrophilic anticancer drugs. The self-assembled nanocomposite hydrogels formed from chitosan and 4-formyl benzoic acid by various non-covalent interactions were studied by FT-IR, Dynamic Light Scattering (DLS), and rheology analysis. Rheology studies demonstrated the hydrogel's shear-thinning nature, enabling easy injection. The antibacterial activity can be evidenced by agar-well diffusion assay and MIC values were measured. The antibacterial effect was analyzed by agar-well diffusion assays and H2-DCFDA assay, providing a comprehensive understanding. In-vivo pharmacokinetic studies on Wistar rats demonstrated promising and effective systemic circulation of drug loaded material in blood, thus supporting its potential for therapeutic applications. All these studies and results demonstrates feasibility and a novel synergistic dual drug delivery approach, promising the synergy between hydrophobic paclitaxel (PTX) and hydrophilic Doxorubicin hydrochloride (Dox.HCl), for improved anticancer efficacy.

Current Advancements on Oral Protein and Peptide Drug Delivery Approaches to Bioavailability: Extensive Review on Patents.

Protein and peptide-based drugs have greater therapeutic efficacy and potential application and lower toxicity compared to chemical entities in long-term use within optimum concentration as they are easily biodegradable due to biological origin. While oral administration is preferable, most of these substances are currently administered intravenously or subcutaneously. This is primarily due to the breakdown and poor absorption in the GI tract. Hence, ongoing research is focused on investigating absorption enhancers, enzyme inhibitors, carrier systems, and stability enhancers as potential strategies to facilitate the oral administration of proteins and peptides. Investigations have been directed towards advancing novel technologies to address gastrointestinal (GI) barriers associated with protein and peptide medications. The current review intensifies formulation and stability approaches for oral protein & peptide drug delivery systems with all significant parameters intended for patient safety. Notably, certain innovative technologies have been patented and are currently undergoing clinical trials or have already been introduced into the market. All the approaches stated for the administration of protein and peptide drugs are critically discussed, having their current status, future directions, and recent patents published in the last decades.

The heterogeneity among people re-engaging in antiretroviral therapy highlights the need for a differentiated approach: results from a cross-sectional study in Johannesburg, South Africa.

Disengagement and re-engagement with antiretroviral therapy (ART) are common in South Africa, but routine monitoring is insufficient to inform policy development. To address this gap, Anova implemented the 2020 National Adherence Guidelines' re-engagement standard operating procedure (re-engagement SOP) and collected additional data to describe the characteristics of re-engagement visits to inform HIV programmes. Between July and December 2022, we conducted a study at nine primary healthcare facilities in Johannesburg. Staff were trained on the re-engagement SOP and provided with job aides to support implementation. Administration clerks categorized visits based on the time elapsed since the missed appointment: ≤14days and >14 days, with the latter identified as re-engaging. For these clients, clinicians filled out "re-engagement clinical assessment forms" that included visit dates, both clinician-assessed and self-reported treatment interruptions, and clinical details. Data on missed appointments and previous viral loads were extracted from medical records. The information was entered into REDCap. We present data from three out of the nine facilities, selected for their comprehensive data collection and high coverage of all re-engaging clients. A total of 2342 clients returned following a missed scheduled appointment. The majority, 1523 (65%), missed their appointments by ≤ 14 days, while 819 (35%) were >14 days late (re-engaging). Among those re-engaging, 635 (78%) re-engagement clinical assessment forms were completed. A missed appointment date was available for 623 with 25% (n = 161) returning 2-4 weeks late, 47% (n = 298) 4-12 weeks and 26% (n = 164) >12 weeks late. Self-reported ART interruption, available for 89% (567/635), indicated the majority (54%, n = 304) experienced no interruption. Clinical concerns were identified in 65 (10%) cases. A majority (79%, 504/635) had prior viral load results, with 73% (370/504) below 50 copies/ml. Clients frequently return to care shortly after missed appointments. Despite missing scheduled ART refill dates, many report not interrupting treatment, either having treatment on hand or sourcing ART elsewhere. Most re-engaging clients were adherent prior to disengagement, and clinical concerns are rare. A differentiated service delivery approach, prioritizing flexibility and reduced healthcare burden, is required to support client's needs and preferences at re-engagement.

Dextran-based Drug Delivery Approaches for Lung Diseases: A Review.

Respiratory disorders, such as tuberculosis, cystic fibrosis, chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary inflammation, are among the most prevalent ailments in today's world. Dextran, an exopolysaccharide formed by Leuconostoc mesenteroides (slimeproducing bacteria), and its derivatives are investigated for several therapeutic utilities. Dextranbased drug delivery system can become an innovative strategy in the treatment of several respiratory ailments as it offers numerous advantages, such as mucolytic action, airway hydration, antiinflammatory properties, and radioprotective effect as compared to other polysaccharides. Being biocompatible, flexible hydrophilic nature, biodegradable, tasteless, odourless, non-mutagenic, watersoluble and non-toxic edible polymer, dextran-based drug delivery systems have been explored for a wide range of therapeutic applications, especially in lungs and respiratory diseases. The present article comprehensively discusses various derivatives of dextran with their attributes to be considered for drug delivery and extensive therapeutic benefits, with a special emphasis on the armamentarium of dextran-based formulations for the treatment of respiratory disorders and associated pathological conditions. The information provided will act as a platform for formulation scientists as important considerations in designing therapeutic approaches for lung and respiratory diseases. With an emphasis on lung illnesses, this article will offer an in-depth understanding of dextran-based delivery systems in respiratory illnesses.

MiRNAs in HCC, pathogenesis, and targets.

Liver cancer is the third leading cause of cancer-related mortality worldwide. Hepatocellular carcinoma (HCC), the most common type of primary liver cancer is driven by complex genetic, epigenetic, and environmental factors. MicroRNAs, a class of naturally-occurring small non-coding RNAs play crucial roles in HCC by simultaneously modulating expression of multiple genes in a fine-tuning manner. Significant progress has been made in understanding how miRNAs influence key oncogenic pathways, including cell proliferation, apoptosis, angiogenesis, and epithelial-mesenchymal transition (EMT), as well as their role in modulating the immune microenvironment in HCC. Due to the unexpected stability of miRNAs in the blood and fixed HCC tumors, recent advancements also highlight their potential as non-invasive diagnostic tools. Restoring or inhibiting specific miRNAs have offered promising strategies for targeted HCC treatment by suppressing malignant hepatocyte growth and enhancing antitumor immunity. In this comprehensive review, we consolidate previous research and provide the latest insights into how miRNAs regulate HCC and their therapeutic and diagnostic potential. We delve into dysregulation of miRNA biogenesis in HCC, the roles of miRNAs in proliferation and apoptosis of malignant hepatocytes, angiogenesis and metastasis of HCC, immune microenvironment in HCC and drug resistance. We also discuss the therapeutic and diagnostic potential of miRNAs and delivery approaches of miRNA drugs to overcome the limitations of current HCC treatment options. By thoroughly summarizing the roles of miRNAs in HCC, our goal is to advance the development of effective therapeutic drugs with minimal adverse effects and to establish precise tools for early diagnosis of HCC.

Plant-mediated gold nanoparticles in cancer therapy: exploring anti-cancer mechanisms, drug delivery applications, and future prospects

Gold nanoparticles (AuNPs) exhibit great promise in cancer therapy and drug delivery due to their unique physicochemical properties. The utilization of plant extracts and phytochemicals for the synthesis of AuNPs offers a simple, rapid, eco-friendly, and cost-effective alternative. This review provides an in-depth analysis of the role of plant-mediated AuNPs in cancer treatment, focusing on their core mechanisms, drug delivery applications, and future potential. It emphasizes the advantages of green synthesis methods for cancer therapy, detailing the processes involved and highlighting various plants used for nanoparticle biosynthesis. The review also explores the anti-cancer effects of plant-mediated AuNPs, such as their ability to selectively target cancer cells and induce apoptosis, supported by both in vitro and in vivo studies. Additionally, the application of these nanoparticles in targeted drug delivery for cancer therapy is examined. The review addresses biocompatibility and toxicity concerns, providing insights into the safety of these nanoparticles. Future research directions and challenges are discussed to overcome current limitations and maximize their clinical applicability. In summary, plant-mediated AuNPs offer a sustainable and effective approach for cancer therapy and drug delivery, with their green synthesis and diverse anti-cancer properties highlighting their potential. Further research is essential to fully realize their clinical benefits.

Perception and Belief of Dietary Intake among Newly Diagnosed with Gynaecologic Cancer in Malaysia: A Qualitative Study

Background: Gynaecologic cancers (GC) experience unintentional weight loss and inadequate oral intake even before treatment. Cancer patients are at risk of accessing inaccurate advice and misleading information due to the prevalence of misinformation regarding nutrition and cancer in the media. This study aimed to obtain a comprehensive understanding of the perception and belief of dietary intake among newly diagnosed with GC in Malaysia. Methods: We conducted in-depth qualitative interviews with 12 GC respondents from three major ethnicities and continued until the saturation point was reached. A semi-structured interview guide is employed. The interviews were audio recorded and verbally transcribed. Thematic analysis with theoretical saturation was applied to data analysis. Results: The majority of patients interviewed reported that they made dietary modifications following their GC diagnosis, such as healthy eating, and began taking supplements. Their belief and perception of dietary intake were influenced by the impact of diagnosis, uncertainty, and fear of cancer progression and empowerment through nutrition. The cultural influence and access to resources and information might affect their dietary intake. There was evidence of navigating information overload from various sources after newly diagnosed GC. They felt a dilemma in food choices, balancing emotional and nutritional needs. The multidisciplinary support systems and healthcare delivery approach were useful. Discussion and conclusion: The perception and belief of dietary intake among newly diagnosed with GC in Malaysia is diverse and can vary greatly depending on individual experiences, beliefs, and situations. They may attempt to restore some control over their health in the face of a cancer diagnosis. All respondents admitted that they changed to a healthy diet after being diagnosed with GC. The healthcare profession might benefit from current qualitative research to better understand more patients and increase the quality of oncology dietetic service and decision-making. Hence, effective dietary interventions and support strategies could be established for this population.

The Application of Nano Drug Delivery Systems in Female Upper Genital Tract Disorders.

The prevalence of female reproductive system disorders is increasing, especially among women of reproductive age, significantly impacting their quality of life and overall health. Managing these diseases effectively is challenging due to the complex nature of the female reproductive system, characterized by dynamic physiological environments and intricate anatomical structures. Innovative drug delivery approaches are necessary to facilitate the precise regulation and manipulation of biological tissues. Nanotechnology is increasingly considered to manage reproductive system disorders, for example, nanomaterial imaging allows for early detection and enhances diagnostic precision to determine disease severity and progression. Additionally, nano drug delivery systems are gaining attention for their ability to target the reproductive system successfully, thereby increasing therapeutic efficacy and decreasing side effects. This comprehensive review outlines the anatomy of the female upper genital tract by highlighting the complex mucosal barriers and their impact on systemic and local drug delivery. Advances in nano drug delivery are described for their sustainable therapeutic action and increased biocompatibility to highlight the potential of nano drug delivery strategies in managing female upper genital tract disorders.

Solid-State Nanopores for Spatially Resolved Chemical Neuromodulation.

Most neural prosthetic devices are based on electrical stimulation, although the modulation of neuronal activity by a localized chemical delivery would better mimic physiological synaptic machinery. In the past decade, various drug delivery approaches attempted to emulate synaptic transmission, although they were hampered by poor retention of their cargo while reaching the target destination, low spatial resolution, and poor biocompatibility and stability of the materials involved. Here, we propose a planar solid-state device for multisite neurotransmitter translocation at the nanoscale consisting of a nanopatterned ceramic membrane connected to a reservoir designed to store neurotransmitters. We achieved diffusion-mediated glutamate stimulation of primary neurons, while we showed the feasibility to translocate other molecules through the pores by either pressure or diffusion, proving the versatility of the proposed technology. Finally, the system proved to be a promising neuronal stimulation interface in mice and nonhuman primates ex vivo, paving the way toward a biomimetic chemical stimulation in neural prosthetics and brain machine interfaces.