Local Delivery Methods Research Articles

The combination of hydrogels and rutin-loaded black phosphorus nanosheets treats rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by inflammation, joint pain, and cartilage degradation. The fluctuating nature of RA often necessitates long-term oral administration of treatment drugs, which can unfortunately lead to adverse effects such as gastrointestinal discomfort and hepatic and renal dysfunction. Therefore, a percutaneous local delivery method for the release of inflammatory modulators in arthritic joints represents a promising therapeutic approach for RA. In this study, we have developed a unique and innovative therapeutic platform (named BP-Rut@Gel). This hydrogel was formulated by incorporating the drug Rutin (Rut) into Black phosphorus nanosheets (BP) and subsequently integrating them within a Hyaluronic Acid (HA) and Polyvinyl Alcohol (PVA) matrix to create a composite hydrogel. Notably, Secondly, photothermal therapy (PTT) under Near-Infrared Irradiation (NIR) and anti-inflammatory drugs synergistically worked together to efficiently quell inflammation and enhance therapeutic effectiveness. Additionally, toxicity experiments have revealed that our synthesized black phosphorus nanosheet composite hydrogel possesses excellent biocompatibility and significantly reduces the inflammatory response in RA joints. Given these remarkable properties, our BP-Rut@Gel hydrogel held significant promise and demonstrated immense clinical potential for the treatment of RA.

Nanoparticle-mediated delivery of placental gene therapy via uterine artery catheterization in a pregnant rhesus macaque

Nanoparticles offer promise as a mechanism to non-invasively deliver targeted placental therapeutics. Our previous studies utilizing intraplacental administration demonstrate efficient nanoparticle uptake into placental trophoblast cells and overexpression of human IGF1 (hIGF1). Nanoparticle-mediated placental overexpression of hIGF1 in small animal models of placental insufficiency and fetal growth restriction improved nutrient transport and restored fetal growth. The objective of this pilot study was to extend these studies to the pregnant nonhuman primate and develop a method for local delivery of nanoparticles to the placenta via maternal blood flow from the uterine artery. Nanoparticles containing hIGF1 plasmid driven by the placenta-specific PLAC1 promoter were delivered to a mid-gestation pregnant rhesus macaque via a catheterization approach that is clinically used for uterine artery embolization. Maternal-fetal interface, fetal and maternal tissues were collected four days post-treatment to evaluate the efficacy of hIGF1 treatment in the placenta. The uterine artery catheterization procedure and nanoparticle treatment was well tolerated by the dam and fetus through the four-day study period following catheterization. Nanoparticles were taken up by the placenta from maternal blood as plasmid-specific hIGF1 expression was detected in multiple regions of the placenta via in situ hybridization and qPCR. The uterine artery catheterization approach enabled successful delivery of nanoparticles to maternal circulation in close proximity to the placenta with no concerns to maternal or fetal health in this short-term feasibility study. In the future, this delivery approach can be used for preclinical evaluation of the long-term safety and efficacy of nanoparticle-mediated placental therapies in a rhesus macaque model.

Probiotics, tetracycline fibres and chlorhexidine gel's effectiveness in treating chronic periodontitis as a supplement to scaling and root planning.

A periodontal pocket can result into progressive loss of attachment. Many agents are tried to improve periodontal health. Hence this research was done to estimate the effectiveness of Tetracycline fibers; Probiotics and Chlorhexidine gel as a conjunction to scaling and root planning (SRP) in the treatment of chronic periodontitis. In all, 60 patients between the ages of 25 and 35 who had generalized chronic periodontitis and had a probing pocket depth (PPD) of at least 5 mm were enrolled for this study. Four groups of 15 patients each were created from the patients: Group 1: Tetracycline fibres after SRP, Group 2: Chlorhexidine gel, Group 3: Probiotic mouthwash and Group 4: Rinse with regular saline. At baseline, oral prophylaxis was administered to all groups. Gingival index (GI), Plaque index (PI), and probing depth (PD), among other clinical indicators, were evaluated at baseline, two weeks, and four weeks, respectively. All clinical findings, along withPlaque index (PI), Gingival index (GI), and Probing depth at various time intervals, decreased statistically significantly. Tetracycline fibres, Chlorhexidine gel, and probiotic mouthwash are all similarly effective for treating chronic periodontitis, but they are all more effective than SRP alone, according to an intergroup comparison. When it comes to SRP, local medication delivery methods are beneficial in treating periodontitis.

Enhancing Outcomes in Prosthetic Joint Infections: The Significance of the Periprosthetic Joint Infection Tumor, Node, and Metastasis (PJI-TNM) Classification and Biodegradable Antibiotic Beads.

Periprosthetic joint infections (PJIs) that occur after hip and knee arthroplasty have a major influence on patient outcomes and healthcare expenses. This study assesses the effectiveness of the PJI tumor, node, and metastasis (PJI-TNM) categorization system and the latest developments in local antibiotic delivery methods for the treatment of PJIs. The study involved a retrospective analysis of 23 patients who received treatment for septic hip or knee prostheses at the SUUB Orthopedics and Traumatology Clinic between January 1, 2022, and February 10, 2024. Approval was gained following ethical considerations. Patients were categorized using the PJI-TNM system, and their therapy was customized based on the severity of the infection. The surgical procedures involved either one-stage or two-stage revisions, utilizing vancomycin and gentamicin antibiotic-loaded calcium sulfate beads to administer antibiotics locally. Data pertaining to demographics, clinical characteristics, and microbiology were gathered and examined. The study comprised 14 male and 9 female patients, with an average age of 68 years. The presence of chronic infections was mostly seen, indicating the development of mature biofilm. Prevalent coexisting medical conditions included diabetes, obesity, and heart failure. The duration of infection control measures was, on average, six months, and 65% of patients reported experiencing enhanced mobility. Acute infections with positive antibiotic responses underwent one-stage modifications. For the majority of patients, a treatment approach involving two-stage modifications, which includes the use of antibiotic-loaded spacers followed by the installation of a prosthesis, proved to be beneficial. The PJI-TNM classification system improves the management of PJI by offering a systematic method for customized therapy. Calcium sulfate beads, which are biodegradable carriers for antibiotics, provide notable advantages, especially for individuals with severe comorbidities. Continuous progress in diagnostic techniques and localized administration of antibiotics is essential for enhancing the therapy of PJI and improving patient outcomes.

Novel Collagen Membrane Formulations with Irinotecan or Minocycline for Potential Application in Brain Cancer.

Our study explores the development of collagen membranes with integrated minocycline or irinotecan, targeting applications in tissue engineering and drug delivery systems. Type I collagen, extracted from bovine skin using advanced fibril-forming technology, was crosslinked with glutaraldehyde to create membranes. These membranes incorporated minocycline, an antibiotic, or irinotecan, a chemotherapeutic agent, in various concentrations. The membranes, varying in drug concentration, were studied by water absorption and enzymatic degradation tests, demonstrating a degree of permeability. We emphasize the advantages of local drug delivery for treating high-grade gliomas, highlighting the targeted approach's efficacy in reducing systemic adverse effects and enhancing drug bioavailability at the tumor site. The utilization of collagen membranes is proposed as a viable method for local drug delivery. Irinotecan's mechanism, a topoisomerase I inhibitor, and minocycline's broad antibacterial spectrum and inhibition of glial cell-induced membrane degradation are discussed. We critically examine the challenges posed by the systemic administration of chemotherapeutic agents, mainly due to the blood-brain barrier's restrictive nature, advocating for local delivery methods as a more effective alternative for glioblastoma treatment. These local delivery strategies, including collagen membranes, are posited as significant advancements in enhancing therapeutic outcomes for glioblastoma patients.

Effectiveness of antibiotic-coated intramedullary nails for open tibia fracture infection prevention. A systematic review and meta-analysis

IntroductionOpen Tibia fractures are associated with high rates of Fracture Related Infection (FRI). Given the negative outcomes and increased costs related to the latter, several prophylactic local antibiotic delivery methods have been proposed, aiming to decrease the FRI rate. Our objective with this study was to determine the effectiveness of antibiotic-coated intramedullary nails for open tibia FRI prevention. Patients and MethodsWe conducted a PRISMA compliant systematic review and meta-analysis. Queries were performed on Embase, PubMed, Lilacs and Cochrane data libraries. Seventeen studies were included for qualitative analysis and 2 studies were amenable for meta-analysis. ResultsGlobal infection, deep infection and non-union rates were 8.4%, 5.4% and 3.7% in the antibiotic-coated nail group and 22%, 14% and 14% in the non-antibiotic-coated nail group respectively. The meta-analysis showed a protective trend that favored the antibiotic-coated nail group although it didn't achieve statistical significance: deep infection Relative Risk (RR) (RR = 0.17 CI95% [0.02 – 1.31]); global infection RR = 0.36 CI95% [0.10 – 1.35]) and non-union (RR = 0.14 CI95% [0.02 – 1.22]), ConclusionsOur findings suggest a favorable trend towards antibiotic-coated nail, with decreased risk of global infection, deep infection and non-union as compared to non-antibiotic-coated nail in patients with open tibia fractures. Nonetheless, higher level evidence studies are required to confirm our findings.

The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF): feasibility trial protocol.

Topical lidocaine patches, applied over rib fractures, have been suggested as a non-invasive method of local anaesthetic delivery to improve respiratory function, reduce opioid consumption and consequently reduce pulmonary complications. Older patients may gain most benefit from improved analgesic regimens yet lidocaine patches are untested as an early intervention in the Emergency Department (ED). The aim of this trial is to investigate uncertainties around trial design and conduct, to establish whether a definitive randomised trial of topical lidocaine patches in older patients with rib fractures is feasible. RELIEF is an open label, multicentre, parallel group, individually randomised, feasibility randomised controlled trial with economic scoping and nested qualitative study. Patients aged ≥ 65 years presenting to the ED with traumatic rib fracture(s) requiring admission will be randomised 1:1 to lidocaine patches (intervention), in addition to standard clinical management, or standard clinical management alone. Lidocaine patches will be applied immediately after diagnosis in ED and continued daily for 72 hours or until discharge. Feasibility outcomes will focus on recruitment, adherence and follow-up data with a total sample size of 100. Clinical outcomes, such as 30-day pulmonary complications, and resource use will be collected to understand feasibility of data collection. Qualitative interviews will explore details of the trial design, trial acceptability and recruitment processes. An evaluation of the feasibility of measuring health economics outcomes data will be completed. Interventions to improve outcomes in elderly patients with rib fractures are urgently required. This feasibility trial will test a novel early intervention which has the potential of fulfilling this unmet need. The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF) feasibility trial will determine whether a definitive trial is feasible. ISRCTN14813929 (22/04/2021).

Triptolide nanoemulsion gel as a transdermal drug delivery system: preparation, pharmacokinetics, and rheumatoid arthritis evaluation.

This study aimed to develop and evaluate triptolide nanoemulsion gels (TP-NE gels) as a transdermal drug delivery system. TP-NE was prepared and optimized via emulsification and the central composite design response surface method. The optimized TP-NE gel was evaluated in vitro and in vivo. TP-NE gel microstructure, in vitro and in vivo pharmacokinetics, and anti-rheumatoid arthritis effects were studied to evaluate the feasibility of its percutaneous administration. The Optimized TP-NE was observed using a Malvern Autosizer Nano ZS 90 inspection system and a transmission electron microscope (TEM). The nanoemulsion had an average size of 162.9 ± 0.281 nm, a polydispersity index of 0.272 ± 0.024, a zeta potential of -30.03 ± 2.01 mV, and mostly spherical and uniform morphology. In addition, the TP-NE gel pharmacokinetics, assessed via a skin-blood two-site synchronous microdialysis, revealed that TP was higher in the skin than in the blood. TP-NE gel is crucial in reducing knee edema, inhibiting inflammation, and treating rheumatoid arthritis by regulating tumor necrosis factor-alpha, interleukin-1β, and -6 levels. The TP-NE gel is a promising local delivery method for rheumatoid arthritis (RA)-associated edema and inflammation and can serve as a prospective platform for percutaneous TP administration.

The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF): feasibility trial protocol

Background: Topical lidocaine patches, applied over rib fractures, have been suggested as a non-invasive method of local anaesthetic delivery to improve respiratory function, reduce opioid consumption and consequently reduce pulmonary complications. Older patients may gain most benefit from improved analgesic regimens yet lidocaine patches are untested as an early intervention in the Emergency Department (ED). The aim of this trial is to investigate uncertainties around trial design and conduct, to establish whether a definitive randomised trial of topical lidocaine patches in older patients with rib fractures is feasible. Methods: RELIEF is an open label, multicentre, parallel group, individually randomised, feasibility randomised controlled trial with economic scoping and nested qualitative study. Patients aged ≥ 65 years presenting to the ED with traumatic rib fracture(s) requiring admission will be randomised 1:1 to lidocaine patches (intervention), in addition to standard clinical management, or standard clinical management alone. Lidocaine patches will be applied immediately after diagnosis in ED and continued daily for 72 hours or until discharge. Feasibility outcomes will focus on recruitment, adherence and follow-up data with a total sample size of 100. Clinical outcomes, such as 30-day pulmonary complications, and resource use will be collected to understand feasibility of data collection. Qualitative interviews will explore details of the trial design, trial acceptability and recruitment processes. An evaluation of the feasibility of measuring health economics outcomes data will be completed. Discussion: Interventions to improve outcomes in elderly patients with rib fractures are urgently required. This feasibility trial will test a novel early intervention which has the potential of fulfilling this unmet need. The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF) feasibility trial will determine whether a definitive trial is feasible. ISRCTN Registration: ISRCTN14813929 (22/04/2021).

Novel Nanoaggregates from Phoenix dactylifera (date palm) for Inhalational Management of Cystic Fibrosis Using Dry Powder Inhalers

PurposePhoenixdactylifera extracts have shown efficacy as antioxidants and antibacterials for the treatment of lung diseases; however, the choice of route of administration remains a problem. The use of natural antibacterial remedies for the management of cystic fibrosis (CF) is promising due to recurring bacterial resistance to current antibiotics. Dry powder inhalers (DPIs) have also been identified as a patient-friendly, noninvasive method for local delivery of drugs to the lungs. Therefore, this work, which is the first of its kind, aimed to formulate nanoparticles of date palm extracts as DPIs and evaluate their aerodynamic and antibacterial biofilm characteristics for the potential treatment of CF.MethodChitosan-based nanoparticles (CDN) comprising aqueous date fruit extract with increasing concentrations of chitosan (0.05, 0.1, and 0.2% w/v) were prepared. The in vitro aerosolization of the formulations was studied using a next-generation impactor (NGI), and good aerosolization profiles were achieved. The produced nanoparticles were characterized using FTIR and XRD to confirm physical properties and TEM and zeta sizer to confirm shape and size. The antimicrobial activity of CDN was evaluated using a Pseudomonas aeruginosa biofilm model cultured in an artificial sputum medium (ASM) mimicking cystic fibrosis conditions in the lungs.ResultsNanoparticles containing 0.05% w/v chitosan demonstrated the highest encapsulation efficiency (55.91%) and delivered the highest emitted dose (98.92%) and fine particle fraction (42.62%). CDN demonstrated the first-time-ever reported significant 3.3 log-cycle inhibition of P. aeruginosa biofilm cultured in ASM. TEM images revealed the formation of spherical particles with an average size of 42.98 ± 19.19 nm. FTIR and XRD studies demonstrated the compatibility of the components with the presence of the characteristic features of chitosan and date powder.ConclusionsThis novel work showcases CDN as a prophylactic adjuvant for the management of cystic fibrosis using DPI.

Synthesis and characterization of ciprofloxacin-loaded biodegradable magnesium implants for the prevention of implant-associated infections

Thanks to developments in prophylactic antibiotics in recent decades, the risk of wound infection in orthopedic surgeries decreased significantly. Different local antibiotic delivery methods are employed to reduce hard and soft tissue-related infection. This research is aimed at studying the efficacy of a brand-new biodegradable, ciprofloxacin (CP)-loaded with various amounts of Gelatin (GE) (5 and 10 wt%), sealed the pores and cracks of magnesium oxide - titanium dioxide (MgO–TiO2) nanocomposite film fabricated by Micro-Arc Oxidation (MAO) process on the surface of pure Mg implant. The results indicated that both synthesized GE-CP coatings on the surface of MgO–TiO2 films are biocompatible and antibacterial (with rate of 99.99%) although the corrosion resistance of the coating containing 10 wt% of GE is more than doubled that of the composite coating comprising 5 wt% of GE, and the release of CP from MgO–TiO2/10 GE-CP coating was more slowly. It can be, therefore, concluded that magnesium (Mg) implants with this composite coating containing 10 wt% of GE could be potentially used for bone regeneration applications.

Local Drug Delivery Strategies towards Wound Healing.

A particular biological process known as wound healing is connected to the overall phenomena of growth and tissue regeneration. Several cellular and matrix elements work together to restore the integrity of injured tissue. The goal of the present review paper focused on the physiology of wound healing, medications used to treat wound healing, and local drug delivery systems for possible skin wound therapy. The capacity of the skin to heal a wound is the result of a highly intricate process that involves several different processes, such as vascular response, blood coagulation, fibrin network creation, re-epithelialisation, collagen maturation, and connective tissue remodelling. Wound healing may be controlled with topical antiseptics, topical antibiotics, herbal remedies, and cellular initiators. In order to effectively eradicate infections and shorten the healing process, contemporary antimicrobial treatments that include antibiotics or antiseptics must be investigated. A variety of delivery systems were described, including innovative delivery systems, hydrogels, microspheres, gold and silver nanoparticles, vesicles, emulsifying systems, nanofibres, artificial dressings, three-dimensional printed skin replacements, dendrimers and carbon nanotubes. It may be inferred that enhanced local delivery methods might be used to provide wound healing agents for faster healing of skin wounds.

Local Government Responses to State Fiscal Controls: The Effects of Fiscal Preemptions on the Methods of Local Service Delivery

This study aims to investigate how local governments strategically respond to fiscal controls imposed by state governments. Specifically, we explore the effects of state fiscal preemptions on the way local governments deliver public services—that is, contracting out. Using negative binomial regressions, we found that state fiscal preemptions increase the tendency of local governments to contract out public services. However, the dynamics of contracting out depend on the local government’s current municipal fiscal status and the type of service provider. When local governments perceive a high level of fiscal stress, they tend to take a passive stance to contracting out. Moreover, the relationship between fiscal preemptions and contracting out varies contingent on the type of service provider. In sum, the findings suggest that local governments actively respond to institutional limitations on municipal fiscal activities in order to overcome supply and demand challenges, although the choice of service delivery method varies depending on fiscal conditions and the type of service provider.

Pleiotropic effects of statins in treatment of generalized periodontitis in patients with coronary artery disease: clinical and experimental study (literature review)

The high prevalence of generalized periodontitis in patients with coronary artery disease (CAD) requires improving the existing ways of periodontal treatment of this category of cardiac patients and finding new ones. Statins are a group of lipid-lowering medications that are widely used for primary and secondary prevention of cardiovascular diseases due to atherosclerotic vascular lesions. In addition to the cholesterol-lowering effect, statins have several pleiotropic effects, including anti-inflammatory, immune-stimulating, antibacterial, antioxidant, osteotropic etc. The analysis of scientific studies of native and foreign authors devoted to studying the influence of pleiotropic effects of statins on the condition of periodontal tissues revealed improvement of periodontal indicators, in particular, gum structure, reduction of the periodontal pockets depth, gum bleeding, and tooth mobility in patients on statin therapy. Experimental in vitro and in vivo studies show a decrease in proinflammatory cytokines (IL-6, IL-8, IL-1β, TNF-a, etc.), which play a key role in the development of generalized periodontitis, as well as the acceleration of reparative processes in alveolar bone tissue when administering topical statins. Despite the prospects of using statins as the main or additional agent in the treatment of periodontal diseases, the question of dosage and method of local delivery of the medication for avoiding the undesirable side effects remains controversial and requires further research.

Facilitation of Reparative Dentin Using a Drug Repositioning Approach With 4-Phenylbutric Acid

For hard tissue formation, cellular mechanisms, involved in protein folding, processing, and secretion play important roles in the endoplasmic reticulum (ER). In pathological and regeneration conditions, ER stress hinders proper formation and secretion of proteins, and tissue regeneration by unfolded protein synthesis. 4-Phenylbutyric acid (4PBA) is a chemical chaperone that alleviates ER stress through modulation in proteins folding and protein trafficking. However, previous studies about 4PBA only focused on the metabolic diseases rather than on hard tissue formation and regeneration. Herein, we evaluated the function of 4PBA in dentin regeneration using an exposed pulp animal model system via a local delivery method as a drug repositioning strategy. Our results showed altered morphological changes and cellular physiology with histology and immunohistochemistry. The 4PBA treatment modulated the inflammation reaction and resolved ER stress in the early stage of pulp exposure. In addition, 4PBA treatment activated blood vessel formation and TGF-β1 expression in the dentin-pulp complex. Micro-computed tomography and histological examinations confirmed the facilitated formation of the dentin bridge in the 4PBA-treated specimens. These results suggest that proper modulation of ER stress would be an important factor for secretion and patterned formation in dentin regeneration.

When and How Should I Use Antibiotic Cement in Primary and Revision Joint Arthroplasty?

Periprosthetic joint infections (PJIs) remain one of the most challenging and devastating complications associated with total joint arthroplasty. Therefore, prevention and the ability to effectively treat PJIs are critical. One such tool for both the prevention and treatment of PJIs is the use of antibiotic-loaded bone cement (ALBC). ALBC provides an effective local delivery method of antibiotics. Low dose (<2 g per 40-g batch) is commonly used for prophylaxis, while high dose (>3.6 g per 40-g batch) is used for the treatment of PJIs. This review focuses on the efficacy, safety, and cost-effectiveness of ALBC for both the prevention as well as the treatment of PJIs.

Injectable “nano-micron” combined gene-hydrogel microspheres for local treatment of osteoarthritis

Sustained and controllable local gene therapy is a potential method for treating osteoarthritis (OA) through the delivery of therapeutic microRNAs (miRNAs) to targeted cells. However, direct injection of crude miRNAs for local gene therapy is limited due to its inadequate transfection efficiency, easy inactivation, and short half-life. Here, a multifunctional gene vector, arginine, histidine, and phenylalanine-modified generation 5 polyamidoamine (named G5-AHP), was employed to form G5-AHP/miR-140 nanoparticles by forming a complex with microRNA-140 (miR-140). Then, the nanoparticles were entrapped in hydrogel microspheres (MSs) to construct a “nano-micron” combined gene hydrogel to alleviate the degradation of articular cartilage. Monodisperse gelatin methacryloyl hydrogel MSs were produced under ultraviolet light using one-step innovative microfluidic technology. Evenly dispersed MSs showed better injectability in sustainable and matrix metalloproteinases (MMPs)-responsive degradation methods for local gene delivery. The G5-AHP/miR-140 nanoparticles released from the MSs exhibited high gene transfection efficacy and long-term bioactivity, facilitated endocytosis, and thus maintained the metabolic balance of cartilage matrix by promoting the expression of type II collagen and inhibiting the expression of a disintegrin and metalloproteinase with thrombospondin motifs-5 and MMP13 in chondrocytes. After injection of the “nano-micron” combined gene hydrogel into the articular cavity of the OA model, the gene hydrogel increased G5-AHP/miR-140 nanoparticle retention, prevented articular cartilage degeneration, and reduced osteophyte formation in a surgically induced mouse model of OA. The present study provides a novel cell-free approach to alleviate the progression of OA that shows potential for locally injected gene delivery systems.

Prevention of chemotherapy-induced premature ovarian insufficiency in mice by scaffold-based local delivery of human embryonic stem cell-derived mesenchymal progenitor cells

BackgroundPremature ovarian insufficiency (POI) is one of the most serious side effects of chemotherapy in young cancer survivors. It may not only reduce fecundity but also affect lifelong health. There is no standard therapy for preserving ovarian health after chemotherapy. Recently, administration of embryonic stem cell-derived mesenchymal progenitor cells (ESC-MPCs) has been considered a new therapeutic option for preventing POI. However, the previous method of directly injecting cells into the veins of patients exhibits low efficacy and safety. This study aimed to develop safe and effective local delivery methods for the prevention of POI using two types of bioinspired scaffolds.MethodsFemale mice received intraperitoneal cisplatin for 10 days. On day 11, human ESC-MPCs were delivered through systemic administration using intravenous injection or local administration using intradermal injection and intradermal transplantation with a PLGA/MH sponge or hyaluronic acid (HA) gel (GEL) type of scaffold. PBS was injected intravenously as a negative control. Ovarian function and fertility were evaluated 4 weeks after transplantation. Follicle development was observed using hematoxylin and eosin staining. The plasma levels of sex hormones were measured using ELISA. Expression levels of anti-Müllerian hormone (AMH) and ki-67 were detected using immunostaining, and the quality of oocytes and embryos was evaluated after in vitro fertilization. The estrous cycles were observed at 2 months after transplantation.ResultsThe local administration of human ESC-MPCs using the bioinspired scaffold to the backs of mice effectively prolonged the cell survival rate in vivo. The HA GEL group exhibited the best recovered ovarian functions, including a significantly increased number of ovarian reserves, estrogen levels, and AMH levels and decreased apoptotic levels. Furthermore, the HA GEL group showed improved quality of oocytes and embryos and estrous cycle regularity.ConclusionsHA GEL scaffolds can be used as new delivery platforms for ESC-MPC therapy, and this method may provide a novel option for the clinical treatment of chemotherapy-induced POI.

Delivery Approaches for Therapeutic Genome Editing and Challenges.

Impressive therapeutic advances have been possible through the advent of zinc-finger nucleases and transcription activator-like effector nucleases. However, discovery of the more efficient and highly tailorable clustered regularly interspaced short palindromic repeats (CRISPR) and associated proteins (Cas9) has provided unprecedented gene-editing capabilities for treatment of various inherited and acquired diseases. Despite recent clinical trials, a major barrier for therapeutic gene editing is the absence of safe and effective methods for local and systemic delivery of gene-editing reagents. In this review, we elaborate on the challenges and provide practical considerations for improving gene editing. Specifically, we highlight issues associated with delivery of gene-editing tools into clinically relevant cells.

Analysis of Shortcomings Found in Most Appropriate Housing Delivery Method for Ameliorating Customer Satisfaction

Identify most appropriate housing delivery method is one of the critical emerging issues in the developing due to poor standard of living in cities. The scale and speed of urbanization and high population growth rate in India will pose an unprecedented managerial and policy level challenge on housing quality in residential areas. On the other side many stock of house were found vacant or non-usable. Even uses of an appropriate housing delivery method, some gaps /shortcoming are identifying. If these gaps can fulfill these gaps and can enhance customer satisfaction. This study was developing by using actual construction case data in quantitative data analysis methods such as Estimate track Estimate and Analytical Hierarchical process. This research focuses on the housing areas as understand primarily by available local housing delivery methods. This aim of the research is to develop a index for evaluating housing delivery performance of housing areas to improve the customer satisfaction of existing as well as upcoming housing areas.