Trypsin-encoding gene function of efficient star polycation nanomaterial-mediated dsRNA feeding delivery system of Grapholita molesta.

BACKGROUND: Grapholita molesta is an important and harmful fruit pest worldwide, with widespread feeding hosts. Trypsin, an indispensable hydrolytic digestive protease in the insect gut, is crucial in digestion, growth and development. We analyzed the characteristics of the trypsin-encoding genes, screened for the optimal dose of RNAi mediated by nanocarriers, and investigated various indices of larval growth and development of G. molesta. RESULTS: Gut content (GC) and RNase A degraded double-stranded RNA (dsRNA), with a faster degradation rate at higher concentrations. Star polycation (SPc) nanomaterials protected dsGFP from degradation by anion-cation binding and did not migrate through agarose gel. The key conserved motifs of the trypsin-encoding genes were similar, exhibiting high homology with those in other lepidopteran insects. An interference efficiency of ≈70% was achieved with SPc nanomaterial-mediated RNA interference with 0.05 µg dsRNA. The efficiency of continuous interference was stable. Trypsin activity, body weight of 8-day-old larvae, pupal weight and emergence rate were significantly reduced, and the larval stage was significantly prolonged. CONCLUSION: The investigated trypsin gene is a key target gene in the growth and development of G. molesta. We investigated the efficiency and convenience of feeding SPc nanomaterials in a functional study of insects. Our results provide valuable data for the development of efficient trypsin-targeting pesticides. © 2024 Society of Chemical Industry.

Advanced Nanomedicine Approaches for Myocardial Infarction Treatment.

Myocardial infarction, usually caused by the rupture of atherosclerotic plaque, leads to irreversible ischemic cardiomyocyte death within hours followed by impaired cardiac performance or even heart failure. Current interventional reperfusion strategies for myocardial infarction still face high mortality with the development of heart failure. Nanomaterial-based therapy has made great progress in reducing infarct size and promoting cardiac repair after MI, although most studies are preclinical trials. This review focuses primarily on recent progress (2016-now) in the development of various nanomedicines in the treatment of myocardial infarction. We summarize these applications with the strategy of mechanism including anti-cardiomyocyte death strategy, activation of neovascularization, antioxidants strategy, immunomodulation, anti-cardiac remodeling, and cardiac repair.

An intelligent Cu/ZIF-8-based nanodrug delivery system for tumor-specific and synergistic therapy via tumor microenvironment-responsive cascade reaction.

An intelligent nanodrug delivery system (Cu/ZIF-8@GOx-DOX@HA, hereafter CZGDH) consisting of Cu-doped zeolite imidazolate framework-8 (Cu/ZIF-8, hereafter CZ), glucose oxidase (GOx), doxorubicin (DOX), and hyaluronic acid (HA) was established for targeted drug delivery and synergistic therapy of tumors. The CZGDH specifically entered tumor cells through the targeting effect of HA and exhibited acidity-triggered biodegradation for subsequent release of GOx, DOX, and Cu2+ in the tumor microenvironment (TME). The GOx oxidized the glucose (Glu) in tumor cells to produce H2O2 and gluconic acid for starvation therapy (ST). The DOX entered the intratumoral cell nucleus for chemotherapy (CT). The released Cu2+ consumed the overexpressed glutathione (GSH) in tumor cells to produce Cu+. The generated Cu+ and H2O2 triggered the Fenton-like reaction to generate toxic hydroxyl radicals (·OH), which disrupted the redox balance of tumor cells and effectively killed tumor cells for chemodynamic therapy (CDT). Therefore, synergistic multimodal tumor treatment via TME-activated cascade reaction was achieved. The nanodrug delivery system has a high drug loading rate (48.3 wt%), and the three-mode synergistic therapy has a strong killing effect on tumor cells (67.45%).

Liposomal Nanomaterials: A Rising Star in Glioma Treatment.

Glioma is a primary malignant tumor in the central nervous system. In recent years, the treatment of glioma has developed rapidly, but the overall survival of glioma patients has not significantly improved. Due to the presence of the blood-brain barrier and intracranial tumor barrier, many drugs with good effects to cure glioma in vitro cannot be accurately transported to the corresponding lesions. In order to enable anti-tumor drugs to overcome the barriers and target glioma, nanodrug delivery systems have emerged recently. It is gratifying that liposomes, as a multifunctional nanodrug delivery carrier, which can be compatible with hydrophilic and hydrophobic drugs, easily functionalized by various targeted ligands, biodegradable, and hypoimmunogenic in vivo, has become a quality choice to solve the intractable problem of glioma medication. Therefore, we focused on the liposome nanodrug delivery system, and summarized its current research progress in glioma. Hopefully, this review may provide new ideas for the research and development of liposome-based nanomaterials for the clinical treatment of glioma.

pH-Responsive Mesoporous Silica Nanoparticles Loaded with Naringin for Targeted Osteoclast Inhibition and Bone Regeneration.

Background: It is well-established that osteoclast activity is significantly influenced by fluctuations in intracellular pH. Consequently, a pH-sensitive gated nano-drug delivery system represents a promising therapeutic approach to mitigate osteoclast overactivity. Our prior research indicated that naringin, a natural flavonoid, effectively mitigates osteoclast activity. However, naringin showed low oral availability and short half-life, which hinders its clinical application. We developed a drug delivery system wherein chitosan, as gatekeepers, coats mesoporous silica nanoparticles loaded with naringin (CS@MSNs-Naringin). However, the inhibitory effects of CS@MSNs-Naringin on osteoclasts and the underlying mechanisms remain unclear, warranting further research. Methods: First, we synthesized CS@MSNs-Naringin and conducted a comprehensive characterization. We also measured drug release rates in a pH gradient solution and verified its biosafety. Subsequently, we investigated the impact of CS@MSNs-Naringin on osteoclasts induced by bone marrow-derived macrophages, focusing on differentiation and bone resorption activity while exploring potential mechanisms. Finally, we established a rat model of bilateral critical-sized calvarial bone defects, in which CS@MSNs-Naringin was dispersed in GelMA hydrogel to achieve in situ drug delivery. We observed the ability of CS@MSNs-Naringin to promote bone regeneration and inhibit osteoclast activity in vivo. Results: CS@MSNs-Naringin exhibited high uniformity and dispersity, low cytotoxicity (concentration≤120 µg/mL), and significant pH sensitivity. In vitro, compared to Naringin and MSNs-Naringin, CS@MSNs-Naringin more effectively inhibited the formation and bone resorption activity of osteoclasts. This effect was accompanied by decreased phosphorylation of key factors in the NF-κB and MAPK signaling pathways, increased apoptosis levels, and a subsequent reduction in the production of osteoclast-specific genes and proteins. In vivo, CS@MSNs-Naringin outperformed Naringin and MSNs-Naringin, promoting new bone formation while inhibiting osteoclast activity to a greater extent. Conclusion: Our research suggested that CS@MSNs-Naringin exhibited the strikingly ability to anti-osteoclasts in vitro and in vivo, moreover promoted bone regeneration in the calvarial bone defect.

Delivery of minoxidil encapsulated in cyclodextrins with photoacoustic waves enhances hair growth.

The current pharmacological management of androgenetic alopecia is inconvenient and requires a discipline that patients find difficult to follow. This reduces compliance with treatment and satisfaction with results. It is important to propose treatment regimens that increase patient compliance and reduce adverse effects. This work describes transdermal delivery of minoxidil partially encapsulated in ß-cyclodextrin and assisted by photoacoustic waves. Photoacoustic waves transiently increase the permeability of the skin and allow for the delivery of encapsulated minoxidil. A minoxidil gel formulation was developed and the transdermal delivery was studied in vitro in the presence and absence of photoacoustic waves. A 5-min stimulus with photoacoustic waves generated by light-to-pressure transducers increases minoxidil transdermal delivery flux by approximately 3-fold. The flux of a 1% minoxidil formulation promoted by photoacoustic waves is similar to the passive flux of a 2% minoxidil commercial formulation. Release of minoxidil from ß-cyclodextrin increases dermal exposure without increasing peak systemic exposure. This promotes hair growth with fewer treatments and reduced adverse effects. In vivo studies using encapsulated minoxidil and photoacoustic waves yielded 86% hair coat recovery (vs. 29% in the control group) and no changes in the blood pressure.

[Advances in Nanotechnology-Based Drug Delivery Systems in the Treatment of Hepatocellular Carcinoma].

Primary liver cancer is one of the most common malignant tumors of the digestive system,of which hepatocellular carcinoma (HCC) accounts for more than 90% of the total cases.The patients with early HCC treated by surgical resection generally demonstrate good prognosis.However,due to the insidious onset,HCC in the vast majority of patients has progressed to the mid-to-late stage when being diagnosed.As a result,surgical treatment has unsatisfactory effects,and non-surgical treatment methods generally have severe side effects and low tumor selectivity.Nanoparticles (NP) with small sizes,large specific surface areas,and unique physical and chemical properties have become potential carriers for the delivery of therapeutic agents such as drugs,genes,and cytokines.The nano-delivery systems with NP as the carrier can regulate the metabolism and transformation of drugs,genes,and cytokines in vivo from time,space,and dose via functional modification,showing great potential in the treatment of HCC.This paper introduces the current status and advantages of several common nano-delivery systems,including organic nano-carriers,inorganic nano-carriers,and exosomes,in the treatment of HCC.Furthermore,this paper summarizes the mechanisms of NP-based nano-carriers in treating HCC and provides reference for the development of new nano-delivery systems.

TiO2 nanotubes with customized diameters for local drug delivery systems.

In this study, we evaluated the drug release behavior of diameter customized TiO2 nanotube layers fabricated by anodization with various applied voltage sequences: conventional constant applied potentials of 20 V (45 nm) and 60 V (80 nm), a 20/60 V stepped potential (50 nm [two-diameter]), and a 20-60 V swept potential (49 nm [full-tapered]) (values in parentheses indicate the inner tube diameter at the top part of nanotube layers). The structures of the 50 nm (two-diameter) and 49 nm (full-tapered) samples had smaller inner diameters at the top part of nanotube layers than that of the 80 nm sample, while the outer diameters at the bottom part of nanotube layers were almost the same size as the 80 nm sample. The 80 nm sample, which had the largest nanotube diameter and length, exhibited the greatest burst release, followed by the 50 nm (two-diameter), 49 nm (full-tapered), and 45 nm samples. The initial burst released drug amounts and release rates from the 50 nm (two-diameter) and 49 nm (full-tapered) samples were significantly suppressed by the smaller tube top. On the other hand, the largest proportion of the slow released drug amount to the total released drug amount was observed for the 50 nm (two-diameter) sample. Thus, 50 nm (two-diameter) achieved suppressed initial burst release and large storage capacity. Therefore, this study has, for the first time, applied TiO2 nanotube layers with modulated diameters (two-diameter and full-tapered) to the realization of a localized drug delivery system (LDDS) with customized drug release properties.

A rapid protocol for synthesis of chitosan nanoparticles with ideal physicochemical features.

In this research, an innovative protocol is introduced to address crucial deficiencies in the formulation of chitosan nanoparticles (Cs NPs). While NPs show potential in drug delivery systems (DDSs), their application in the clinic is hindered by various drawbacks, such as toxicity, high material costs, and time-consuming and challenging preparation procedures. Within polymer-based NPs, Cs is a plentiful natural substance derived from the deacetylation of chitin, which can be sourced from the shells of shrimp or crab. Cs NPs can be formulated using the ionic gelation technique, which involves the use of a negatively charged agent, such as tripolyphosphate (TPP), as a crosslinking agent. Even though Cs is a cost-effective and biocompatible material, the formulation of Cs NPs with the correct size and surface electrical charge (zeta potential) presents a persistent challenge. In this study, various techniques were employed to analyze the prepared Cs NPs. The size and surface charge of the NPs were evaluated using dynamic light scattering (DLS). Morphological analysis was conducted using field emission-scanning electron microscopy (FE-SEM). The chemical composition and formation of Cs NPs were investigated using Fourier transform infrared (FTIR). The stability analysis was confirmed through X-ray diffraction (XRD) analysis. Lastly, the biocompatibility of the NPs was assessed through cell cytotoxicity evaluation using the MTT assay. Moreover, here, 11 formulations with different parameters such as reaction pH, Cs:TPP ratio, type of Cs/TPP, and ultrasonication procedure were prepared. Formulation 11 was chosen as the optimized formulation based on its high stability of more than three months, biocompatibility, nanosize of 75.6 ± 18.24 nm, and zeta potential of +26.7 mV. To conclude, the method described here is easy and reproducible and can be used for facile preparation of Cs NPs with desirable physicochemical characteristics and engineering ideal platforms for drug delivery purposes.

Comparison of two self-nanoemulsifying drug delivery systems using different solidification techniques for enhanced solubility and oral bioavailability of poorly water-soluble celecoxib.

In this study, we aimed to develop a solid self-nanoemulsifying drug delivery system (S-SNEDDS) and a solid self-nanoemulsifying granule system (S-SNEGS) to enhance the solubility and oral bioavailability of celecoxib. This process involved the preparation of a liquid SNEDDS (L-SNEDDS) and its subsequent solidification into a S-SNEDDS and a S-SNEGS. The L-SNEDDS consisted of celecoxib (drug), Captex® 355 (Captex; oil), Tween® 80 (Tween 80; surfactant) and D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS; cosurfactant) in a weight ratio of 3.5:25:60:15 to produce the smallest nanoemulsion droplet size. The S-SNEDDS and S-SNEGS were prepared with L-SNEDDS/Ca-silicate/Avicel PH 101 in a weight ratio of 103.5:50:0 using a spray dryer and 103.5:50:100 using a fluid bed granulator, respectively. We compared the two novel developed systems and celecoxib powder based on their solubility, dissolution rate, physicochemical properties, flow properties and oral bioavailability in rats. S-SNEGS showed a significant improvement in solubility and dissolution rate compared to S-SNEDDS and celecoxib powder. Both systems had been converted from crystalline drug to amorphous form. Furthermore, S-SNEGS exhibited a significantly reduced angle of repose, compressibility index and Hausner ratio than S-SNEDDS, suggesting that S-SNEGS was significantly superior in flow properties. Compared to S-SNEDDS and celecoxib powder, S-SNEGS increased the oral bioavailability (AUC value) in rats by 1.3 and 4.5-fold, respectively. Therefore, S-SNEGS wolud be recommended as a solid self-nanoemulsifying system suitable for poorly water-soluble celecoxib.

Cartilage decellularized matrix hydrogel loaded with protocatechualdehyde for targeted epiphycan treatment of osteoarthritis.

Osteoarthritis (OA) is a prevalent chronic disease, characterized by chronic inflammation and cartilage degradation. This study aims to deepen the understanding of OA's pathophysiology and to develop novel therapeutic strategies. Our study underscores the pivotal role of Epiphycan (EPYC) and the IL-17 signaling pathway in OA. EPYC, an essential extracellular matrix constituent, has been found to exhibit a positive correlation with the severity of OA. We have discovered that EPYC modulates the activation of the IL-17 signaling pathway within chondrocytes by regulating the interaction between IL-17A and its receptor, IL-17RA. This regulatory mechanism underscores the intricate interplay between the extracellular matrix and immune signaling in the pathogenesis of OA Another finding of our study is the therapeutic effectiveness of protocatechualdehyde (PAH) in OA. PAH significantly reduces chondrocyte hypertrophy and supports cartilage tissue recovery.by targets EPYC. To reduce the side effects of orally administered PAH and maintain its effective drug concentration, we have developed a decellularized matrix hydrogel loaded with PAH for intra-articular injection. This novel drug delivery system is advantageous in minimizing drug-related side effects and ensuring sustained release PAH within the joint cavity.

Designing Dual-Responsive Drug Delivery Systems: The Role of Phase Change Materials and Metal-Organic Frameworks.

Stimuli-responsive drug delivery systems (DDSs) offer precise control over drug release, enhancing therapeutic efficacy and minimizing side effects. This review focuses on DDSs that leverage the unique capabilities of phase change materials (PCMs) and metal-organic frameworks (MOFs) to achieve controlled drug release in response to pH and temperature changes. Specifically, this review highlights the use of a combination of lauric and stearic acids as PCMs that melt slightly above body temperature, providing a thermally responsive mechanism for drug release. Additionally, this review delves into the properties of zeolitic imidazolate framework-8 (ZIF-8), a stable MOF under physiological conditions that decomposes in acidic environments, thus offering pH-sensitive drug release capabilities. The integration of these materials enables the fabrication of complex structures that encapsulate drugs within ZIF-8 or are enveloped by PCM layers, ensuring that drug release is tightly controlled by either temperature or pH levels, or both. This review provides comprehensive insights into the core design principles, material selections, and potential biomedical applications of dual-stimuli responsive DDSs, highlighting the future directions and challenges in this innovative field.

Dual-Drug Nanomedicine Assembly with Synergistic Anti-Aneurysmal Effects via Inflammation Suppression and Extracellular Matrix Stabilization.

Abdominal aortic aneurysm (AAA) represents a critical cardiovascular condition characterized by localized dilation of the abdominal aorta, carrying a significant risk of rupture and mortality. Current treatment options are limited, necessitating novel therapeutic approaches. This study investigates the potential of a pioneering nanodrug delivery system, RAP@PFB, in mitigating AAA progression. RAP@PFB integrates pentagalloyl glucose (PGG) and rapamycin (RAP) within a metal-organic-framework (MOF) structure through a facile assembly process, ensuring remarkable drug loading capacity and colloidal stability. The synergistic effects of PGG, a polyphenolic antioxidant, and RAP, an mTOR inhibitor, collectively regulate key players in AAA pathogenesis, such as macrophages and smooth muscle cells (SMCs). In macrophages, RAP@PFB efficiently scavenges various free radicals, suppresses inflammation, and promotes M1-to-M2 phenotype repolarization. In SMCs, it inhibits apoptosis and calcification, thereby stabilizing the extracellular matrix and reducing the risk of AAA rupture. Administered intravenously, RAP@PFB exhibits effective accumulation at the AAA site, demonstrating robust efficacy in reducing AAA progression through multiple mechanisms. Moreover, RAP@PFB demonstrates favorable biosafety profiles, supporting its potential translation into clinical applications for AAA therapy.

Long acting delivery and therapies for neovascular age-related macular degeneration.

INTRODUCTION: Neovascular age-related macular degeneration (nAMD) represents a leading cause of severe visual impairment in individuals over 50 years of age in developed nations. Intravitreal anti-vascular endothelial growth factor (VEGF) injections have become the standard of care for treating nAMD; however, monthly or bimonthly dosing represents significant time and cost burden due to the disease's chronic nature and limited medication half-life. AREAS COVERED: This review summarizes innovative therapeutics and delivery methods for nAMD. Emerging methods for extended drug delivery include high molar concentration anti-VEGF drugs, intravitreal sustained release devices, reservoirs for intravitreal delivery, and gene therapy biofactories. In addition to VEGF-A, therapies targeting inhibition of VEGF-C and D, the angiopoetin-2 (Ang-2)/Tie-2 pathway, tyrosine kinases, and integrins are reviewed. EXPERT OPINION: The evolving therapeutic landscape of nAMD is rapidly expanding our toolkit for effective and durable treatment. Recent FDA approvals of faricimab (Vabysmo) and high dose aflibercept (Eylea HD) for nAMD with potential extension of injection intervals up to four months have been promising developments for patients and providers alike. Further research and innovation, including novel delivery techniques and pharmacologic targets, is necessary to validate the efficacy of developing therapeutics and characterize real-world outcomes. demonstrating promise in expanding treatment durability.

Advances in ophthalmic therapeutic delivery: A comprehensive overview of present and future directions.

Ophthalmic treatment demands precision and consistency in delivering therapeutic agents over extended periods to address many conditions, from common eye disorders to complex diseases. This diversity necessitates a range of delivery strategies, each tailored to specific needs. We delve into various delivery cargos that are pivotal in ophthalmic care. These cargos encompass biodegradable implants that gradually release medication, nonbiodegradable implants for sustained drug delivery, refillable tools allowing flexibility in treatment, hydrogels capable of retaining substances while maintaining ocular comfort, and advanced nanotechnology devices that precisely target eye tissues. Within each cargo category, we explore cutting-edge research-level approaches and FDA-approved methods, providing a thorough overview of the current state of ophthalmic drug delivery. In particular, our focus on nanotechnology reveals the promising potential for gene delivery, cell therapy administration, and the implantation of active devices directly into the retina. These advancements hold the key to more effective, personalized, and minimally- invasive ophthalmic treatments, revolutionizing the field of eye care.

A phase 4 randomized active-controlled clinical study to compare the efficacy and safety of sustained-release pregabalin with immediate-release pregabalin in type 2 diabetic patients with peripheral neuropathic pain.

AIMS: The objective of this study was to demonstrate that sustained-release (SR) pregabalin is non-inferior to immediate-release (IR) pregabalin in attenuating diabetic peripheral neuropathic (DPN) pain along with patient satisfaction and compliance. METHODS: This was an 8-week, randomized, active-controlled, open-label, phase 4 study. Eligible subjects who had been on IR pregabalin for 4 weeks were randomized to 1:1 ratio to either continue with twice-daily IR pregabalin (75 mg), or to switch to once-daily SR pregabalin (150 mg). Primary efficacy endpoint was the change in visual analogue scale (VAS) scores after 8 weeks of treatment compared to baseline in both SR and IR pregabalin groups. RESULTS: Among 130 randomized subjects, 125 patients were included in full analysis set. For the change in VAS pain score, the least squares (LS) mean were -17.95 (SR pregabalin) and -18.74 (IR pregabalin) and the LS mean difference between both groups was 0.79, with the upper limit of the 95 % confidence interval [-5.99, 7.58] below the pre-specified non-inferiority margin of 9.2 mm. CONCLUSIONS: This study demonstrates that the new once-daily SR pregabalin formulation is not different to the twice-daily IR pregabalin in alleviating DPN pain, indicating its potential as a promising treatment for DPN pain with a comparable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05624853.

Applications of polysaccharides in enzyme-triggered oral colon-specific drug delivery systems: A review.

Enzyme-triggered oral colon-specific drug delivery system (EtOCDDS1) can withstand the harsh stomach and small intestine environments, releasing encapsulated drugs selectively in the colon in response to colonic microflora, exerting local or systematic therapeutic effects. EtOCDDS boasts high colon targetability, enhanced drug bioavailability, and reduced systemic side effects. Polysaccharides are extensively used in enzyme-triggered oral colon-specific drug delivery systems, and its colon targetability has been widely confirmed, as their properties meet the demand of EtOCDDS. Polysaccharides, known for their high safety and excellent biocompatibility, feature modifiable structures. Some remain undigested in the stomach and small intestine, whether in their natural state or after modifications, and are exclusively broken down by colon-resident microbiota. Such characteristics make them ideal materials for EtOCDDS. This article reviews the design principles of EtOCDDS as well as commonly used polysaccharides and their characteristics, modifications, applications and specific mechanism for colon targeting. The article concludes by summarizing the limitations and potential of ETOCDDS to stimulate the development of innovative design approaches.

Travoprost Intracameral Implant Demonstrates Superior IOP Lowering Versus Topical Prostaglandin Analog Monotherapy in Patients with Open-Angle Glaucoma or Ocular Hypertension.

INTRODUCTION: This study was conducted to analyze and compare the intraocular pressure (IOP) treatment effect of the slow-eluting (SE) travoprost intracameral implant to the IOP treatment effect of topical prostaglandin analog (PGA) monotherapy in a subgroup of subjects who were on pre-study PGA monotherapy prior to enrollment in the two pivotal phase 3 trials of the travoprost intracameral implant. METHODS: A combined study population of 133 subjects from two phase 3 trials, who were on topical PGA monotherapy at screening, subsequently underwent a washout period from their topical PGA, and then were randomized and administered an SE travoprost intracameral implant. The subjects were analyzed for the IOP treatment effects of the pre-study topical PGA monotherapy and the in-study SE travoprost intracameral implant. Paired t-tests were used to compare the difference in screening minus post-washout baseline IOP versus month 3 minus post-washout baseline IOP. The IOP-lowering efficacy in eyes administered an SE travoprost intracameral implant was compared to the IOP lowering in the same eyes while on a topical PGA monotherapy prior to study entry. RESULTS: Pre-study topical PGA monotherapy and the SE travoprost intracameral implant demonstrated IOP treatment effects of -5.76 mmHg and -7.07 mmHg, respectively. The IOP-lowering treatment effect was significantly greater by 1.31 mmHg for the SE travoprost intracameral implant relative to pre-study PGA monotherapy (95% confidence interval: -2.01, -0.60; P = 0.0003). CONCLUSIONS: The SE travoprost intracameral implant demonstrated superior IOP-lowering treatment effect versus pre-study topical PGA monotherapy with a superiority margin that was both statistically significant and clinically meaningful. The greater IOP reduction from baseline while on the SE implant versus pre-study topical PGA monotherapy may be a reflection of the optimized adherence and continuous elution of PGA therapy into the anterior chamber achieved with the SE travoprost intracameral implant. TRIAL REGISTRATION: ClinicalTrials.gov identifiers, NCT03519386 and NCT03868124.

Preparation and characterization of the injectable pH- and temperature-sensitive pentablock hydrogel containing human growth hormone-loaded chitosan nanoparticles via electrospraying.

This research investigated the in vivo gelation, biodegradation, and drug release efficiency of a novel injectable sensitive drug delivery system for human growth hormone (HGh). This composite system comprises pH- and temperature-sensitive hydrogel, designated as oligomer serine-b-poly(lactide)-b-poly(ethylene glycol)-b-poly(lactide)-b-oligomer serine (OS-PLA-PEG-PLA-OS) pentablock copolymer, as matrix and electrosprayed HGh-loaded chitosan (HGh@CS) nanoparticles (NPs) as principal material. The proton nuclear magnetic resonance spectrum of the pH- and temperature-sensitive OS-PLA-PEG-PLA-OS pentablock copolymer hydrogel proved that this copolymer was successfully synthesized. The HGh was encapsulated in chitosan (CS) NPs by an electrospraying system in acetic acid with appropriate granulation parameters. The scanning electron microscopy images and size distribution showed that the HGh@CS NPs formed had an average diameter of 366.1 ± 214.5 nm with a discrete spherical shape and dispersed morphology. The sol-gel transition of complex gel based on HGh@CS NPs and OS-PLA-PEG-PLA-OS pentablock hydrogel was investigated at 15 °C and pH 7.8 in the sol state and gelled at 37 °C and pH 7.4, which is suitable for the physiological conditions of the human body. The HGh release experiment of the composite system was performed in an in vivo environment, which demonstrated the ability to release HGh, and underwent biodegradation within 32 days. The findings of the investigation revealed that the distribution of HGh@CS NPs into the hydrogel matrix not only improved the mechanical properties of the gel matrix but also controlled the drug release kinetics into the systematic bloodstream, which ultimately promotes the desired therapeutic body growth depending on the distinct concentration used.

A carrier free delivery system of a MAGL inhibitor is effective on ovarian cancer.

Monoacylglycerol lipase (MAGL) is a promising target for cancer therapy due to its involvement in lipid metabolism and its impact on cancer hallmarks like cell proliferation, migration, and tumor progression. A potent reversible MAGL inhibitor, MAGL23, has been recently developed by our group, demonstrating promising anticancer activities. To enhance its pharmacological properties, a nanoformulation using nanocrystals coated with albumin was prepared (MAGL23AF). In a previous work, the formulated inhibitor showed to maintain its potency in ovarian and colon cancer cell lines in terms of IC50, and the formulation was tested on mice in order to assess its biocompatibility, organs biodistribution and toxicity. In the present work, we expanded the investigation to assess the potential in vivo application of MAGL23AF. Stability assays in serum and in human derived microsomes showed a good structural stability in physiological conditions of MAGL23AF. Antitumor efficacy tested on mice bearing ovarian cancer tumor highlighted that MAGL23AF has a more potent antitumor efficacy compared to non-formulated drug and leads to a necrosis-driven cancer cell death. In vivo studies revealed that albumin-complexed nanocrystals improved the therapeutic window of MAGL23, exhibiting a favorable biodistribution with slightly increased accumulation in the tumor. In conclusion, the MAGL23AF showed increased in vitro stability in conditions mirroring the bloodstream environment and hepatic metabolism coupled with an optimal antitumor efficacy in vivo. These results not only validates the efficacy of our formulation but also positions it as a promising strategy for addressing challenges related to the solubility of drugs in body fluids.