RESUMEN

Glaucoma presents a significant global health concern and affects millions of individuals worldwide and predicted a high increase in prevalence of about 111 million by 2040. The current standard treatment involves hypotensive eye drops; however, challenges such as patient adherence and limited drug bioavailability hinder the treatment effectiveness. Nanopharmaceuticals or nanomedicines offer promising solutions to overcome these obstacles. In this manuscript, we summarized the current limitations of conventional antiglaucoma treatment, role of nanomedicine in glaucoma treatment, rational design, factors effecting the performance of nanomedicine and different types of nanocarriers in designing of nanomedicine along with their applications in glaucoma treatment from recent literature. Current clinical challenges that hinder real-time application of antiglaucoma nanomedicine are highlighted. Lastly, future directions are identified for improving the therapeutic potential and translation of antiglaucoma nanomedicine into clinic.

RESUMEN

Colorectal cancer (CRC) is a common and life-threatening neoplastic disease that continues to pose a formidable challenge to global health. The present work was performed to evaluate  the anticancer properties of betanin and betanin (BT) loaded starch nanoparticles (S-BT). The BT and S-BT were characterized by DLS, SEM, UV spectroscopy, XPS and FTIR. The cytotoxic effect was assessed by MTT and LDH assay. The apoptotic potential of BT and S-BT was assessed by DCFDA, Rh123, AO/EB and DAPI staining methods. Cell cycle arrest was depicted using flow cytometry. The antimetastatic potential of BT and S-BT was evaluated by wound healing assay. The S-BT showed a spherical morphology with a size of 175 nm. The betanin contained SNPs were found to have strong encapsulation efficiency and favorable release profiles. Both BT and S-BT exhibited cytotoxicity in SW480 cells but S-BT displayed increased cytotoxicity when compared to BT alone. Loss of mitochondrial membrane potential, nuclear fragmentation, chromatin condensation and generation of ROS, all indicative of apoptotic mode of cell death, were revealed by fluorescence imaging. The cells were arrested in the G2M phase. Moreover, both BT and S-BT were able to inhibit the migratory potential of SW480 cells. Overall, our results indicated that both BT and S-BT were able to induce anticancer effects; and, S-BT was found to have increased therapeutic efficacy when compared to BT alone.

RESUMEN

Core-shell nanostructures are powerful platforms for the development of novel nanoscale drug delivery systems with sustained drug release profiles. Coaxial electrospinning is facile and convenient for creating medicated core-shell nanostructures with elaborate designs with which the sustained-release behaviors of drug molecules can be intentionally adjusted. With resveratrol (RES) as a model for a poorly water-soluble drug and cellulose acetate (CA) and PVP as polymeric carriers, a brand-new electrospun core-shell nanostructure was fabricated in this study. The guest RES and the host CA molecules were designed to have a reverse gradient distribution within the core-shell nanostructures. Scanning electron microscope and transmission electron microscope evaluations verified that these nanofibers had linear morphologies, without beads or spindles, and an obvious core-shell double-chamber structure. The X-ray diffraction patterns and Fourier transform infrared spectroscopic results indicated that the involved components were highly compatible and presented in an amorphous molecular distribution state. In vitro dissolution tests verified that the new core-shell structures were able to prevent the initial burst release, extend the continuous-release time period, and reduce the negative tailing-off release effect, thus ensuring a better sustained-release profile than the traditional blended drug-loaded nanofibers. The mechanism underlying the influence of the new core-shell structure with an RES/CA reverse gradient distribution on the behaviors of RES release is proposed. Based on this proof-of-concept demonstration, a series of advanced functional nanomaterials can be similarly developed based on the gradient distributions of functional molecules within electrospun multi-chamber nanostructures.

Asunto(s)

Celulosa , Preparaciones de Acción Retardada , Portadores de Fármacos , Liberación de Fármacos , Nanofibras , Resveratrol , Nanofibras/química , Preparaciones de Acción Retardada/química , Resveratrol/química , Resveratrol/administración & dosificación , Celulosa/química , Celulosa/análogos & derivados , Portadores de Fármacos/química , Polímeros/química , Espectroscopía Infrarroja por Transformada de Fourier , Sistemas de Liberación de Medicamentos/métodos , Difracción de Rayos X

RESUMEN

Transdermal drug delivery (TDD) is an attractive route of administration, providing several advantages, especially over oral and parenteral routes. However, TDD is significantly restricted due to the barrier imposed by the uppermost layer of the skin, the stratum corneum (SC). Microneedles is a physical enhancement technique that efficiently pierces the SC and facilitates the delivery of both lipophilic and hydrophilic molecules. Dissolving microneedles is a commonly used type that is fabricated utilizing various biodegradable and biocompatible polymers, such as polylactic acid, polyglycolic acid, or poly(lactide-co-glycolide) (PLGA). Such polymers also promote the prolonged release of the drug due to the slow degradation of the polymer matrix following its insertion. We selected carfilzomib, a small therapeutic peptide (MW: 719.924 g/mol, log P 4.19), as a model drug to fabricate a microneedle-based sustained delivery system. This study is a proof-of-concept investigation in which we fabricated PLGA microneedles using four types of PLGA (50-2A, 50-5A, 75-5A, and 50-7P) to evaluate the feasibility of long-acting transdermal delivery of carfilzomib. Micromolding technique was used to fabricate the PLGA microneedles and characterization tests, including Fourier transform infrared spectroscopy, insertion capability using the skin simulant Parafilm model, histological evaluation, scanning electron microscopy, and confocal microscopy were conducted. In vitro release and permeation testing were conducted in vertical Franz diffusion cells. N-methyl pyrrolidone was utilized as the organic solvent and microneedles were solidified in controlled conditions, which led to good mechanical strength. Both in vitro release and permeation testing showed sustained profiles of carfilzomib over 7 days. The release and permeation were significantly influenced by the molecular weight of PLGA and the lipophilic properties of carfilzomib.

RESUMEN

Schizophrenia is a severe mental disorder that affects millions of people worldwide. Several atypical antipsychotic medications, including paliperidone (PPD), has been developed and proven effective in treating it. To date, four PPD extended-release products have been launched commercially, providing up to six months of therapeutic effect with a single administration. However, the need for hospital injections by professional healthcare workers not only lead to poor patients' adherence, but also put additional pressure on the healthcare system. Therefore, three PPD microarray patch (PPD MAP) systems based on dissolving microneedle technology and implantable microneedle technology were developed in this work. The two dissolving microarray patch systems contained either PPD crude drug (PPD DMAP-CD) or PPD nanocrystal (PPD DMAP-NC) and the implantable MAP contained PPD crude drug (PPD IMAP). All three types of PPD MAPs showed excellent mechanical and insertion properties as they achieved over 256 µm insertion depth in skin model. In vitro release study showed that PPD released from IMAP in a much more sustained manner (up to 14 days) than PPD did from DMAPs (7 days), with only 20 % initial burst release from IMAP compared with 43-71 % from DMAPs. The MAP dissolution study showed that both DMAPs can be immediately dissolved within less than 3 min once inserted into the skin, indicating a faster action potential compared with IMAP. Ex vivo delivery study showed that 1.68 ±â€¯0.23 mg, 1.39 ±â€¯0.07 mg, and 1.18 ±â€¯0.12 mg were delivered from DMAP-CD, DMAP-NC and IMAP, respectively, demonstrating that over 50 % and up to 70 % of PPD in the MAPs can be delivered into the skin. The IMAP offers most sustained release of PPD whereas DMAP-NC exhibits fastest PPD release (11.19 % vs 20.01 % into Franz cell receiver compartment over 24 h). This work presents a promising alternative for the sustained delivery of antipsychotic drugs, allowing for patient self-administration and extended release concurrently. Patients may potentially use both DMAP and IMAP to achieve a sustained release of PPD while also avoid having an initial therapeutic lag.

RESUMEN

Continuous use of oral NSAIDs can damage mucosal membrane, which results in decreased bioavailability and non-compliance with the therapy. But the use of sustained release drug delivery systems might offer a solution. Objective was to synthesize mucoadhesive SR microspheres by using different combinations of pectin (PEC) and its thiolated derivative (T-PEC3100) for improved loxoprofen (LS) permeation. Thiolated pectin (T-PEC) was synthesized by the esterification method using thioglycolic acid. Thiolation was confirmed by thiol group quantification and charring point determination. Further characterization was done by Fourier Transform Infrared spectroscopy (FTIR), and Scanning electron microscopy (SEM). Ex-vivo mucoadhesion study was performed to confirm the improved characteristics. Microspheres (MS) were prepared using different ratios of PEC/T-PEC by solvent evaporation method and their particle size and surface morphology were evaluated. Mucus permeation study was carried out using the trans-well plate method. Sustained release behavior of prepared microspheres was investigated through the edema inhibition method in albino rats. T-PEC3100 was considered the optimum formulation for further evaluation and contained maximum thiol group content. FTIR spectra showed a characteristic peak of -SH and charring point was also changed considerably confirming the successful thiolation of PEC. SEM results showed spherical microspheres in the size range of 2-10 µm. Thiol-rich formulation of MS exhibited more than 80 % release after 12 h and maximum absorbable dose (MAD) was calculated as 400 µg % inhibition of edema in MS treated group was slowly attained initially but the reduction in inflammation was detected even after 24 h as compared to control group. Promising results from In-vivo edema inhibition study suggest the possible use of these thiolated MS in formulating sustained release formulation for arthritis.

RESUMEN

Reducing pesticide residues while extending their efficacy period is a critical challenge in the development of controlled-release pesticides. This study focuses on loading avermectin onto lignin-modified epoxy resin nanocarriers via the creation of photostable nanocapsules (NCs) for evaluating their efficacy against Plutella xylostella. This study also assesses the NCs' resistance to water scour on plant leaves by comparing them with traditional preparations. These NCs feature a stable core-shell structure, an encapsulation efficiency of 92.90 % and slow-release properties. Compared to emulsifiable concentrate (EC) and microemulsion (ME) under UV irradiation, the loading of nanocarriers significantly prolonged the degradation time of avermectin by fivefold. The Nano-formula demonstrated enhanced insecticidal activity in comparison to traditional preparations. Field tests revealed that the efficacy of the NCs on Day 7 (92.55 %) and Day 14 (78.54 %) significantly surpassed that of traditional preparations. Additionally, NCs are more readily washed off cabbage leaves by water than EC and ME, aiding in the reduction of pesticide residues. This technology is particularly suitable for leafy vegetable crops in arid regions or greenhouses, enhancing effectiveness period while minimizing pesticide residues. This research offers novel insights and directions for the development of controlled-release pesticides.

RESUMEN

Treating diabetic retinopathy (DR) effectively is challenging, aiming for high efficacy with minimal discomfort. While intravitreal injection is the current standard, it has several disadvantages. Implantable systems offer an alternative, less invasive, with long-lasting effects drug delivery system (DDS). The current study aims to develop a soft, minimally invasive, biodegradable, and bioadhesive material-based hydrogel scaffold to prevent common issues with implants. A grid-shaped scaffold was created using coaxial 3D printing (3DP) to extrude two bioinks in a single filament. The scaffold comprises an inner core of curcumin-loaded liposomes (CUR-LPs) that prepared by microfluidics (MFs) embedded in a hydrogel of hydroxyethyl cellulose (HEC), and an outer layer of hyaluronic acid-chitosan matrix with free resveratrol (RSV), delivering two Sirt1 agonists synergistically activating Sirt1 downregulated in DR. Optimized liposomes, prepared via MFs, exhibit suitable properties for retinal delivery in terms of size (<200 nm), polydispersity index (PDI) (<0.3), neutral zeta potential (ZP), encapsulation efficiency (∼97 %), and stability up to 4 weeks. Mechanical studies confirm scaffold elasticity for easy implantation. The release profiles show sustained release of both molecules, with different patterns related to different localization of the molecules. RSV released initially after 30 min with a total release more than 90 % at 336 h. CUR release starts after 24 h with only 4.78 % of CUR released before and gradually released thanks to its internal localization in the scaffold. Liposomes and hydrogels can generate dual drug-loaded 3D structures with sustained release. Microscopic analysis confirms optimal distribution of liposomes within the hydrogel scaffold. The latter resulted compatible in vitro with human retinal microvascular endothelial cells up to 72 h of exposition. The hydrogel scaffold, composed of hyaluronic acid and chitosan, shows promise for prolonged treatment and minimally invasive surgery.

RESUMEN

The aim of present work was to develop and evaluate Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer. Ampelopsis Radix ethanolic extract was prepared by Soxhlet extraction process followed by development of phytosomes using lipids and other excipients. The phytosomes were evaluated for surface morphology, particle size analysis, zeta potential, encapsulation efficiency, drug loading, in vitro drug release, Cytotoxicity assay, cellular uptake studies were performed on HCT-116 and SW480 cell lines. In vivo antitumor activity was performed. The phytosomes were found spherical shape with smooth surface characteristics. The drug loading was observed between 29.27 to 42.10 % while particle size of 85 to 130 nm was found. Phytosomes showed desired release pattern which is required for cancer treatment. Phytosomes showed maximum antiproliferative activity on cell lines over the period of 24 hours and showed highest internalization within both types of cell lines. The survival rate of animals in phytosomes treated group was found to be 100% proving the safety and efficacy. Phytosomes showed highest antitumor activity as compared to other formulations. Study confirms the potential use Ampelopsis Radix ethanolic extract loaded phytosomes for improved efficacy in colorectal cancer.

Asunto(s)

Ampelopsis , Neoplasias Colorrectales , Etanol , Extractos Vegetales , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Humanos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Etanol/química , Animales , Ampelopsis/química , Células HCT116 , Tamaño de la Partícula , Liberación de Fármacos , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Ratones , Proliferación Celular/efectos de los fármacos , Fitoterapia , Fitosomas

RESUMEN

Oxidative stress has long been known as a pathogenic factor of ulcerative colitis. Superoxide dismutase (SOD) has been demonstrated to mitigate gut mucosal injury via combating oxidative stress. Herein, we developed SOD-loaded multivesicular liposomes (S-MVLs) as sustained-release depot for ulcerative colitis treatment. S-MVLs were spherical honeycomb-like particles with average particle size of 27.3 ± 5.4 µm and encapsulating efficiency of 78.7 ± 2.6 %. Moreover, the two-phase release profiles of SOD from S-MVLs were exhibited, that was, the burst release phase within 4 h and the sustained-release phase within 96 h. After intraperitoneally injecting S-MVLs, in situ retention time of SOD at bowel cavity extended by 4-fold in comparison with SOD solution. In vitro cells experiment showed that S-MVLs had the protective effect on LPS-treated RAW 264.7 cells via scavenging ROS and inhibiting pro-inflammatory cytokines production. S-MVLs ameliorated the body weight loss, DAI score and the colon shortening of colitis mice. Meanwhile, the colonic morphology and the epithelial barrier of colitis mice were effectively recovered after S-MVLs treatment. The therapeutic mechanism might be associated with polymerizing M1 macrophages to M2 phenotypes and alleviating oxidative stress. Collectively, multivesicular liposomes might be a promising sustained-release depot of SOD for ulcerative colitis treatments.

Asunto(s)

Preparaciones de Acción Retardada , Mucosa Intestinal , Liposomas , Estrés Oxidativo , Superóxido Dismutasa , Animales , Estrés Oxidativo/efectos de los fármacos , Liposomas/química , Ratones , Superóxido Dismutasa/metabolismo , Células RAW 264.7 , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Mucosa Intestinal/metabolismo , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Tamaño de la Partícula , Masculino , Colon/patología , Colon/efectos de los fármacos , Colon/metabolismo , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Colitis/patología , Ratones Endogámicos C57BL , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colitis Ulcerosa/inducido químicamente , Liberación de Fármacos , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

Fibres in the micro- and nanometre scale are suited to a broad range of applications, including drug delivery and tissue engineering. Electrospinning is the manufacturing method of choice, but it has some limitations. Novel pressure-driven fibre-forming techniques, like pressurised gyration (PG), overcome these limitations; however, the compatibility of PG with biological materials has not yet been evaluated in detail. For the first time, this limitation of PG was investigated by optimising PG for microbial cell processing and incorporating bacterial cultures into fibrous polymeric scaffolds for sustained release. Multiple polymer-solvent systems were trialled, including polyvinylpyrrolidone (PVP)/phosphate-buffered saline (PBS) 25% w/v, polyethylene oxide (PEO)/PBS 20% w/v, and PVP/ethanol 20% w/v. Rheological studies revealed the surface tension of the PVP/PBS, PEO/PBS, and PVP/ethanol polymer-solvent systems to be 73.2, 73.9, and 22.6 mN/m, respectively. Scanning electron microscopy showed the median fibre diameters to be between 9.8 µm and 26.1 µm, with PVP producing larger fibres. Overnight Bacillus subtilis cultures were then incorporated into the chosen polymeric solutions and processed into fibres using PG. The produced cell-loaded fibres were incubated in LB broth to assess the cell viability of the encapsulated cells. Colony counts post-incubation showed the PVP/PBS 25% fibres resulted in 60% bacterial growth, and PEO/PBS 20% fibres led to 47% bacterial growth, whereas PVP/ethanol 20% fibres did not lead to any bacterial growth. Based on the results gathered during this study, it can be concluded that PG offers a promising way of encapsulating cells and other sensitive biological products while having many notable advantages compared to electrospinning. This research demonstrates proof of concept research-based evidence and showcases the potential of pressurised gyration as a key disruptive innovation in probiotic delivery system design and manufacturing.

RESUMEN

BACKGROUND: Repeat-breeder cows repeatedly fail to conceive after at least three attempts and return to oestrus at apparently normal intervals. Repeat-breeder cows cause economic losses in dairy farms in different ways. OBJECTIVE: In the present study, we investigated the effect of sustained-release progesterone injection in two different doses on the expression of interferon-related genes in repeat-breeder dairy cows. METHODS: A total of 96 repeat-breeder primiparous and multiparous cows were assigned among three groups: control group, inseminated and do not receive progesterone treatment; P400 and P600 groups, inseminated and received a single-intramuscular injection of 400 and 600 mg slow-release progesterone 5 days after insemination, respectively. Blood sampling was carried out on Day 20 after AI for progesterone measurement and evaluation of gene expression for ISG15, MX1 and MX2 genes. RESULTS: One injection of sustained-release progesterone increased the expression of ISG15, MX1 and MX2 genes with differences between two different progesterone concentrations. For all three genes, the level of gene expression was higher in progesterone-supplemented group than in control group, when P400 and P600 groups considered together. The level of MX2 gene expression was significantly higher in pregnant cows than non-pregnant cows. There was a significant positive correlation between expression level of all three genes and blood progesterone concentration. The expression level of ISG15 gene showed a significant positive correlation with MX1 and MX2 gene expression. CONCLUSION: The use of this sustained-release progesterone is simple and can be used in repeat-breeder cows to improve fertility.

Asunto(s)

Preparaciones de Acción Retardada , Progesterona , Animales , Progesterona/administración & dosificación , Progesterona/sangre , Bovinos/fisiología , Femenino , Interferones/genética , Interferones/metabolismo , Expresión Génica/efectos de los fármacos , Inseminación Artificial/veterinaria , Embarazo , Inyecciones Intramusculares/veterinaria

RESUMEN

The Microcystis blooms have caused serious damage to aquatic ecosystems. Microspheres containing allelochemicals with sustained-release properties have the potential to function as a cost-effective and environmentally friendly algaecide against M. aeruginosa. In the current investigation, we successfully optimized the synthesis of allelochemicals sustained-release microspheres regulated by carbon material (CM-AC@SM), which demonstrated a high embedding rate (90.17 %) and loading rate (0.65 %), with an accumulative release rate of 53.27 % on day 30. To investigate the sustained-release mechanism of CM-AC@SM, the sustained-release process of allelochemicals was determined using the Folin-Phenol method and the immersion behavior of the CM-AC@SM was characterized through SEM and XPS. Results showed that allelochemicals were released in the delayed-dissolution mode. In addition, to elucidate the synergistic mechanism of CM-AC@SM towards the inhibition of M. aeruginosa, this study comprehensively assessed the effects of allelochemicals, carbon material and CM-AC@SM on the morphology, antioxidant system activity and photosynthetic activity of M. aeruginosa. The findings indicated that allelochemicals and carbon material induced intracellular protein and nucleic acid leakage by increasing cell membrane permeability, disrupted the extracellular and intracellular morphology of algae, triggered peroxidative damage and restrained antioxidant system activity by stimulating the generation of reactive oxygen species. Simultaneously, the activity of photosystem II was inhibited by allelochemicals and carbon material, substantiated by the reduction in Fv/Fo and Fv/Fm ratios. Hence, CM-AC@SM shows promise in inhibiting M. aeruginosa, offering an efficient approach for the future large-scale control of harmful algal blooms (HABs).

Asunto(s)

Carbono , Microcystis , Microesferas , Feromonas , Microcystis/efectos de los fármacos

RESUMEN

Citrus oil (CO) is a commonly used natural flavor with high volatility, which is not conducive to sustained release under food environmental stress. This study constructed novel ß-cyclodextrin/cationic cellulose nanocrystal (ß-CD/C-CNC) complexes via noncovalent interaction, which were used to stabilize CO-loaded Pickering emulsions (PEß-CD/C-CNC). The C-CNC greatly improved the physical stability, droplet dispersion and viscoelasticity of PEß-CD/C-CNC by forming a tight network structure, as verified by rheological behavior. Moreover, C-CNC improved the wettability of ß-CD/C-CNC complexes and enhanced the interaction between adjacent ß-CD/C-CNC complexes. C-CNC also contributed to the interfacial viscoelasticity, hydrated mass, and layer thickness via the interfacial dilational modulus and QCM-D. ß-CD/C-CNC complexes adsorbed on the oil-water interface gave rise to a dense filling layer as a physical barrier, enhancing the sustained-release performance of PEß-CD/C-CNC by limiting diffusion of citrus essential oil into the headspace. This study provides new technical approaches for aroma retention in the food industry.

Asunto(s)

Celulosa , Citrus , Preparaciones de Acción Retardada , Emulsiones , Aceites Volátiles , beta-Ciclodextrinas , Emulsiones/química , Citrus/química , beta-Ciclodextrinas/química , Celulosa/química , Aceites Volátiles/química , Preparaciones de Acción Retardada/química , Reología , Viscosidad , Cationes/química , Nanopartículas/química

RESUMEN

Chronic wounds represent a serious worldwide concern, being often associated with bacterial infections. As the prevalence of bacterial infections increase, it is crucial to search for alternatives. Essential oils (EOs) constitute a promising option to antibiotics due to their strong anti-inflammatory, analgesic, antioxidant and antibacterial properties. However, such compounds present high volatility. To address this issue, a drug delivery system composed of coaxial wet-spun fibers was engineered and different EOs, namely clove oil (CO), cinnamon leaf oil (CLO) and tea tree oil (TTO), were loaded. Briefly, a coaxial system composed of two syringe pumps, a coagulation bath of deionized water, a cylindrical-shaped collector and a coaxial spinneret was used. A 10 % w/v polycaprolactone (PCL) solution was combined with the different EOs at 2 × minimum bactericidal concentration (MBC) and loaded to a syringe connected to the inner port, whereas a 10 % w/v cellulose acetate (CA) solution mixed with 10 % w/v polyethylene glycol (PEG) at a ratio of 90:10 % v/v (to increase the fibers' elasticity) was loaded to the syringe connected to the outer port. This layer was used as a barrier to pace the release of the entrapped EO. The CA's inherent porosity in water coagulation baths allowed access to the fiber's core. CA was also mixed with 10 % w/v polyethylene glycol (PEG) at a ratio of 90:10 % v/v (CA:PEG), to increase the fibers' elasticity. Microfibers maintained their structural integrity during 28 days of incubation in physiological-like environments. They also showed high elasticities (maximum elongations at break >300 %) and resistance to rupture in mechanical assessments, reaching mass losses of only ≈ 2.29 % - 57.19 %. The EOs were released from the fibers in a prolonged and sustained fashion, in which ≈ 30 % of EO was released during the 24 h of incubation in physiological-like media, demonstrating great antibacterial effectiveness against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas aeruginosa, the most prevalent bacteria in chronic wounds. Moreover, microfibers showed effective antioxidant effects, presenting up to 59 % of reduction of 2,2-diphenyl-1-picrylhydrazyl (DPPH) activity. Furthermore, the coaxial system was deemed safe for contact with fibroblasts and human keratinocytes, reaching metabolic activities higher than 80 % after 48 h of incubation. Data confirmed the suitability of the engineered system for potential therapeutics of chronic wounds.

Asunto(s)

Antioxidantes , Celulosa , Aceites Volátiles , Poliésteres , Poliésteres/química , Antioxidantes/farmacología , Antioxidantes/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Celulosa/química , Celulosa/análogos & derivados , Celulosa/farmacología , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Cicatrización de Heridas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Staphylococcus aureus/efectos de los fármacos , Escherichia coli/efectos de los fármacos

RESUMEN

Herein, we reported novel docetaxel-decorated solid lipid nanoparticle (DCT-SLN)-loaded dual thermoreversible system (DCT-DRTS) for intramuscular administration with reduced burst effect, sustained release and improved antitumor efficacy. The optimized DCT-DRTs was subjected to in-vitro and in-vivo analyses. Antitumor evaluation of the DCT-DRTS was executed and compared with DCT-hydrogel, and DCT-suspension trailed by the histopathological and immune-histochemical analyses. The DCT-SLN gave a mean particle size of 157 nm and entrapment efficiency of 93 %. It was a solid at room temperature, and changed to liquid at physiological temperature due to its melting point of about 32 °C. Unlikely, poloxamer mixture remained liquefied at 25-27 °C, however converted to gel at physiological temperature. This behavior demonstrated opposed reversible property of the DCT-SLN and poloxamer hydrogel in DCT-DRTS system, making it ideal for intramuscular administration and quick gelation inside the body. The DCT-DRTS sustained the drugs release and unlike DCT-hydrogel, the preliminary plasma concentration of DCT-DRTS was significantly reduced, overcoming the burst release. A meaningfully enhanced antitumor efficacy and improved survival rate was observed from DCT-DRTS in tumor cell xenograft athymic nude mice. Additionally, increased apoptotic and reduced proliferation markers were observed in DCT-DRTS treated tumor masses. It was concluded that DCT-DRTS may be a suitable choice for intramuscular administration of DCT with sustained release, improved bioavailability, reduced toxicity and enhanced antitumor effects.

RESUMEN

OBJECTIVE: The Port Delivery System with ranibizumab (PDS) is approved in the United States for neovascular age-related macular degeneration (nAMD). Portal (NCT03683251) is evaluating long-term safety and tolerability of the PDS in patients with nAMD who completed the phase II Ladder (NCT02510794) or phase III Archway (NCT03677934) trials. DESIGN: Multicenter, nonrandomized, open-label, extension clinical trial. PARTICIPANTS: All-PDS safety population (N = 555) comprises patients enrolled in Portal who completed Ladder or Archway. Due to data availability, efficacy population comprises Ladder-to-Portal patients only: patients who previously received PDS 10, 40, or 100 mg/ml pro re nata (as-needed [PRN]; n = 58, 62, 59, respectively) or monthly intravitreal ranibizumab 0.5-mg injections (monthly ranibizumab; n = 41) in Ladder and subsequently enrolled in Portal. METHODS: Ladder patients received PDS refill-exchanges PRN or monthly ranibizumab. Archway patients received PDS 100 mg/ml with fixed refill-exchanges every 24 weeks (PDS Q24W) or monthly ranibizumab. Once enrolled in Portal, all patients receive PDS Q24W from day 1. MAIN OUTCOME MEASURES: Ocular adverse events of special interest (AESIs); changes from baseline in best-corrected visual acuity (BCVA) and center point thickness (CPT); supplemental ranibizumab treatment between refill-exchange procedures; PDS Patient Preference Questionnaire results. RESULTS: In the All-PDS safety population (mean follow-up, 111 weeks), 137 (24.7%) patients had ≥ 1 ocular AESI; most common were cataract (11.4%), vitreous hemorrhage (6.1%), conjunctival thickening (bleb)/filtering bleb leak (6.3%). Endophthalmitis occurred in 11 of 555 (2.0%) patients. For Ladder-to-Portal patients previously treated with PDS 100 mg/ml or monthly ranibizumab, BCVA remained stable from baseline to month 48; mean (95% confidence interval) changes from baseline were 0.1 (-6.6, 6.8; n = 31) and 2.3 (-9.4, 14.1; n = 15) letters, respectively; CPT remained stable through month 48. Approximately 95% of patients did not need supplemental treatment before each refill-exchange for > 2 years since Portal enrollment. Of Ladder-to-Portal previous monthly ranibizumab patients, 92% preferred the PDS over injections. CONCLUSIONS: Interim results from Portal suggest 4-year maintenance of visual/anatomic outcomes with PDS 100 mg/ml, with the PDS preferred to monthly injections. Long-term safety profile of the PDS is well characterized.

RESUMEN

We present the development and characterization of a nasal drug delivery system comprised of a thermosensitive mucoadhesive hydrogel based on a mixture of the polymers Poloxamer 407, Poloxamer 188 and Hydroxypropyl-methylcellulose, and the psychedelic drug 5-methoxy-N,-N-dimethyltryptamine. The development relied on a 3 × 3 Box-Behnken experimental design, focusing on optimizing gelification temperature, viscosity and mucoadhesion. The primary objective of this work was to tailor the formulation for efficient nasal drug delivery. This would increase contact time between the hydrogel and the mucosa while preserving normal ciliary functioning. Following optimization, the final formulation underwent characterization through an examination of the in vitro drug release profile via dialysis under sink conditions. Additionally, homogeneity of its composition was assessed using Raman Confocal Spectroscopy. The results demonstrate complete mixing of drug and polymers within the hydrogel matrix. Furthermore, the formulation exhibits sustained release profile, with 73.76% of the drug being delivered after 5 h in vitro. This will enable future studies to assess the possibility of using this formulation to treat certain mental disorders. We have successfully developed a promising thermosensitive and mucoadhesive hydrogel with a gelling temperature of around 32 °C, a viscosity close to 100 mPas and a mucoadhesion of nearly 4.20 N·m.

RESUMEN

OBJECTIVE: This work is aimed to Formulate, Optimize and Evaluate Gastro-Retentive Microspheres of Antidiabetic Agent by Full Factorial Design. METHODS: Microspheres were prepared using Emulsification-cross linking technique. To this HPMC-K4M and Carbopol was dissolved in 250 ml of water and allowed to swell for 24 hr at room temperature. And separately chitosan was dissolved in 3% (v/v) glacial acetic acid and this also kept for 24 h to swell or dissolve properly. After 24hr this swelled mixture was mixed under magnetic stirrer (Remi, India) at specific stirring rate for 1hr in order to find homogeneous mass of both the gum. Then slurry of chitosan also was homogenized for half an hour. The drug, Glipizide (1g) was then added to the chitosan solution and mixed homogenesously. RESULTS: The aim of the study was to formulate and evaluate microspheres, for Gastro-Retentive Microspheres of the chosen drug. The EE of microspheres was found to be 91.52%, maximum . Buoyancy property observed was 93.82% for Optimized formulation F-9, Drug release 57.34% till 8 h. The work also aims to study various parameters affecting the behaviour of microspheres in oral dosage form. CONCLUSION: Drugs with short half-life that are absorbed from the gastrointestinal tract (GIT) are eliminated rapidly from the blood flow. To avoid this, the oral SR Gastro-retentive was developed as this formulation released the drug slowly into the GIT and maintained a stable drug concentration in the serum for a longer duration of time.

Asunto(s)

Quitosano , Hipoglucemiantes , Microesferas , Hipoglucemiantes/administración & dosificación , Quitosano/química , Estabilidad de Medicamentos , Preparaciones de Acción Retardada , Animales , Ratas , Glipizida/administración & dosificación , Glipizida/farmacocinética

RESUMEN

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.

Asunto(s)

Colitis , Colon , Preparaciones de Acción Retardada , Mesalamina , Micelas , Nitrorreductasas , Polímeros , Profármacos , Animales , Profármacos/química , Profármacos/farmacocinética , Mesalamina/química , Mesalamina/farmacocinética , Nitrorreductasas/metabolismo , Ratones , Colon/metabolismo , Colon/patología , Polímeros/química , Colitis/tratamiento farmacológico , Colitis/metabolismo , Preparaciones de Acción Retardada/química , NADH NADPH Oxidorreductasas/metabolismo , Ratones Endogámicos C57BL , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Masculino