Trojan Microparticles Potential for Ophthalmic Drug Delivery

The administration of drugs to treat ocular disorders still remains a technological challenge in this XXI century. Although there is an important arsenal of active molecules useful to treat ocular diseases, ranging from classical compounds to biotechnological products, currenty, no ideal delivery system is able to profit all their therapeutic potential. Among the intraocular drug delivery systems (IODDS) proposed to overcome some of the most important limitations, microsystems and nanosystems have raised high attention. While microsystems are able to offer long-term release after intravitreal injection, nanosystems can protect the active compound from external environment (reducing their clearance) and direct it to its target tissues. In recent years, some researchers have explored the possibility of combining micro and nanosystems in “nanoparticle-in-microparticle (NiMs)” systems or “trojan systems”. This excellent idea is not exempt of technological problems, remains partially unsolved, especially in the case of IODDS. The objective of the present review is to show the state of art concerning the design, preparation and characterization of trojan microparticles for drug delivery and to remark their potential and limitations as IODDS, one of the most important challenges faced by pharmaceutical technology at the moment

The Use of Mucoadhesive Polymers to Enhance the Hypotensive Effect of a Melatonin Analogue, 5-MCA-NAT, in Rabbit Eyes

Purpose.: 5-Methoxy-carbonylamino-N-acetyltryptamine (5-MCA-NAT, a melatonin receptor agonist) produces a clear intraocular pressure (IOP) reduction in New Zealand White rabbits and glaucomatous monkeys. The goal of this study was to evaluate whether the hypotensive effect of 5-MCA-NAT was enhanced by the presence of cellulose derivatives, some of them with bioadhesive properties, as well as to determine whether these formulations were well tolerated by the ocular surface. Methods.: Formulations were prepared with propylene glycol (0.275%), carboxymethyl cellulose (CMC, 0.5% and 1.0%) of low and medium viscosity and hydroxypropylmethyl cellulose (0.3%). Quantification of 5-MCA-NAT (100 μM) was assessed by HPLC. In vitro tolerance was evaluated by the MTT method in human corneal-limbal epithelial cells and normal human conjunctival cells. In vivo tolerance was analyzed by biomicroscopy and specular microscopy in rabbit eyes. The ocular hypotensive effect was evaluated measuring IOP for 8 hours in rabbit eyes. Results.: All the formulations demonstrated good in vitro and in vivo tolerance. 5-MCA-NAT in CMC medium viscosity 0.5% was the most effective at reducing IOP (maximum IOP reduction, 30.27%), and its effect lasted approximately 7 hours. Conclusions.: The hypotensive effect of 5-MCA-NAT was increased by using bioadhesive polymers in formulations that are suitable for the ocular surface and also protective of the eye in long-term therapies. The use of 5-MCA-NAT combined with bioadhesive polymers is a good strategy in the treatment of ocular hypertension and glaucoma

Block copolypeptide nanoparticles for the delivery of ocular therapeutics

Self-assembling block copolypeptides were prepared by sequential ring-opening polymerization of N-carboxyanhydride (NCA) derivatives of γ-benzyl-L-glutamic acid and ε-carbobenzyloxy-L-lysine, followed by selective deprotection of the benzyl glutamate block. The synthesized polymers had number average molecular weights close to theoretical values, and had low dispersities (ĐM = 1.15–1.28). Self-assembly of the amphiphilic block copolymers into nanoparticles was achieved using the “solvent-switch” method, whereby the polymer was dissolved in THF and water and the organic solvent removed by rotary evaporation. The type of nanostructures formed varied from spherical micelles to a mixture of spherical and worm-like micelles, depending on copolymer composition. The spherical micelles had an average diameter of 43 nm by dynamic light scattering, while the apparent diameter of the mixed phase system was around 200nm. Reproducibility of nanoparticle preparation was demonstrated to be excellent; almost identical DLS traces were obtained over three repeats. Following qualitative dye-solubilization experiments, the nanoparticles were loaded with the ocular anti-inflammatory drug dexamethasone. Loading efficiency of the nanoparticles was 90% and the cumulative drug release was 94% over 16 d, with a 20% burst release in the first 24 h.mabi201400471-gra-000

Posterior Segment Ophthalmic Drug Delivery: Role of Muco-Adhesion with a Special Focus on Chitosan.

Posterior segment eye diseases (PSEDs) including age macular degeneration (AMD) and diabetic retinopathy (DR) are amongst the major causes of irreversible blindness worldwide. Due to the numerous barriers encountered, highly invasive intravitreal (IVT) injections represent the primary route to deliver drugs to the posterior eye tissues. Thus, the potential of a more patient friendly topical route has been widely investigated. Mucoadhesive formulations can decrease precorneal clearance while prolonging precorneal residence. Thus, they are expected to enhance the chances of adherence to corneal and conjunctival surfaces and as such, enable increased delivery to the posterior eye segment. Among the mucoadhesive polymers available, chitosan is the most widely explored due to its outstanding mucoadhesive characteristics. In this review, the major PSEDs, their treatments, barriers to topical delivery, and routes of topical drug absorption to the posterior eye are presented. To enable the successful design of mucoadhesive ophthalmic drug delivery systems (DDSs), an overview of mucoadhesion, its theory, characterization, and considerations for ocular mucoadhesion is given. Furthermore, chitosan-based DDs that have been explored to promote topical drug delivery to the posterior eye segment are reviewed. Finally, challenges of successful preclinical to clinical translation of these DDSs for posterior eye drug delivery are discussed

Hybrid Formulations of Liposomes and Bioadhesive Polymers Improve the Hypotensive Effect of the Melatonin Analogue 5-MCA-NAT in Rabbit Eyes

For the treatment of chronic ocular diseases such as glaucoma, continuous instillations of eye drops are needed. However, frequent administrations of hypotensive topical formulations can produce adverse ocular surface effects due to the active substance or other components of the formulation, such as preservatives or other excipients. Thus the development of unpreserved formulations that are well tolerated after frequent instillations is an important challenge to improve ophthalmic chronic topical therapies. Furthermore, several components can improve the properties of the formulation in terms of efficacy. In order to achieve the mentioned objectives, we have developed formulations of liposomes (150–200 nm) containing components similar to those in the tear film and loaded with the hypotensive melatonin analog 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT, 100 µM). These formulations were combined with mucoadhesive (sodium hyaluronate or carboxymethylcellulose) or amphiphilic block thermosensitive (poloxamer) polymers to prolong the hypotensive efficacy of the drug. In rabbit eyes, the decrease of intraocular pressure with 5-MCA-NAT-loaded liposomes that were dispersed with 0.2% sodium hyaluronate, 39.1±2.2%, was remarkably higher compared to other liposomes formulated without or with other bioadhesive polymers, and the effect lasted more than 8 hours. According to the results obtained in the present work, these technological strategies could provide an improved modality for delivering therapeutic agents in patients with glaucoma.Fil: Quinteros, Daniela Alejandra. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vicario de la Torre, Marta. Universidad Complutense de Madrid; EspañaFil: Andrés Guerrero, Vanessa. Universidad Complutense de Madrid; EspañaFil: Palma, Santiago Daniel. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Allemandi, Daniel Alberto. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Herrero Vanrell, Rocío. Universidad Complutense de Madrid; EspañaFil: Molina Martinez, Irene T.. Universidad Complutense de Madrid; Españ

The potential of using biodegradable microspheres in retinal diseases and other intraocular pathologies

Pathologies affecting the posterior segment are one of the major causes of blindness in developed countries and are becoming more prevalent due to the increase in society longevity. Sucessful therapy of diseases affecting the back of the eye requires effective concentrations of the active substance mantained during a long period of time in the intraocular target site. Treatment of vitreoretinal diseases often include repeated intravitreous injections that are associated with adverse effects. Local administration of biodegradable microspheres offers an excellent alternative to multiple administrations, as they are able to deliver the therapeutic molecule in a controlled fashion. Furthermore, injection of microparticles is performed without the need for surgical procedures. As most of the retinal diseases are multifactorial, microspheres result especially promising because they can be loaded with more than one active substance and complemented with the inclusion of additives with pharmacological properties. Personalized therapy can be easily achieved by changing the amount of administered microspheres. Contrary to non-biodegradable devices, biodegradable PLA and PLGA microspheres disappear from the site of administration after delivering the drug. Furthermore, microspheres prepared from these mentioned biomaterials are well tolerated after periocular and intravitreal injections in animals and humans. After injection, PLA and PLGA microspheres suffer aggregation behaving like an implant. Biodegradable microspheres are potential tools in regenerative medicine for retinal repair. According to the reported results, presumably a variety of microparticulate formulations for different ophthalmic therapeutic uses will be available in the clinical practice in the near future

Programa de promoción y prevención del cuidado de la salud mental en adulto mayor en condición de vulnerabilidad

El adulto mayor es considerado como toda persona que abarca la edad de 60 años en adelante, además de haber cumplido por ciertas etapas de autorrealización tanto a nivel social, psicológico, económico y salud. Así como el adulto mayor experimenta una serie de etapas en su vida, después de estar en etapa de la vejez, empieza a vivir una serie de problemas a nivel psicológico, físico y social, a raíz de que es una de la población mas olvidada por la sociedad a causa de sus limitaciones y eso los hace vulnerable debido a que pueden llegar a experimentar maltrato físico, psicoemocional, abandono, etc. Que pone en riesgo su bienestar y desarrollo. A raíz de todo esto, surge el propósito de crear un programa para la promoción y prevención del cuidado de la salud mental del adulto mayor mediante distintas estrategias que incrementen su mejora tanto a nivel emocional como físico.The older adult is considered as any person who covers the age of 60 years onwards, in addition to having completed certain stages of self-realization both at a social, psychological, economic and health level. Just as the older adult experiences a series of stages in his life, after being in the old age stage, he begins to experience a series of problems at the psychological, physical and social level, as a result of the fact that he is one of the most forgotten population by society because of their limitations and that makes them vulnerable because they can experience physical, psycho-emotional abuse, abandonment, etc. That puts their well-being and development at risk. As a result of all this, the purpose arises to create a program for the promotion and prevention of mental health care for the elderly through different strategies that increase their improvement both emotionally and physically

Microspheres as intraocular therapeutic tools in chronic diseases of the optic nerve and retina

Pathologies affecting the optic nerve and the retina are one of the major causes of blindness. These diseases include age-related macular degeneration (AMD), diabetic Retinopathy (DR) and glaucoma, among others. Also, there are genetic disorders that affect the retina causing visual impairment. The prevalence of neurodegenerative diseases of the posterior segment are increased as most of them are related with the elderly. Even with the access to different treatments, there are some challenges in managing patients suffering retinal diseases. One of them is the need for frequent interventions. Also, an unpredictable response to therapy has suggested that different pathways may be playing a role in the development of these diseases. The management of these pathologies requires the development of controlled drug delivery systems able to slow the progression of the disease without the need of frequent invasive interventions, typically related with endophthalmitis, retinal detachment, ocular hypertension, cataract, inflammation, and floaters, among other. Biodegradable microspheres are able to encapsulate low molecular weight substances and large molecules such as biotechnological products. Over the last years, a large variety of active substances has been encapsulated in microspheres with the intention of providing neuroprotection of the optic nerve and the retina. The purpose of the present review is to describe the use of microspheres in chronic neurodegenerative diseases affecting the retina and the optic nerve. The advantage of microencapsulation of low molecular weight drugs as well as therapeutic peptides and proteins to be used as neuroprotective strategy is discussed. Also, a new use of the microspheres in the development of animal models of neurodegeneration of the posterior segment is described

Gelatin Nanoparticles-HPMC Hybrid System for Effective Ocular Topical Administration of Antihypertensive Agents

The increment in ocular drug bioavailability after topical administration is one of the main challenges in pharmaceutical technology. For several years, different strategies based on nanotechnology, hydrogels or implants have been evaluated. Nowadays, the tolerance of ophthalmic preparations has become a critical issue and it is essential to the use of well tolerated excipients. In the present work, we have explored the potential of gelatin nanoparticles (GNPs) loaded with timolol maleate (TM), a beta-adrenergic blocker widely used in the clinic for glaucoma treatment and a hybrid system of TM-GNPs included in a hydroxypropyl methylcellulose (HPMC) viscous solution. The TM- loaded nanoparticles (mean particle size of 193 ± 20 nm and drug loading of 0.291 ± 0.019 mg TM/mg GNPs) were well tolerated both in vitro (human corneal cells) and in vivo. The in vivo efficacy studies performed in normotensive rabbits demonstrated that these gelatin nanoparticles were able to achieve the same hypotensive effect as a marketed formulation (0.5% TM) containing a 5-fold lower concentration of the drug. When comparing commercial and TM GNPs formulations with the same TM dose, nanoparticles generated an increased efficacy with a significant (p < 0.05) reduction of intraocular pressure (IOP) (from 21% to 30%) and an augmentation of 1.7-fold in the area under the curve (AUC)(0–12h). On the other hand, the combination of timolol-loaded nanoparticles (TM 0.1%) and the viscous polymer HPMC 0.3%, statistically improved the IOP reduction up to 30% (4.65 mmHg) accompanied by a faster time of maximum effect (tmax = 1 h). Furthermore, the hypotensive effect was extended for four additional hours, reaching a pharmacological activity that lasted 12 h after a single instillation of this combination, and leading to an AUC(0 12h) 2.5-fold higher than the one observed for the marketed formulation. According to the data presented in this work, the use of hybrid systems that combine well tolerated gelatin nanoparticles and a viscous agent could be a promising alternative in the management of high intraocular pressure in glaucoma

Fatores que influenciam o ensino técnico-stress durante a pandemia de COVID-19 em Equador

Introduction: the use of Information and Communications Technology (ICT) is an indispensable tool for the continuous distance teaching-learning process. Technostress is the result of the individual inability of a person to adapt normally to the use of new technologies within their work activities. Objective: to identify the stress factors associated with the use of ICT in primary and secondary education teachers in the context of the COVID-19 pandemic (November 2021 and January 2022), in Santo Domingo de los Colorados, Ecuador. There was implemented the complete closure of schools as a sanitary measure. Method: a study of quantitative approach of correlational scope and transactional design, applied to 485 teachers of fiscal and private educational units, to whom a questionnaire of 20 questions was applied, that measured different factors, such as: skepticism about the use of ICT, work fatigue, anxiety and inefficiency. The results of the study were statistically analyzed through Exploratory Factor Analysis (EFA), Confirmatory Factor Analysis (CFA) and Structural Equation Modeling (SEM); developed in SPPS 20 and AMOS 24. Results: through the estimates thrown in the AMOS Output, we obtained: skepticism (β=0.327), work fatigue (β=0.238), anxiety (β=0.394) and inefficiency (β=0.010). Conclusions: it was possible to show that skepticism, work fatigue and anxiety are influential factors in the presence of teaching technostress, while inefficiency is not. These aspects will serve as a basis for the formulation of strategies and measures that allow the effective and sustainable integration of ICTs in the educational field.Introducción: el uso de las Tecnologías de la Información y las Comunicaciones (TIC) es herramienta indispensable para el continuo proceso de enseñanza-aprendizaje a distancia. El tecnoestrés es la resultante de la incapacidad individual que tiene una persona para adaptarse con normalidad al uso de las nuevas tecnologías dentro de sus actividades laborales. Objetivo: identificar los factores de estrés asociados al uso de las TIC en docentes de educación primaria y secundaria en el contexto de la pandemia COVID-19 (noviembre de 2021 a enero de 2022), en Santo Domingo de los Tsáchilas, Ecuador, donde se implementó el cierre completo de escuelas como medida sanitaria. Método: estudio de enfoque cuantitativo de alcance correlacional y diseño transeccional, aplicado a 485 profesores de unidades educativas fiscales y particulares a quienes se les aplicó un cuestionario de 20 preguntas que midieron factores, como: escepticismo al uso de las TIC, fatiga laboral, ansiedad e ineficacia. Los resultados del estudio fueron analizados estadísticamente a través de un Análisis Factorial Exploratorio (AFE), Análisis Factorial Confirmatorio (AFC) y Modelado de Ecuaciones Estructurales (MEE); desarrollados en SPPS 20 y AMOS 24.Resultados: a través de los estimados arrojados en el AMOS Output, se obtuvo: escepticismo (β=0,327), fatiga laboral (β=0,238), ansiedad (β=0,394) e ineficacia (β=0,010). Conclusiones: se pudo evidenciar que el escepticismo, la fatiga laboral y la ansiedad son factores influyentes en la presencia de tecnoestrés docente, mientras que la ineficacia no lo es; dichos aspectos servirán como base para la formulación de estrategias y medidas que permitan la integración efectiva y sostenible de las TIC en el ámbito educativo.Introdução: a utilização das TIC é uma ferramenta indispensável para o processo contínuo de ensino-aprendizagem a distância. O technostress é o resultado da incapacidade individual que uma pessoa tem de se adaptar normalmente ao uso de novas tecnologias dentro de suas atividades laborais. Objetivo: identificar os fatores de estresse associados ao uso das TIC em professores do ensino fundamental e médio no contexto da pandemia de COVID-19 (novembro de 2021 a janeiro de 2022), em Santo Domingo de los Tsáchilas, Equador, onde o fechamento de escolas foi implementado como medida sanitária.Método: estudo de abordagem quantitativa de abrangência correlacional e desenho transacional, aplicado a 485 professores de unidades educacionais públicas e privadas que receberam um questionário de 20 questões que mensurava fatores como: ceticismo quanto ao uso das TIC, cansaço no trabalho, ansiedade e ineficiência. Os resultados do estudo foram analisados estatisticamente por meio de Análise Fatorial Exploratória (AFE), Análise Fatorial Confirmatória (AFC) e Modelagem de Equações Estruturais (MEV); desenvolvido no SPPS 20 e AMOS 24. Resultados: através das estimativas lançadas no AMOS Output, obtivemos: ceticismo (β=0,327), fadiga no trabalho (β=0,238), ansiedade (β=0,394) e ineficiência (β=0,010). Conclusões: foi possível evidenciar que o ceticismo, o cansaço no trabalho e a ansiedade são fatores influentes na presença do tecnoestresse docente, enquanto a ineficiência não o é; Esses aspectos servirão de base para a formulação de estratégias e medidas que permitam a integração efetiva e sustentável das TICs no campo educacional