Endophthalmitis, an inflammation of the eye due to perioperative infection, may occur after cataract surgery. Intraocular lenses (IOLs) loaded with an antibiotic have been proposed as an alternative to the conventional postoperative endophthalmitis prophylaxis, since the antibiotic is delivered directly to the target site. In this work, an IOL-based antibiotic releasing system was prepared from a copolymer used in the production of IOLs and a fluoroquinolone used in endophthalmitis prophylaxis (moxifloxacin, MFX). Argon plasma-assisted grafting with 2-hydroxyethyl methacrylate (HEMA) in the presence of MFX was the approach selected for surface modification, with MFX loaded both by entrapment in the grafted polyHEMA coating and by soaking. Surface and bulk properties were evaluated before and after surface modification and the MFX release profiles were obtained both in batch mode (sink conditions) and under hydrodynamic conditions, employing a purpose-built microfluidic cell, which simulated the hydrodynamic conditions around the eye lens. The effect of storage on the release profile of the best system was also assessed. The best system released MFX for ca. 15 days above the minimum inhibitory concentration for Staphylococcus aureus and Staphylococcus epidermidis. The released MFX showed antimicrobial activity against these bacteria and was non-cytotoxic against corneal endothelial cells.

Intraocular lenses (IOLs) present an alternative for extended, local drug delivery in the prevention of post-operative acute endophthalmitis. In the present work, we modified the surface of a hydrophilic acrylic material, used for manufacturing of IOLs, through plasma-assisted grafting copolymerization of 2-acrylamido-2-methylpropane sulfonic acid (AMPS) or [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (SBMA), with the aim of achieving a controlled and effective drug release. The material was loaded with moxifloxacin (MFX), a commonly used antibiotic for endophthalmitis prevention. The characterization of the modified material showed that relevant properties, like swelling capacity, wettability, refractive index and transmittance, were not affected by the surface modification. Concerning the drug release profiles, the most promising result was obtained when AMPS grafting was done in the presence of MFX. This modification led to a higher amount of drug being released for a longer period of time, which is a requirement for the prevention of endophthalmitis. The material was found to be non-cytotoxic for rabbit corneal endothelial cells. In a second step, prototype IOLs were modified with AMPS and loaded with MFX as previously and, after sterilization and storage (30 days), they were tested under dynamic conditions, in a microfluidic cell with volume and renovation rate similar to the eye aqueous humour. MFX solutions collected in this assay were tested against Staphylococcus aureus and Staphylococcus epidermidis and the released antibiotic proved to be effective against both bacteria until the 12th day of release.

O herpesvírus simples (HSV) é um importante problema de saúde pública em vários países provocando ulceração genital. Dentre o arsenal terapêutico para o tratamento da infecção por HSV destaca-se o aciclovir (ACV). No entanto, este apresenta limitações no seu uso como um tempo de meia-vida curto e uma baixa solubilidade aquosa. A curcumina (CUR) é um composto natural que vem demonstrando diversas atividades terapêuticas, dentre estas a atividade antiviral, porém o seu uso por via oral também é comprometido pela baixa solubilidade em água. A encapsulação em micropartículas poliméricas (MPs) é uma abordagem farmacotécnica que podem superar as dificuldades do uso terapêutico destes dois compostos. Em vista disto, o presente trabalho visou desenvolver e caracterizar MPs pelo método de aspersão compostas por HPMC e Eudragit® RS100 como materiais poliméricos, além de manitol como adjuvante de secagem. Os resultados demonstraram que o método de preparo por aspersão (spray drying) apresentou um rendimento em torno de 50% para todas as formulações desenvolvidas, mostrando um fluxo tecnológico mais vantajoso para as partículas sem manitol. O doseamento demonstrou teores de 82 a 99% e de 81 a 94%, para ACV e CUR, respectivamente. A análise granulométrica mostrou micropartículas de tamanho micrométrico entre 8,7 e 15,3 μm. A análise morfológica evidenciou o formato esférico e confirmou o resultado das análises de tamanho. A espectroscopia na região do infravermelho mostrou uma sobreposição dos espectros obtidos pelos componentes isolados indicando boa compatibilidade entre os materiais. O perfil de liberação in vitro permitiu observar que as MPs foram capazes de controlar a liberação e melhorar a solubilidade dos compostos, destacando-se, neste quesito, as MPs compostas por HPMC. A avaliação preliminar da atividade antiviral in vitro demonstrou que a associação de ACV e CUR possui um efeito sinérgico frente ao vírus BoVH-1, sendo que as MPs foram capazes de potencializar este efeito. Neste contexto, as MPs mostraram-se sistemas promissores para a veiculação de ACV e CUR por via oral, com elevado potencial para constituir um tratamento alternativo para o herpes viral.

Dispositivos de liberação controlada de fármacos objetivam principalmente minimizar a necessidade de doses tóxicas e prover um melhor controle da liberação do princípio ativo ao longo do tempo de tratamento. O Naproxeno® é um antiinflamatório não esteroidal (AINE), analgésico e antipirético, usado para o tratamento de doenças reumáticas e processos inflamatórios agudos. Em tal contexto, o referido trabalho objetivou a obtenção de biofilmes de quitosana para liberação controlada de Naproxeno®. Os filmes foram preparados pelo método de evaporação de solvente, através da dissolução da quitosana em ácido acético (1% v/v), para uma concentração final da solução polimérica (1% m/v), seguida da incorporação de Naproxeno® (0,1 mg/ml). A quitosana foi analisada quanto ao seu grau de desacetilação, já o Naproxeno® foi avaliado quantitativamente o princípio ativo presente em cada comprimido. Após a obtenção, os biofilmes foram caracterizados por meio de análises de grau de cristalinidade, difratômetro de raios X (DRX), espectroscopia na região do ultravioleta-visível (UV-Vis), permeabilidade de vapor d’água, perfil de liberação, dissolução, além do teste de tração e espessura do filme. No ensaio de DRX, observou-se que a incorporação do fármaco na solução de quitosana possibilitou a redução da cristalinidade da membrana. No ensaio de liberação, foi evidenciado que a quitosana exerceu papel fundamental na modulação do perfil de liberação do fármaco, possibilitando a detecção do Naproxeno® e indicando ser promissor no desenvolvimento de biofilmes para serem usados como dispositivos de liberação controlada de fármacos. Destaca-se também que os biofilmes apresentaram propriedades de tensão, não compatíveis e adequados para serem usados como dispositivos para liberação controlada de fármacos. Os resultados da dissolução demonstraram que o material tem caráter hidrofílico. Mediante o exposto, conclui-se que o sistema apresentou homogeneidade e adequada interação química entre os constituintes e foi possível obter biofilmes à base de quitosana para liberação controlada de Naproxeno®.

Interpolyelectrolyte complexes, which constitute a type of polymeric material obtained through the selfassembly of oppositely charged polymers, exhibit interesting properties for use in the design of smart matrices for drug delivery. In the present study, a stoichiometric interpolyelectrolyte complex (SIPEC) composed of Eudragit E® and Eudragit® L100 was obtained at pH 6.0 and characterized and evaluated as a hydrophilic matrix for dexibuprofen. The formation of a SIPEC was monitored by ζ-potential measurements and characterized using infrared spectroscopy, thermal analysis, and scanning electron microscopy. The results indicated that a SIPEC obtained under these conditions can be used as a matrix for controlling the release of dexibuprofen and exhibit a pH-triggered release.

Effective management of wounds is essential for preventing infections and promoting skin regeneration. Despite significant technological advances, many commercially available dressings exhibit limitations in exudate absorption, traumatic removal, and antimicrobial efficacy. In this context, polysaccharides have emerged as promising materials for the development of bioactive dressings, owing to their biocompatibility, biodegradability, and ability to form flexible films. This dissertation aimed to develop starch-based dressings plasticized with glycerol and doped with cationic porphyrins (TMePyP and TPPh3PyP), with the goal of combining suitable structural characteristics with antimicrobial photodynamic activity. The films were prepared by solvent casting and characterized in terms of physicochemical (thickness, wettability, residual moisture content, solubility, and singlet oxygen generation), mechanical (tensile strength, Young’s modulus, and elongation at break), and biological properties (antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa). Furthermore, the leaching behavior of the porphyrins in aqueous and biological media evaluated to support the interpretation of the biological performance results. The results obtained demonstrated that films doped with TMePyP exhibited greater flexibility, adequate wettability, and rapid release of the compound, suggesting potential applicability in the treatment of acute infections. Conversely, films with TPPh3PyP higher mechanical strength, lower solubility, and a more sustained release profile, features that may be advantageous for managing chronic infections. Films doped with porphyrins showed a high capacity for singlet oxygen generation under visible light irradiation and to significantly reduce bacterial viability in antimicrobial photodynamic therapy assays. These findings support the potential of these materials as promising photoactive platforms for antimicrobial wound dressings, adaptable to various clinical scenarios.

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed.

Microencapsulation of the therapeutical monoclonal antibody infliximab (INF) was investigated as an innovative approach to improve its stability and to achieve formulations with convenient features for intra-articular administration. Ultrasonic atomization (UA), a novel alternative to microencapsulate labile drugs, was compared with the conventional emulsion/evaporation method (Em/Ev) using biodegradable polymers, specifically Polyactive® 1000PEOT70PBT30 [poly(ethylene-oxide-terephthalate)/poly(butylene-terephthalate); PEOT-PBT] and its polymeric blends with poly-(D, L-lactide-co-glycolide) (PLGA) RG502 and RG503 (PEOT-PBT:PLGA; 65:35). Six different formulations of spherical core–shell microcapsules were successfully developed and characterized. The UA method achieved a significantly higher encapsulation efficiency (69.7–80.25%) than Em/Ev (17.3–23.0%). Mean particle size, strongly determined by the microencapsulation method and to a lesser extent by polymeric composition, ranged from 26.6 to 49.9 µm for UA and 1.5–2.1 µm for Em/Ev. All formulations demonstrated sustained INF release in vitro for up to 24 days, with release rates modulated by polymeric composition and microencapsulation technique. Both methods preserved INF biological activity, with microencapsulated INF showing higher efficacy than commercial formulations at comparable doses regarding bioactive tumor necrosis factor-alpha (TNF-α) neutralization according to WEHI-13VAR bioassay. Microparticles’ biocompatibility and extensive internalization by THP-1-derived macrophages was demonstrated. Furthermore, high in vitro anti-inflammatory activity was achieved after treatment of THP-1 cells with INF-loaded microcapsules, significatively reducing in vitro production of TNF-α and interleucine-6 (Il-6).

In this work we report the synthesis of polyurea microcapsules loaded with corrosion inhibitor 2 mercaptobenzothiazole (MBT) for corrosion protection of 2024 aluminum alloy. The microcapsules were prepared by interfacial polycondensation. The resulting capsules exhibit spherical shape, with diameter ranging between 100 nm and 2 lm. The loading content of MBT was found to be 5 wt% and release studies showed that MBT is preferentially released under acidic and alkaline conditions and follows a Fickian dif fusion model. This pH dependency seems suitable for protection of metallic alloys where corrosion pro cesses are accompanied by local pH changes. Furthermore, the microcapsules were added to a hybrid sol gel coating and its performance assessed by electrochemical and accelerated standard tests. The results obtained indicate that capsules loaded with MBT do not affect negatively the barrier properties of sol gel coatings, and contribute for the enhancement of adhesion of coatings to the metallic substrate. More rele vant, these additives impart active corrosion protection suppressing corrosion activity at defect sites, which opens prospects for application of polyurea microcapsules as additives for high performance coatings.