Armando da Silva Cunha Júnior

In vitro release and characterization of chitosan films as dexamethasone carrier

Chitosan, a biodegradable and biocompatible polysaccharide, is a potentially useful material in various fields. We produced mono and bilayer chitosan films containing dexamethasone as a drug carrier for controlled release. The chitosan drug-loaded films were produced by a casting/solvent evaporation technique using 2 wt% acetic acid solution and distilled water and they were dried at room temperature. These films were characterized by release and swelling studies, DSC and ATR-FTIR. The total profile for water absorption was similar for the types of films developed. ATR-FTIR analysis showed little change in the band position of the O--H and N--H stretching from dexamethasone and chitosan, respectively. DSC analysis from bilayer film indicates that the dexamethasone peak was shifted from 256 to 240 degrees C. These results suggested an interaction between hydroxyl and amino groups of chitosan and hydroxyl groups of dexamethasone. In the drug release studies it was observed 89.6% release from the monolayer film in 8h and 84% from the bilayer film in 4 weeks. These results suggested that the chitosan sheet prepared in this study is a promising delivery carrier for dexamethasone.

Microemulsões como veículo de drogas para administração ocular tópica

The conventional ophthalmic dosage forms are relatively simple: usually, water-soluble drugs are delivered in aqueous solution and water-insoluble drugs are prepared as suspensions or ointments. However, these delivery systems currently used present very low corneal bioavailability, systemic exposure because of nasolacrimal drainage and lack of efficiency in the posterior segment of ocular tissue. Recent research efforts have focused on the development of new ophthalmic drug delivery systems. As a result of these efforts, microemulsions are promising dosage forms for ocular use. These delivery systems are dispersions of water and oil that require surfactant and co-surfactant agents in order to stabilize the interfacial area. The microemulsions have a transparent appearance, thermodynamic stability and small droplet size of the dispersed fase (<1,0 mm), providing them with the capacity of being sterilized by filtration. Furthermore, these systems offer additional advantages that include: low viscosity, great ability as drug delivery vehicles, widened properties as absorption promoters and easiness of preparation, which do not require much energy and the use of special equipments. In this review, we present the technology and some preliminary studies of microemulsions in relation to ocular drug delivery systems.

Implants as drug delivery devices for the treatment of eye diseases

The treatment of diseases affecting the posterior segment of the eye is limited by the difficulty in transporting effective doses of drugs to the vitreous, retina, and choroid. Topically applied drugs are poorly absorbed due to the low permeability of the external ocular tissues and tearing. The blood-retina barrier limits drug diffusion from the systemic blood to the posterior segment, thus high doses of drug are needed to maintain therapeutic levels. In addition, systemic side effects are common. Intraocular injections could be an alternative, but the fast flowing blood supply in this region, associated with rapid clearance rates, causes drug concentration to quickly fall below therapeutic levels. To obtain therapeutic levels over longer time periods, polymeric sustained-drug release systems implanted within the vitreous are being studied for the treatment of vitreoretinal disorders. These systems are prepared using different kinds of biodegradable or non-biodegradable polymers. This review aims to demonstrate the main characteristics of these drug delivery implants and their potential for clinical application.

Implantes biodegradáveis destinados à administração intra-ocular

O tratamento de doencas oculares que acometem o vitreo e a retina tem sido um problema devido a dificuldade de penetracao das drogas no segmento posterior do bulbo ocular. A administracao de colirios apresenta efeito terapeutico minimo nessa regiao do olho, que, geralmente, e mantido com a administracao de doses frequentes do medicamento. Uma alternativa seria a injecao intra-ocular; entretanto, a rapida circulacao sanguinea nesses locais promove uma reducao da meia-vida das drogas, diminuindo, rapidamente, suas concentracoes a niveis subterapeuticos. Visando a obtencao de niveis terapeuticos adequados de drogas no segmento posterior do bulbo ocular por longos periodos, sistemas de liberacao polimericos implantados intravitreo estao sendo investigados para o tratamento de varias doencas vitreo-retinianas. Esses implantes sao preparados a partir de diferentes polimeros, os quais podem ser biodegradaveis ou nao biodegradaveis. Os polimeros derivados dos acidos latico e glicolico tem se revelados bastante promissores devido, principalmente, as suas caracteristicas de biocompatibilidade e biodegradabilidade. De acordo com os estudos realizados ate o momento, os implantes podem se apresentar na forma de bastao, de discos ou de membranas e ser obtidos pelos metodos de moldagem, de extrusao ou de preparacao de filmes. O presente artigo objetiva uma revisao de literatura abordando o tema e os principais estudos relacionados com a utilizacao de implantes polimericos como sistemas transportadores de drogas para aplicacao intra-ocular.

Polyurethanes as supports for human retinal pigment epithelium cell growth

Purpose The transplant of retinal pigment epithelium (RPE) cells on supports may well be an effective therapeutic approach to improve the visual results of patients with age-related macular degeneration. In this study, two biodegradable polyurethanes were investigated as supports for human RPE cells (ARPE-19). Methods Polyurethane aqueous dispersions based on poly(caprolactone) and/or poly(ethylene glycol) as soft segments, and isophorone diisocyanate and hydrazine as hard segments were prepared. Polyurethane films were produced by casting the dispersions and allowing them to dry at room temperature for one week. The ARPE-19 cells were seeded onto the polyurethane films and they were investigated as supports for in vitro adhesion, proliferation, and uniform distribution of differentiated ARPE-19 cells. Additionally, the in vivo ocular biocompatibility of the polyurethane films was evaluated. Results The RPE adhered to and proliferated onto the polyurethane supports, thus establishing cellPUD surface interactions. Upon confluence, the cells formed an organized monolayer, exhibited a polygonal appearance, and displayed actin filaments which ran along the upper cytoplasm. At 15 days of seeding, the occluding expression was confirmed between adjacent cells, representing the barrier functionality of epithelial cells on polymeric surfaces and the establishment of cell-cell interactions. Results from the in vivo study indicated that polyurethanes exhibited a high degree of short-term intraocular biocompatibility. Conclusions Biodegradable polyurethane films display the proper mechanical properties for an easy transscleral-driven subretinal implantation and can be considered as biocompatible supports for a functional ARPE-19 monolayer.

Controlled release of triamcinolone acetonide from polyurethane implantable devices: application for inhibition of inflammatory-angiogenesis

The purpose of this study was to develop triamcinolone acetonide-loaded polyurethane implants (TA PU implants) for the local treatment of different pathologies including arthritis, ocular and neuroinflammatory disorders. The TA PU implants were characterized by FTIR, SAXS and WAXS. The in vitro and in vivo release of TA from the PU implants was evaluated. The efficacy of TA PU implants in suppressing inflammatory-angiogenesis in a murine sponge model was demonstrated. FTIR results revealed no chemical interactions between polymer and drug. SAXS results indicated that the incorporation of the drug did not disturb the polymer morphology. WAXS showed that the crystalline nature of the TA was preserved after incorporation into the PU. The TA released from the PU implants efficiently inhibited the inflammatory-angiogenesis induced by sponge discs in an experimental animal model. Finally, TA PU implants could be used as local drug delivery systems because of their controlled delivery of TA.

Assessing the maxillary sinus mucosa of rabbits in the presence of biodegradable implants

UNLABELLED In an attempt to improve the quality of life of patients with vitreous humor disease, ophthalmologists began offering steroid-eluting biodegradable implants to their patients. These implants can be used as an alternative treatment for CRS and this is why this experimental study was carried out on rabbit maxillary sinuses. OBJECTIVE This study aims to assess the histology of the mucosa of the maxillary sinuses of rabbits after the placement of a prednisolone-eluting biodegradable implant. METHOD Eighteen rabbits were randomly divided into two groups: group 1 - subjects had drug-eluting implants placed on their left maxillary sinuses; group 2 - subjects had non-drug-eluting implants placed on their left maxillary sinuses. The right maxillary sinuses served as the controls. After seven, 14, and 28 days three rabbits in each group were randomly picked to have their tissue inflammatory response assessed. RESULTS Levels of mucosal inflammation were not significantly different between the groups with and without drug-eluting implants and the control group, or when the groups with drug-eluting implants and non-drug-eluting implants were compared. CONCLUSION Signs of toxicity or mucosal inflammation were not observed in the maxillary sinuses of rabbits given prednisolone-eluting implants or non-drug-eluting implants.

Development and validation of a high performance liquid chromatographic method for determination of cyclosporine-A from biodegradable intraocular implants

C and UV detection at 210 nm. The method provided selectivity based on resolution among peaks. It was linear over the range of 2.5-40.0 µg/mL. The quantitation and detection limits were 0.8 and 1.2 µg/mL, respectively. The recovery was 101.8% and intra-day and inter-day precision was close to 2%.

Sistemas biodegradáveis contendo acetato de prednisolona para administração orbitária

OBJETIVO: O presente estudo objetivou o desenvolvimento e a avaliacao de um sistema biodegradavel de liberacao de farmacos com caracteristica de liberacao prolongada, destinado a administracao orbitaria de acetato de prednisolona (AP). METODOS: O sistema desenvolvido, na forma de microesferas (MEs) de poli-e-caprolactona (PCL) contendo o AP, foi obtido pelo metodo de evaporacao de solvente. As MEs foram caracterizadas por microscopia eletronica de varredura (MEV), calorimetria diferencial exploratoria (DSC), avaliacao do teor de encapsulacao e pelo perfil de liberacao in vitro. O perfil de liberacao in vivo foi avaliado em coelhos apos administracao peribulbar de uma suspensao aquosa das MEs. A biocompatibilidade local do sistema foi verificada por meio de analise histopatologica da regiao de implantacao. RESULTADOS: Apos obtencao das MEs, a analise morfologica por MEV mostrou a viabilidade do metodo de obtencao do sistema. O teor de AP encapsulado foi de 43 ± 7% e pode ser considerado bastante satisfatorio. A caracterizacao do sistema por DSC, alem de confirmar a sua estabilidade, nao indicou a existencia de interacao entre o farmaco e o polimero. O estudo de liberacao in vitro indicou que o sistema apresenta perfil de liberacao prolongada. O estudo in vivo confirmou o perfil de liberacao prolongado do AP a partir das MEs, sugerindo, tambem, a viabilidade do sistema devido a ausencia de toxicidade local. CONCLUSAO: O conjunto dos resultados obtidos neste trabalho e relevante e credencia o sistema desenvolvido como uma possivel alternativa ao tratamento de orbitopatias inflamatorias.

Osteogenic differentiation of adipose-derived stem cells in mesoporous SBA-16 and SBA-16 hydroxyapatite scaffolds

Adipose-derived stem cells (ASCs) are currently a point of focus for bone tissue engineering applications. In this study, a biomaterial (HA-SBA-16) has been developed based on the growth of calcium phosphate (HA) particles within an organized silica structure (SBA-16) to evaluate their application in the osteogenic differentiation process. Indeed, pure SBA-16 was used to compare the effect of structural characteristics on the biological application. The samples were characterized by N2 Adsorption, transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) and thermal analysis. In vitro assays were performed to evaluate the viability, cytotoxicity and biological behavior of the ASCs on SBA-16 and HA/SBA-16 nanocomposites to verify their potential as bioactive materials for applications in bone-tissue engineering. The differentiation capacity of the ASCs seeded in SBA-16 and HA/SBA-16 was confirmed by the induction of the increase in AP production/activity of the ASCs, the expression of osteogenic gene markers (type I collagen mRNA, osteopontin and osteocalcin), and functionally, by Von Kossa staining. The results showed that those compositions have beneficial effects in stem cells, maintaining cell viability and allowing/promoting osteogenic differentiation.