Intravitreal implants for drug delivery: clinical efficacy, safety, and translational perspectives Carolina Nunes da Silva, Thomas Toshio Inoue, Marina França Dias, Silvia Ligorio Fialho, Armando Silva-Cunha Expert Opinion on Drug Delivery, 2026 INTRODUCTION: Chronic retinal disorders such as age-related macular degeneration, diabetic macular edema, retinal vein occlusion, and noninfectious uveitis are among the leading causes of irreversible visual loss worldwide. Their management depends on repeated intravitreal injections of anti-VEGF agents or corticosteroids, which, despite proven efficacy, are associated with high treatment burden and cumulative risks. Sustained-release intravitreal drug delivery systems (DDSs) are effective strategies to prolong therapeutic activity, enhance bioavailability, minimize adverse events, and improve patient adherence. AREAS COVERED: This review provides an overview of the evolution, clinical efficacy, and translational potential of intravitreal DDSs, from nonbiodegradable implants to biodegradable systems. Advances in polymeric design, hydrogels, in situ forming systems, and 3D-printed architecture, are discussed alongside emerging clinical candidates. Key formulation, preclinical, and regulatory barriers to clinical translation are also examined. Comprehensive search on PubMed, Scopus, Web of Science, ClinicalTrials.gov, and regulatory repositories was performed (data published up to December 2025). EXPERT OPINION: Intravitreal DDSs are redefining ocular pharmacotherapy by offering prolonged, localized drug release. However, further innovation in polymer design, bioerodible materials, and sterilization methods is essential to balance safety, efficacy, and manufacturability. Integration of precision medicine and next-generation biomaterials will be key to achieving fully optimized, minimally invasive retinal therapies.
Rosemary Essential Oil Microemulsion for Fungal Keratitis Treatment Saulo Ribeiro, Mariana Coelho Moraes, Denise de Oliveira Scoaris, Jovita Eugênia Gazinelli Cruz Madeira, Silvia Ligório Fialho, Carolina Paula de Souza Moreira Chemistry and Biodiversity, 2025 This study investigated the use of Rosmarinus officinalis (rosemary) essential oil in a microemulsion (ME) formulation for the treatment of ocular fungal keratitis, a serious infection that can lead to blindness. The ME was characterized in terms of pH, stability, homogeneity, osmolarity, and other physicochemical properties. The Hen's Egg Test‐Chorioallantoic Membrane assay was used to assess ocular irritancy, and antifungal efficacy was evaluated using the minimum inhibitory concentration method. The oil extraction yielded 1.2%, with eucalyptol (37.89%) as the major compound. The formulation showed a suitable pH (6.96), particle size of 11.35 nm, good stability, and was classified as non‐irritant with an irritation score = 1.5. It exhibited strong antifungal activity against Candida parapsilosis (96.1%), C. krusei (100%), C. albicans (99.1%), Fusarium graminearum (90.5%), and Aspergillus parasiticus (79.5%). The results highlight the potential of rosemary essential oil as a base for developing eye drops for the treatment of fungal keratitis.
Interlamellar keratoplasty for implantation of decellularized porcine corneal lenticule in a rabbit for corneal thickening Lays Fernanda Nunes Dourado, Fernanda Aparecida Silva Vieira, Thomas Toshio Inoue, Silvia Ligorio Fialho, Lutiana Amaral de Melo, Vinicius Viana Pereira, Juliana Rios de Simoni, Matheus Soares Siman, Paulo Ferrara de Almeida Cunha, Armando da Silva Cunha Júnior Journal of Materials Science Materials in Medicine, 2025 Changes in collagen orientation and distribution on the corneas lead to the development of diseases characterized by progressive thinning, such as keratoconus. Part of people diagnosed with keratoconus require a corneal graft, which has availability as a major limiting factor. In this scenario, new approaches have been tested to obtain substitute tissues. Porcine cornea has been receiving increasing attention due to its ease of obtaining, biomechanical properties similar to those of human tissue and lower antigenicity. Based on this, the objective of this study was to evaluate the biocompatibility of porcine stroma decellularized by sodium dodecyl sulfate (SDS) through interlamellar implantation in rabbit corneas. The obtained results showed that the lenticule intrastromal implantation was successfully performed and did not elicit rejection. Furthermore, the implanted stroma was able to promote an increase in the thickness of the host cornea. Microscopic analyses revealed that the tissue was well-adhered and the collagen fibrils were more aligned on its periphery. Therefore, it is concluded that the implantation of decellularized porcine stroma occurred satisfactorily and represents a promising alternative to replace human tissue.
Multimodal nanoparticles co-delivering bevacizumab and dichloroacetate for dual targeting of neoangiogenesis and hyperglycolysis in glioblastoma treatment Catarina Pacheco, Olaya de Dios, Maria Angeles Ramiréz-González, Cláudia Martins, Sílvia L. Fialho, Fátima Baltazar, Bruno M. Costa, Pilar Sánchez-Gómez, Bruno Sarmento Journal of Controlled Release, 2025 Glioblastoma (GBM) is a virtually incurable primary brain tumor, characterized by aggressive proliferation and sustained angiogenesis. The current anti-angiogenic treatment with systemically administered bevacizumab fails to increase patient survival. Encapsulation of bevacizumab into polymeric nanoparticles has shown promise in improving drug brain bioavailability after intranasal administration. Nevertheless, therapeutic efficacy remains limited by tumor cells adopting a hyperglycolytic metabolism. Here, we optimized BDNP, a multidrug formulation for GBM treatment, by co-entrapment of the anti-angiogenic bevacizumab and the glycolysis inhibitor dichloroacetate into poly(lactic-co-glycolic) acid nanoparticles. We then confirmed BDNP therapeutic potential through a series of in vitro and in vivo assays. BDNP preserved bevacizumab functionality, effectively inhibiting chorioallantoic membrane vascularization and endothelial cell angiogenesis fueled by GBM cell lines or patient-derived neurospheres. Moreover, BDNP successfully prevented the ∼3-fold increase in lactate production triggered by bevacizumab. Surface decoration with a CD147-targeting peptide increased BDNP retention in tumor cells in vitro by ∼10-fold, though it did not significantly improve brain accumulation in a U-251MG GBM mouse model. Regardless of decoration, nanoparticles reached and accumulated in animals' brains after intranasal administration. Intranasal administration of BDNP significantly improved a GBM mouse model survival, with no evidence of toxicity. A similar trend was observed in mice bearing patient-derived neurospheres. These findings highlight BDNP as a promising strategy for GBM therapy and establish valuable protocols for developing and validating novel multidrug nanoparticles, especially for antibodies and small molecule cocktails.
Intravitreal acetazolamide implant for pseudophakic cystoid macular edema Rodrigo Jorge, Isabela Franco Villela, Christian Fernandes, Thais Marino de Azevedo Bastos, Ingrid U. Scott, Armando da Silva Cunha, Silvia Ligório Fialho, Pedro Henrique Reis da Silva, André Messias Documenta Ophthalmologica, 2023
Licarin A as a Novel Drug for Inflammatory Eye Diseases Mayara Rodrigues Brandão de Paiva, Daniel Vítor de Vasconcelos-Santos, Márcio Matos Coelho, Renes Resende Machado, Norberto Peporine Lopes, Armando Silva-Cunha, Silvia Ligório Fialho Journal of Ocular Pharmacology and Therapeutics, 2021
Intravitreal thalidomide ameliorates inflammation in a model of experimental uveitis induced by BCG Brenda Fernanda Moreira Castro, Lorena Carla Vieira, Daniel Vitor Vasconcelos-Santos, Sarah Pereira de Freitas Cenachi, Oliver Araújo Lacerda Cotta, Maria Carolina Andrade Guerra, Mayara Rodrigues Brandão Paiva, Luciana Maria Silva, Armando Silva-Cunha, Sílvia Ligório Fialho International Immunopharmacology, 2020
Systematic evaluation of the impact of solid-state polymorphism on the bioavailability of thalidomide Guilherme Henrique Onório de Oliveira, Sara Batista do Nascimento, Flávio Martins de Oliveira, Vinícius Silva Belo, Lucas José de Alencar Danda, José Lamartine Soares-Sobrinho, Silvia Ligório Fialho, Danilo César Galindo Bedor, Whocely Victor de Castro European Journal of Pharmaceutical Sciences, 2019
Intravitreal injection of polysorbate 80: A functional and morphological study FRANCISCO MAX DAMICO, FÁBIO GASPARIN, GABRIELA LOURENÇON IOSHIMOTO, THAIS ZAMUDIO IGAMI, ARMANDO DA SILVA CUNHA JR., SILVIA LIGORIO FIALHO, ANDRE MAURICIO LIBER, LUCY HWA-YUE YOUNG, DORA FIX VENTURA Revista do Colegio Brasileiro De Cirurgioes, 2017
Development and evaluation of sustained-release etoposide-loaded poly(ε-caprolactone) implants Ana Gabriela Reis Solano, Adriana de Fátima Pereira, Flavia Carmo Horta Pinto, Letícia Gonçalves Resende Ferreira, Leandro Augusto de Oliveira Barbosa, Silvia Ligório Fialho, Patrícia Santiago de Oliveira Patricio, Armando da Silva Cunha, Gisele Rodrigues da Silva, Gérson Antônio Pianetti AAPS Pharmscitech, 2013
Polymeric delivery systems for the administration of therapeutic peptides and proteins Revista De Ciencias Farmaceuticas Basica E Aplicada, 2012
Development of clozapine tablets by direct compression - analysis of pharmaceutical equivalence by dissolution profiles Latin American Journal of Pharmacy, 2010
Evaluation of biodegradable implants based on polymer blends: Development, characterization and in vitro release studies Latin American Journal of Pharmacy, 2010
Preparation and evaluation of W/O/W multiple emulsion containing naltrexone hydrochloride: A pilot study Latin American Journal of Pharmacy, 2009
Preliminary investigation evaluating the influence of compaction and grinding process and relationship with crystalline and polymorphic properties of the thalidomide Latin American Journal of Pharmacy, 2009
