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3PC-015 Development of injectable hydroxocobalamin microcapsules for the treatment of homocystinuria and methylmalonic aciduria

ejhpharm · 2026-03-18 · canonical JSON source

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Background and Importance Methylmalonic acidemia with homocystinuria type CblC is a severe, congenital disorder caused by a defect in vitamin B12 metabolism. Treatment with hydroxocobalamin improves some symptoms but has limited effectiveness on ocular structures due to its poor permeability through the blood-ocular barrier. This results in blindness in most patients, and topical treatment is ineffective due to poor corneal absorption. Despite treatment, patients often suffer a reduced quality of life.Aim and Objectives In this project, a formulation is exposed to solve this problem. The formulation consists of a suspension of drug-loaded microcapsules of PEOT/PBT polymer for extended release by intravitreal administration.Material and Methods The methodology used to make the microcapsules was double emulsion-solvent evaporation using ultrasound. The emulsion was W/O/W sign. The microparticles presented an aqueous core with hydroxocobalamin and a sustained release polymeric shell.Scanning electron microscopy (SEM) was performed to verify the homogeneity of the outer shell. To obtain microcapsules with an adequate release profile, a rotational mathematical design consisting of 23 different tests and an ANOVA analysis was carried out. The intention was to maximise size homogeneity and encapsulation performance.Results The results showed a maximum microcapsule load, better release profile, and greater homogeneity with a lower weight polymer and intermediate agitation speed. Further studies will be needed to assess the in vivo ocular viability of the formulation.Conclusion and Relevance The studies carried out to date indicate that microcapsules have potential in the ocular treatment of this disease. Although the findings are not discouraging, much more evidence is needed to bring this formulation to the clinical setting. It would be interesting to perform longer release profiles and in vivo tests.References and/or Acknowledgements 1. Rickes EL, Brink NG, Koniuszy FR, Wood TR, Folkers K. Crystalline vitamin B12. Science. 16 de abril de 1948;107(2781):396–7.2. Wang Y, Liu C, Fan L, Sheng Y, Mao J, Chao G, et al. Synthesis of biodegradable poly(butylene terephthalate)/poly(ethylene glycol) (PBT/PEG) multiblock copolymers and preparation of indirubin loaded microspheres. Polym Bull. 1 de enero de 2005;53(3):147–54.3. Cuello-Rodríguez S, Blanco-Fernández G, García-Otero X, Díaz-Tome V, Otero-Espinar FJ, Seoane-Viaño I. Long acting injectables & implants: advances in intraocular drug delivery. Int J Pharm. 2025 Oct 15;683:126058. doi: 10.1016/j.ijpharm.2025.126058.Conflict of Interest No conflict of interest