Abstract
In commercial applications, sofosbuvir (SOF) for hepatitis C is only available in tablet dosage form, resulting in minimal SOF accumulation in the liver (26.94%) due to its low intestinal permeability and high molecular weight (529.5 Da). Therefore, in this study, luminar capsule microneedles (LUCAMs) were developed, in which SOF was delivered via dissolving microneedles (DMN) attached to a branch and encapsulated in an enteric-coated hard capsule designed to dissolve exclusively in the intestinal environment. The needle on the DMN has the potential to facilitate SOF absorption in the intestine, thereby enabling maximum absorption. A thorough evaluation of DMN, branches, and capsules was conducted, encompassing formulation, characterization, differential scanning calorimetry, and dissolution time. This comprehensive evaluation demonstrated that the results obtained align with the established specifications.
Furthermore, a series of evaluations, including capsule coating, revealed that the capsules dissolve selectively under intestinal pH conditions, as indicated by a hemolysis assay and irritation potential levels below 5%. These findings collectively demonstrate that the utilized biomaterial is nontoxic and nonirritating. In vitro and ex vivo permeability studies demonstrated that LUCAMs released 99.32 ± 11.92 and 203.97 ± 19.78 μg/mL SOF within 24 h, respectively.
In vivo studies were conducted on two groups, namely, LUCAMs and controls, with measurements taken at 12, 24, and 36 h. The results demonstrated a significant increase in SOF concentration in the liver, reaching 1.26 ± 0.18 μg/mL in the LUCAM group by 36 h, in contrast to the control group, which was only detected at 12 h (0.83 ± 0.13 μg/mL) and not detected at 24 and 36 h. Histopathological analysis confirmed the absence of severe tissue damage, indicating that LUCAMs are a promising approach for enhancing the delivery of SOF to the liver and improving the efficacy of hepatitis C treatment.
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Musyfira Sahra, Nurul Fitrayani, Abigael Alik Samma, Christopher Kosasi Ko, Felicia Virginia Thios, and Andi Dian Permana, Application of Biomaterials in the Development of Enteric-Coated Luminar Capsule Microneedles for Selective Delivery of Sofosbuvir to the Liver: A Promising Treatment for Hepatitis C, Molecular Pharmaceutics Article ASAP, DOI: 10.1021/acs.molpharmaceut.4c01529
Read also our introduction article on Capsules here:
