Poly-ε-caprolactone microspheres containing interferon alpha as alternative formulations for the treatment of chronic hepatitis C

Abstract

Interferon-alpha (IFN-alpha) is one of the main drugs used in the treatment of hepatitis C. Use of IFNalpha has some limitations that result in poor treatment efficacy and low patient compliance. Therefore, the aim of this study was to develop poly-ε-caprolactone (PCL) microspheres containing IFN-alpha as an alternative for the treatment of chronic hepatitis C. Microspheres were prepared using the multiple emulsion followed by solvent evaporation technique. Particle size, surface morphology, drug content and encapsulation efficiency of the microspheres produced were evaluated. The stability of the formulation was assessed after 90 days at -20ºC. An in vitro release study was performed in PBS. In vitro cytotoxicity of the formulation was studied using hepatic cell line. The freeze-dried microspheres had mean particle size, IFN-alpha content, and encapsulation efficiency of 38.52 ± 4.64 mm, 15.52 ± 3.28% and 83.93 ± 5.76%, respectively. There were no significant changes during storage and the structural integrity of the protein was not compromised by the preparation technique. A total of 82% of the IFN-alpha was released after 28 days and the developed microspheres did not present cytotoxicity to the hepatic cell line. In vivo studies are currently underway to evaluate the biological activity of IFN-alpha encapsulated into microspheres.Uniterms: Interferon alfa. Hepatitis C/treatment. Poly-ε-caprolactone/microspheres/development. O interferon alfa (IFN-alfa) é um dos principais fármacos utilizados no tratamento de hepatite C, mas o seu uso apresenta limitações que resultam em baixa eficácia do tratamento e não adesão do paciente. Diante disso, este estudo objetiva o desenvolvimento de microesferas de poli-ε-caprolactona (PCL) contendo IFN-alfa como alternativa ao tratamento de hepatite C crônica. As microesferas foram preparadas pelo método de emulsão múltipla seguido de evaporação do solvente e caracterizadas quanto ao diâmetro médio das partículas, morfologia da superfície, taxa e eficiência de encapsulamento. A estabilidade da formulação foi acompanhada durante 90 dias a -20 ºC. O estudo de liberação in vitro foi realizado em PBS. A citotoxicidade da formulação foi avaliada utilizando linhagem de células hepáticas. As microesferas liofilizadas apresentaram diâmetro médio, taxa de encapsulamento e eficiência de encapsulamento de 38,52 ± 4,64 mm, 15,52 ± 3,28% e 83,93 ± 5,76%, respectivamente. Não foram observadas alterações significativas durante o armazenamento e a integridade estrutural da proteína foi mantida após o preparo. Oitenta e dois por cento de IFN-alfa foram liberados em 28 dias e a formulação desenvolvida não apresentou toxicidade para as células testadas. Estudos in vivo estão em andamento para avaliar a atividade biológica do IFN-alfa encapsulado nas microesferas.Unitermos: Interferon alfa. Hepatite C/tratamento. Poli-ε-caprolactona/microesferas/desenvolvimento.

In Vitro IFN-α Release From IFN-α- and Pegylated IFN-α-loaded poly(lactic-co-glycolic acid) and Pegylated poly(lactic-co-glycolic acid) Nanoparticles

“…In recent studies carried out with micro-or nanoparticles designed for parenteral sustained delivery of IFN- [5,7,9], the in-vitro release experiments were performed exclusively in phosphate buffered saline (PBS). Because blood proteins, especially albumin, have an important protective role towards the interferon molecule, we investigated the in-vitro release profiles both in human blood plasma and PBS.…”

“…Giri et al [6] synthesised IFN- loaded cationic PLGA nanoparticles with delipidated HBsAg adsorbed on the surface of nanoparticles. Besides PLGA, a number of other micro/nanocarriers such as poly-ε-caprolactone microspheres [7], lipid-based nanostructures [8] and lipid coated aquasomes [9] have also been investigated as human IFN- delivery systems. However, it is well-known that serum proteins are easily adsorbed onto hydrophobic polymeric nanoparticles such as PLGA [10], and the so-called opsonisation results in the fast clearance of these nanoparticles by the macrophages of RES from the blood circulation.…”