RESUMO
INTRODUCTION: Lyotropic liquid crystals (LLCs) are organized mesophases with intermediate properties between liquids and solids. The LLC and its liquid crystalline nanoparticles (LCNPs) have attracted great interest from the scientific community in recent years as potential drug delivery systems due to the high internal ordering and symmetry with a wide interfacial area. AREAS COVERED: This article aims to gather information and to provide a description of the highly organized structures of LLCs. Updates on production methods and new insights for LCNPs optimization and physico-chemical and morphological caracterization techniques were discussed. We also discussed why these systems proved to be a platform for the design of nanocarrier drug delivery, with an emphasis on topical and transdermal applications. EXPERT OPINION: Drug delivery platforms are of particular importance to improve the biopharmaceutical aspects of therapies topically. Although several systems can be used, LLC or LCNPs appear to be favored due to their similarity to the lipid structure of the skin. The highly ordered structure and the possibility of chemical modifications make it possible to obtain better clinical responses. The results of several studies support the innovations in this field and predict that these systems can innovate the market of technologies for the treatment of cutaneous diseases and cosmetology.
Assuntos
Sistemas de Liberação de Medicamentos , Cristais Líquidos/química , Nanopartículas , Administração Cutânea , Animais , Humanos , Preparações Farmacêuticas/administração & dosagem , Pele/metabolismo , Dermatopatias/tratamento farmacológicoRESUMO
Since psoriasis is an immuno-mediated skin disease, long-term therapies are necessary for its treatment. In clinical investigations, tacrolimus (TAC), a macrolide immunosuppressive inhibitor of calcineurin, arises as an alternative for the treatment of psoriasis, acting in some cytokines involved in the pathogenesis of the disease. Here, we aim to study the psoriasis treatment with TAC and siRNA for one of most cytokines expressed in psoriasis, the TNF-α. A multifunctional nanostructure lipid carrier (NLC) was developed to co-delivery TAC and siRNA. Results showed that the particle size and zeta potential were around 230 nm and + 10 mV, respectively. The release study demonstrated a controlled release of TAC, and the permeation and retention profile in the skin tissue show to be promising for topical application. The cell viability and uptake in murine fibroblast presented low toxicity associated to uptake of NLC in 4 h, and finally, the in vivo animal model demonstrates the efficiency of the NLC multifunctional, exhibiting a reduction of the cytokine TNF-α expression about 7-fold and presenting a synergic effect between the TAC and TNF-α siRNA. The developed system was successfully to treat in vivo psoriatic animal model induced by imiquimod and the synergic combination was reported here for the first time. Graphical abstract.
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Imiquimode/efeitos adversos , Psoríase/tratamento farmacológico , RNA Interferente Pequeno/administração & dosagem , Tacrolimo/administração & dosagem , Fator de Necrose Tumoral alfa/genética , Administração Cutânea , Animais , Preparações de Ação Retardada , Modelos Animais de Doenças , Regulação para Baixo , Sinergismo Farmacológico , Feminino , Lipossomos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Nanopartículas , Tamanho da Partícula , Psoríase/induzido quimicamente , Psoríase/genética , RNA Interferente Pequeno/farmacologia , Tacrolimo/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidoresRESUMO
The majority of FDA-approved biology-derived products are recombinant glycoproteins. These proteins have been used for the treatment of several diseases, with numerous products currently approved for clinical use. The choice of the expression system is a key step toward a successful functional protein production, since glycosylation influences yield, pharmacokinetics, biological activity, and immunogenicity. This chapter covers the general aspects of therapeutic recombinant glycoproteins and the platforms that are being employed for their production.
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Glicoproteínas/farmacologia , Glicoproteínas/uso terapêutico , Proteínas Recombinantes/farmacologia , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Glicosilação/efeitos dos fármacos , HumanosRESUMO
Serum-free suspension cultures are preferably required for recombinant protein production due to its readiness in upstream/downstream processing and scale-up, therefore increasing process productivity and competitiveness. This type of culture replaces traditional cell culturing as the presence of animal-derived components may introduce lot-a-lot variability and adventitious pathogens to the process. However, adapting cells to serum-free conditions is challenging, time-consuming, and cell line and medium dependent. In this chapter, we present different approaches that can be used to adapt mammalian cell lines from an anchorage-dependent serum supplemented culture to a suspension serum-free culture.
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Adaptação Fisiológica/fisiologia , Meios de Cultura Livres de Soro/metabolismo , Glicoproteínas/metabolismo , Proteínas Recombinantes/metabolismo , Animais , Técnicas de Cultura de Células/métodos , Linhagem Celular , Mamíferos , Suspensões/metabolismoRESUMO
ABSTRACT Lentiviral vector-mediated gene transfer offers several advantages over other gene delivery vectors when considering gene and cell therapy applications. However, using these therapies in clinical applications involves large-scale vector production in an efficient and cost-effective manner. Here we describe a high yield production of a lentivirus encoding recombinant factor VIII in a scalable and GMP-compliant culture system, based on serum free suspension cultures and transient transfection with an inexpensive reagent, polyethylenimine (PEI), reaching a total viral yield of 2.48x108 particles.