Substance active (médicament)

Résumé

Une substance active, principe actif ou ingrédient actif désigne une substance chimique qui entre dans la composition d'un médicament parce que ce composé bioactif a un effet thérapeutique ou préventif. Par métonymie, le terme médicament peut être aussi utilisé pour désigner la substance active. Cependant, une substance active, en soi, peut être bénéfique ou nocive. La pharmacologie a pour objectif de sélectionner les substances actives bénéfiques et de déterminer les doses appropriées. Le principe actif est généralement en très faible proportion par rapport aux excipients. Ce peut être une substance pure dont on connaît la structure chimique et qui est obtenue par des méthodes de synthèse chimique ; dans ce cas, on la désigne aussi par le terme « molécule » quand on veut mettre en avant sa structure. Cela peut aussi être un mélange de plusieurs substances chimiquement proches (par exemple des isomères) ou encore une substance définie par son mode d'obtention : sen

Source officielle

https://fr.wikipedia.org/wiki/Substance_active_(m%C3%A9dicament)

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Encapsulation techniques open up new possibilities to control the kinetics and location of the release of active ingredients. Despite the progresses achieved to obtain a better control over the dimensions and composition of the capsules, the encapsulation of volatile substances is still challenging, even though it is of high relevance especially for the cosmetic industries. One way of encapsulating volatile substances is by kinetically arresting these molecules in a matrix which has a low permeability. A group of materials that likely is well-suited to generate such matrices is composed of small molecules capable of forming crystals.In this thesis, we will investigate the influence of the processing of composites containing small biocompatible organic molecules that serve as matrices with volatile active ingredients on the structure and permeability of the resulting particles. In particular, we will investigate the possibility to use organic salt crystals as matrix materials. Particles of well-defined sizes and compositions will be produced in double emulsions where the influence of the formation kinetics and confinements on the structure and permeability of the particles will be investigated. In addition, we will produce amorphous particles by kinetically suppressing the crystallization reaction using a microfluidic spray-drier. This will be achieved by co-spray-drying the active ingredient with the matrix material. We will investigate the effect of the drying speed and reactant composition on the structure and composition of the resulting particles and relate that to the release kinetics of the active ingredient. In addition, we will crystallize the amorphous composite particles and investigate the influence of the structure on the distribution of the actives within the matrix and its permeability. This project is done in collaboration with Firmenich who has all the infrastructure to quantify the release kinetics of volatile active ingredients.

EPFL2022

Chargement

Repurposed drug combination via high-throughput screening and dual drug delivery system development for the treatment of retinoblastoma

Po-Jen Tseng

The goal of retinoblastoma (RB) treatment is to save the child's life, eyes and functional vision, with that order of priority. The management of RB is complex and involves strategically chosen methods of surgical enucleation, external beam radiotherapy, intravenous chemoreduction and focal therapy. Local administration routes of chemotherapy, intra-arterial (IAC) and intravitreal (IVC), have emerged as promising methods to salvage the eyes and vision. New improvements in the chemotherapy of RB are geared towards reducing side effects of the drugs employed. Emerging strategies includes alternative chemotherapeutic agents, drug combinations, and novel drug delivery systems. Most successful examples of drug repurposing so far have been serendipitous. The systematic approach here was identified candidate drugs by strategic high-throughput screening methods. In this thesis, hit drugs were screened from a drug library of primarily FDA-approved drugs, and the synergistic effect of selected drug combinations was investigated. The hit drug gemcitabine, known to be an effective clinical treatment for non-small cell lung cancers, in combination with carboplatin, was discovered to have the highest cytotoxicity of the hits identified, and appeared as a potential alternative therapeutic agent for RB treatment.Polymeric nanoparticles (NPs) as an improved drug delivery system were investigated with gemcitabine. The nanoprecipitation synthesis of a poly(lactic-co-glycolic acid), as known as PLGA, nanoparticle was developed for drug encapsulation. The characterization of PLGA NPs within various active pharmaceutical ingredients were studied using dynamic light scattering and scanning electron microscopy, revealing that spherical NPs ranging in size from 150 to 200 nm could be successfully prepared. The tumor cells proliferation inhibition was observed after treatment with this novel nanoformulation. Furthermore, the possibility of a dual drug delivery system was explored. Gemcitabine and carboplatin were encapsulated together in PLGA NPs and found to show a synergistic effect after dual drug release. Additionally, gemcitabine combined with the light-activated agent indocyanine green was prepared, and laser-induced photothermal therapy (PTT) was explored.

EPFL2022

Chargement

Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes

Léo Bühler, Sandrine Gerber, Yi Wang, Qixing Zhang

Islet transplantation is a promising approach for the treatment of type 1 diabetes (T1D). Currently, clinical islet transplantation is limited by allo - and autoimmunity that may cause partial or complete loss of islet function within a short period of time, and long-term immunosuppression is required to prevent rejection. Encapsulation into semipermeable biomaterials provides a strategy that allows nutrients, oxygen and secreted hormones to diffuse through the membrane while blocking immune cells and the like out of the capsule, allowing long-term graft survival and avoiding long-term use of immunosuppression. In recent years, a variety of engineering strategies have been developed to improve the composition and properties of encapsulation materials and to explore the clinical practicality of islet cell transplantation from different sources. In particular, the encapsulation of porcine islet and the co-encapsulation of islet cells with other by-standing cells or active ingredients for promoting long-term functionality, attracted significant research efforts. Hydrogels have been widely used for cell encapsulation as well as other therapeutic applications including tissue engineering, cell carriers or drug delivery. Here, we review the current status of various hydrogel biomaterials, natural and synthetic, with particular focus on islet transplantation applications. Natural hydrophilic polymers include polysaccharides (starch, cellulose, alginic acid, hyaluronic acid, chitosan) and peptides (collagen, poly-L-lysine, poly-L-glutamic acid). Synthetic hydrophilic polymers include alcohol, acrylic acid and their derivatives [poly (acrylic acid), poly (methacrylic acid), poly(acrylamide)]. By understanding the advantages and disadvantages of materials from different sources and types, appropriate materials and encapsuling methods can be designed and selected as needed to improve the efficacy and duration of islet. Islet capsule transplantation is emerging as a promising future treatment for T1D.

2022

Chargement

Islet Encapsulation: New Developments for the Treatment of Type 1 Diabetes

Léo Bühler, Sandrine Gerber, Yi Wang, Qixing Zhang

2022

Repurposed drug combination via high-throughput screening and dual drug delivery system development for the treatment of retinoblastoma

Po-Jen Tseng

EPFL2022