In vitro characterisation of PLGA nanoparticles encapsulating rifampicin and isoniazid - Towards IVIVC

Abstract

It has been postulated that antituberculosis drugs encapsulated in polymeric nanoparticles are able to control the release of these drugs in vivo. These biodegradable polymers facilitate sustained/controlled release by means of degradation of the polymer or by diffusion through the polymer matrix. For oral drug delivery, one of the most important parameters to be elucidated is the absorption of not only the drugs, but also of the nanoparticles. These nanoparticles are postulated to be absorbed in tact and be transported through the lymphatic system. Once in the systemic circulation, the biodistribution of the particles is highly dependent on its response to the biological environment, mainly binding to plasma proteins. Nanoparticle characteristics such as surface hydrophobicity, size and polymer composition determine the extent of adsorption of blood components, mainly proteins such as albumin and glycoproteins1. For drugs with a high degree of protein binding, protein adsorption effects on volume of distribution are observed2. Another class of proteins that plays an important role in protein binding are opsonins. Binding of these proteins promotes the activation of the complement system and facilitates phagocytotic uptake by macrophages3. To minimise opsonisation, the surfaces of nanoparticles can be modified with biodegradable copolymers with hydrophilic segments such as polyethylene glycol (PEG), including poloxamines and polysorbate 80 which will eventually prolong the duration of systemic circulation of the nanoparticles4. The objective of the current study was to determine the effect that PLGA (coated/ uncoated with PEG/Pluronic F127) nanoencapsulation of rifampicin (RIF) and isoniazid (INH) has on plasma protein binding of these drugs in vitro. Furthermore, the biodistribution of Rhodamine 6G labelled PEG-coated and Pluronic F127- coated nanoparticles was evaluated.