Modification of ChPL (chitosan protein–lipid) nanoparticles for in vitro release of rifampicin (RIF)

Abstract

During recent years, the implication of nanoparticles (NPs) as drug delivery systems has gained much scientific attention. As drugs do not deliver themselves, a nanoparticle can act by optimizing drug delivery in the right place, at the right time and at the right dosage. In previous years, this research successfully developed and evaluated the ChPL-NPs nanoparticles (chitosan protein–lipid) [US patent pending 20140370500]. In the present investigation, rifampicin (RIF) ChPL-NPs nanoparticles were designed and developed. Consequently, the in vitro release of RIF ChPL-NPs nanoparticles was investigated. Material and methodsBriefly, chitosan powder (90 KD and 90% degree of deacetylation) was dissolved (1% acetic-acid) and mixed with gelatin (3%). Then, the lipid and rifampin in ether was precipitated by rotary vacuum evaporator. Under high speed homogenizer (12,000rpm), both solutions (chitosan–gelatin & rifampin–lipid) were mixed [US patent pending 20140370500]. The obtained RIF ChPL-NPs were put into a dialysis bag with cut-off 14 KD in phosphate buffer solution (pH=7.4). The release of RIF was obtained by reverse phase HPLC using C18 (250×4.6mm, 5μm) column. The mobile phase consisted of 50:50 v/v acetonitrile and 10mm potassium dihydrogen phosphate (pH=3.2) and flow rate 1ml/min. The column temp was maintained at 25°C with UV detection at 335nm. Results and conclusionsThe average size of RIF ChPL-NPs was about 50–250nm. The release of RIF from the dialysis bag started after 30min which was 2400ng/ml; after 16h the release of RIF was 15,000ng/ml; and at 40h the concentration reached to 19,600ng/ml. Therefore, these results showed a slow release of RIF from ChPL-NPs. Basically, the intensity of the surface charges in nanoparticle is important as it determines their interaction with bioactive compound. In RIF ChPL-NPs, lipid had negative charges, whereas chitosan and gelatin had positive charges. The electrostatic interaction between oppositely charged ions would ultimately cause an effective system drug delivery. RIF ChPL-NPs is not only suitable for intravenous administration, but it can be used as an inhalation aerosol, because this nanoparticle has a capacity to adhere to mucosal surfaces and transiently open the tight junction.