Development and characterization of PLGA nanocapsules of grandisin isolated from Virola surinamensis: in vitro release and cytotoxicity studies

Abstract

The most studied phyto constituent isolated from Virola surinamensis (Rol. ex Rottb.) Warb., Myristicaceae, is the tetrahydrofuran neolignan grandisin, which exhibits a series of biological activities, including trypanocidal, larvicidal and antitumoral. Due to its extremely low solubility, additional studies, including in vivo investigations are challenged by the difficulties in the development of an effective drug delivery system for grandisin. The encapsulation in polymeric nanoparticles is a very attractive alternative for overcoming some of these limitations. In this work, PLGA nanocapsules loaded with grandisin were developed in an attempt to optimize the efficacy of grandisin as an antitumoral drug, with high drug loading and efficiency, prolonged drug release and increased physical-chemical stability. Mean diameter of the nanocapsules was lower than 200 nm, with very low polydispersity. Encapsulation efficiency was above 90%. A sustained in vitro drug release was achieved for up to twenty days and cytotoxicity was markedly increased (IC50 for grandisin-NC and grandisin were 0.005 µM and 0.078 µM, respectively), indicating that polymeric nanocapsules are a potential drug delivery system for grandisin allowing the preparation of formulations viable for further in vivo studies

Characterization and in vitro antitumor activity of polymeric nanoparticles loaded with Uncaria tomentosa extract

“…Indeed, the burst release was higher for Np UT-PLGA, which presented a lower EE and, therefore, had a higher concentration of nonentrapped alkaloids dispersed in the aqueous phase. The initial burst release, as the observed for Np UT-PCL and Np UT-PLGA, is a frequent event in drug release studies from nanoparticles loaded with natural compounds and some works have reported an initial burst release around 30% (Stecanella et al 2013, Yin et al 2012 or even 50% in the first 12 hours of the study (Yusuf et al 2012, Li et al 2010, Shao et al 2009. Np UT-PCL presented a much slower delivery rate, releasing about 60% of the alkaloids in 20 days, while Np UT-PLGA released the same amount in five days (Figure 4).…”

Colon Drug Delivery Systems for the Treatment of Inflammatory Bowel Disease.

“…Many biodegradable and biocompatible polymers are used i.e. poly (D,L-Lactide-co-glycolic acid) (PLGA) [171,172], poly (lactic acid) (PLA) [173], poly-epsilon-caprolactone (PCL) [174], poly (cyanoacrylate) (PCA) [175,176] and methacrylate copolymers as Eudragit® [177][178][179][180][181][182]. Nanoprecipitation method is the most common and widely used method [183][184][185][186].…”

Improving drug biological effects by encapsulation into polymeric nanocapsules

“…Although in vitro methods present limitations, these studies are important tools to predict the efficacy of substances prior to performing in vivo experiments. In vitro assays have been applied to evaluate the effects of nanoencapsulation on the antiproliferative, antioxidant, and anti‐inflammatory activities of drugs, as well as on photoactivity, phototoxicity and photoprotection …”

“…The most common in vitro assay related to nanocapsule efficacy is the antiproliferative effect using cancer cell lines, including glioma cells, breast cancer cells, prostate cancer cells, embryonal renal cancer cells, leukemia cells and colon adenocarcinoma cells . Non‐cancer cells have also been used . The cytotoxicity effect of the substance is frequently measured by tetrazolium reduction assays (MTT and MTS tests), by neutral red assay, by nitroblue tetrazolium reduction assay, by sulforhodamine B assay, by propidium iodide assay or by cell counting …”