Antitumoral activity of camptothecin-loaded nanoparticles in 9L rat glioma model

Abstract

Camptothecin (CPT), a plant alkaloid, is a potent anticancer drug in cell culture studies but it is clinically inactive due to rapid hydrolysis under physiological conditions. The drug exists in two forms depending on the pH value, an active lactone form at pH below 5 and an inactive carboxylate form at basic pH and this is a reversible reaction. In this study, nanoparticulate delivery systems were developed with either amphiphilic cyclodextrins, poly(lactide-co-glycolide) or poly-ɛ-caprolactone in order to maintain the active lactone form and prevent the drug from hydrolysis. All nanoparticles were prepared with nanoprecipitation technique. Mean particle sizes were 130-280nm and surface charges were negative. The encapsulation efficiency was significantly higher for amphiphilic cyclodextrin nanoparticles when compared to polymeric nanoparticles. Nanoparticle formulations based on cyclodextrins showed a controlled release profile extended up to 12 days. 6-O-Capro-β-cyclodextrin (1.44μg/60μL CPT) and concentrated 6-O-Capro-β-cyclodextrin (2.88μg/60μL CPT) nanoparticles significantly modified the growth or lethality of the 9L gliomas, since the median survival time was 26 days for the untreated group and between 27 and 33 days for amphiphilic cyclodextrin nanoparticle groups. These results indicate that, CPT-loaded amphiphilic cyclodextrin nanoparticles may provide a promising carrier system for the effective delivery of CPT in comparison to polymeric analogues.

Evaluation of the cytotoxic effect of camptothecin solid lipid nanoparticles on MCF7 cells

“…Moreover, the critical temperature of carbon dioxide is lower than operation temperature to obtain SLN as well as the operation time. Previous studies (Min et al, 2008;Ç irpanli et al, 2011) have shown that encapsulation of CPT and the preparation of nano-sized drug carriers can be time consuming. Other researchers have used high temperatures (superior to 80 C) with several intermediate steps, in the preparation of CPT:SLN encapsulated (Yang et al, 1999).…”

Poly ε-caprolactone nanoparticles loaded with Uncaria tomentosa extract: preparation, characterization, and optimization using the Box–Behnken design

“…Most publications that have explored the development of NPs loaded with natural compounds have reported the use of isolated substances, with EEs obtained in these formulations remaining only near 50%, 19,[22][23][24] particularly when the natural component loaded was not extremely lipophilic. In contrast, the use of BBD as the chosen DOE method was effective for obtaining optimal formulations for the development of NPs that possess good EEs.…”

“…[13][14][15][16][17] Some studies have even reported PCL as the polymeric matrix of choice. [18][19][20] In these studies, the use of isolated active principles in preparing NP formulations was investigated. However, the use of plant extracts is much less reported.…”

“…Many of these formulation studies have reported entrapment efficiency (EE) values of around 50%. 19,[22][23][24] Special attention is being given to the process of loading natural anti-tumorigenic substances into NP systems; "nanochemoprevention" is thus becoming an increasingly explored concept worldwide. 25 For NP development, it is important that drug delivery systems have predictable release behavior and size distribution and reproducible drug loading.…”

Amphiphilic cyclodextrins as enabling excipients for drug delivery and for decades of scientific collaboration: Tribute to a distinguished scientist, French representative and friend – A historical perspective

“…The release profile was prolonged up to 48 hours with 6-O-CAPRO-β-CD and the anticancer efficacy of camptothecin was significantly increased when encapsulated into amphiphilic CD nanoparticles. These nanoparticles were further evaluated in rat brain glioma model and 6-O-CAPRO-β-CD yielded the highest survival rate among the nanoparticle formulations for camptothecin with drug solution in DMSO used as reference(22,23).…”