Folate Functionalized and Evodiamine-Loaded Pluronic Nanomicelles for Augmented Cervical Cancer Cell Killing.

Evodiamine (Evo) is a natural, biologically active plant alkaloid with wide range of pharmacological activities. In the present study Evo-loaded folate-conjugated Pluronic F108 nano-micelles (ENM) is synthesized to enhance the therapeutic efficacy of Evo against cervical cancer. ENM are synthesized, physicochemically characterized and in vitro anticancer activity is performed. The study demonstrates that ENM have nanoscale size (50.33 ± 3.09 nm), monodispersity of 0.122 ± 0.072, with high drug encapsulation efficiency (71.30 ± 3.76%) and controlled drug release at the tumor microenvironment. ENM showed dose-dependent and time-dependent cytotoxicity against HeLa human cervical cancer cells. The results of in vitro anticancer studies demonstrated that ENM have significant anticancer effects and greatly induce apoptosis as compared to pure Evo. The cellular uptake study suggests that increased anticancer activity of ENM is due to the improved intracellular delivery of Evo through overexpressed folate receptors. Overall, the designed ENM can be a potential targeted delivery system for hydrophobic anticancer bioactive compound like Evo.

Biotinylated Mn3O4 nanocuboids for targeted delivery of gemcitabine hydrochloride to breast cancer and MRI applications.

Multifunctional nanocarriers have been found as potential candidate for the targeted drug delivery and imaging applications. Herein, we have developed a biocompatible and pH-responsive manganese oxide nanocuboid system, surface modified with poly (ethylene glycol) bis(amine) and functionalized with biotin (Biotin-PEG-MNCs), for an efficient and targeted delivery of an anticancer drug (gemcitabine, GEM) to the human breast cancer cells. GEM-loaded Biotin-PEG@MNCs showed high drug loading efficiency, controlled release of GEM and excellent storage stability in the physiological buffers and different temperature conditions. GEM-loaded Biotin-PEG@MNCs showed dose- and time-dependent decrease in the viability of human breast cancer cells. Further, it exhibited significantly higher cell growth inhibition than pure GEM which suggested that Biotin-PEG@MNCs has efficiently delivered the GEM into cancerous cells. The role of biotin in the uptake was proved by the competitive binding-based cellular uptake study. A significant decrease in the amount of manganese was observed in biotin pre-treated cancer cells as compared to biotin untreated cancer cells. In MRI studies, Biotin-PEG-MNCs showed both longitudinal and transverse relaxivity about 0.091 and 7.66 mM-1 s-1 at 3.0 T MRI scanner, respectively. Overall, the developed Biotin-PEG-MNCs presents a significant potential in formulation development for cancer treatment via targeted drug delivery and enhanced MRI contrast imaging properties.

Inulin-pluronic-stearic acid based double folded nanomicelles for pH-responsive delivery of resveratrol.

Herein, we introduce a novel amphiphilic bioconjugate (INU-F68-SA), synthesized by functionalization of pluronic F68 with a polysaccharide inulin (INU) and a lipid stearic acid (SA). The synthesis of INU-F68-SA was confirmed by FTIR and 1H-NMR analysis. INU-F68-SA can self-assemble into nanomicelles and therefore, its application in delivering of hydrophobic resveratrol (RSV) was investigated. The RSV-loaded INU-F68-SA nanomicelles (RSNM) had about 172 nm size, spherical shape, 0.237 polydispersity index, and -18 mV zeta potential. More importantly, the RSNM showed high drug entrapment efficiency, controlled drug release and protection of drug during storage. The RSNM significantly enhanced the cytotoxicity of RSV against colorectal cancer cells by inducing apoptosis and changing mitochondrial membrane potential. Further, in-vivo pharmacokinetic experiment indicated an improvement in pharmacokinetics of RSV after administering as RSNM. Thus, the use of self-assembled nanomicelles of amphiphilic INU-F68-SA bioconjugate could be a better alternative to overcome the poor in-vitro and in-vivo performance of RSV.