Anticancer activity of polymeric nanoparticles containing linoleic acid-SN38 (LA-SN38) conjugate in a murine model of colorectal cancer.

Biodegradable polymeric nanoparticles (NPs) have been used frequently as nanocarriers for anticancer drugs. Linoleic acid conjugated SN38 (LA-SN38)-loaded NPs (EBNPs) were developed using biodegradable poly (ethylene oxide)-poly (butylene oxide) (PEO-PBO) diblock copolymer by titration hydration method without using a toxic organic solvent. The EBNPs had high drug loading efficiency and entrapment efficiency for LA-SN38, at 7.53% and 93.55%, respectively. The polydispersity index (PDI) and average diameter were 0.173 ±â€¯0.019 and 226.1 ±â€¯1.2 nm, respectively. The transmission electron microscope (TEM) image presented that the NPs were homogeneous in size and had spherical structures. In vitro study showed the release behavior of EBNPs was slow and sustained. Furthermore, cytotoxicity and apoptosis assay proved that EBNPs were more effective in growth inhibition of human colon cancer cells. Cell uptake experiments further demonstrated that EBNPs could avoid the phagocytosis by macrophages and promote the uptake by cancer cells. In vivo, EBNPs had prolonged blood circulation time and tumor selectivity in biodistribution. The tumor inhibitory rate of EBNPs was higher compared to SNPs group and CPT-11group (P < 0.01), and the drug did not show significant systemic toxicity at the tested dose. These results indicated that EBNPs are a promising candidate for delivery of LA-SN38 to treat colorectal cancer.

Facile Assembly of Cost-Effective and Locally Applicable or Injectable Nanohemostats for Hemorrhage Control.

Currently, there is still unmet demand for effective and safe hemostats to control abnormal bleeding in different conditions. With the aim to develop affordable, safe, effective, easily stored, and low-cost hemostats, we developed a series of positively charged nanoparticles by a facile one-pot assembly approach. In this strategy, nanoparticles were formed by cholic-acid-mediated self-assembly of polyethylenimine (PEI). Regardless of different structures of cholic acids and PEIs, well-defined nanoparticles could be successfully formed. The assembly process was dominated by multiple interactions between cholic acid and PEI, including electrostatic, hydrogen bonding, and hydrophobic forces. In vitro studies showed that assembled nanoparticles effectively induced aggregation and activation of platelets. Local application of aqueous solution containing nanoparticles assembled by different cholic acids and PEIs significantly reduced bleeding times in different rodent models including tail transection in mice as well as liver bleeding and femoral artery bleeding in rats or rabbits. Moreover, intravenous (i.v.) injection of this type of positively charged nanoparticles notably prevented bleeding in the femoral artery in rats by targeting the injured site via opsonization of nanoparticles with fibrinogen. By contrast, a control negatively charged nanoparticle showed no hemostatic activity after i.v. delivery. Also, preliminary evaluations in rats revealed a good safety profile after i.v. administration of assembled nanoparticles at a dose 4-fold higher than that used for hemostasis. These results demonstrated that cholic acid/PEI-assembled positive nanoparticles may function as cost-effective and locally applicable or injectable nanohemostats for hemorrhage control in the civilian setting and on the battlefield.

Development of oral dispersible tablets containing prednisolone nanoparticles for the management of pediatric asthma.

The purpose of the present study was to develop oral dispersible tablets containing prednisolone (PDS)-loaded chitosan nanoparticles using microcrystalline cellulose (MCC 101), lactose, and croscarmellose sodium (CCS). The PDS-loaded chitosan nanoparticles were formulated by ionotropic external gelation technique in order to enhance the solubility of PDS in salivary pH. Prepared nanoparticles were used for the development of oral fast disintegrating tablets by direct compression method. The prepared tablets were evaluated for disintegration time (DT), in vitro drug release (DR), thickness, weight variation, drug content uniformity, friability, and hardness. The effect of concentrations of the dependent variables (MCC, lactose, CCS) on DT and in vitro DR was studied. Fast disintegrating tablets of PDS can be prepared by using MCC, CCS, and lactose with enhanced solubility of PDS. The minimum DT was found to be 15 seconds, and the maximum DR within 30 minutes was 98.50%. All independent variables selected for the study were statistically significant. Oral fast disintegrating tablets containing PDS nanoparticles could be the better choice for the pediatric patients that would result in better patient compliance. From this study, it can be concluded that fast disintegrating tablets could be a potential drug delivery technology for the management of asthma in pediatrics.