Alphastatin-Loaded Chitosan Nanoparticle Preparation and Its Antiangiogenic Effect on Lung Carcinoma

Abstract

Alphastatin is a 24-amino acid peptide and can suppress tumor angiogenesis by inhibiting both the migration and tubule formation of vascular endothelial cells. However, the anticancer effect of Alphastatin is limited due to the short half-life and degradation in the body. In this study, Alphastatin-loaded chitosan nanoparticles (AsCs NPs) were prepared with an initial concentration of 2 mg/ml for chitosan and 1 mg/ml for Alphastatin. AsCs NPs presented the encapsulation efficiency of 32.4%, the mean particle size of 387.4 nm, the polydispersity index of 0.223, and the zeta potential of +28.1 mV. AsCs NPs have a sustained release for 6 days and were stable in serum for at least 24 hours. And the NPs could preserve the integrity of encapsulated Alphastatin and released Alphastatin for 24 hours. In a subcutaneous LA975 lung carcinoma xenograft T739 mouse model, AsCs NPs significantly inhibited the tumor growth, tumor volume, and microvessel density (MVD), and the antitumor effect was even stronger than that of Alphastatin. In addition, the VEGF-induced tube formation of HUVEC could be inhibited by AsCs NPs in vitro and the serum containing AsCs NPs, and the protein level of SphK1 in HUVEC was also decreased by AsCs NPs, suggesting an inhibitory effect of AsCs NPs on the SphK1-S1P signaling pathway. Furthermore, hemolysis assay showed a safety on blood compatibility of AsCs NPs. Our study indicated that AsCs NPs inhibited the SphK1-S1P signaling pathway and enhanced the antiangiogenic effect of Alphastatin both in vitro and in vivo.

Microencapsulation of Fluticasone Propionate and Salmeterol Xinafoate in Modified Chitosan Microparticles for Release Optimization

“…The prepared blank particles are in the nanometric scale and thus are too small for delivery by inhalation; however, upon loading with FLU and SX, the obtained drug-loaded particles are bigger and thus more appropriate for inhalation administration. This observation is in agreement with the literature [ 60 , 61 ]. More specifically, as presented in Table 2 , the DLS results indicate that the size of drug-loaded microparticles ranges approximately between 1.2 and 2.2 μm for all CS derivatives except CS-g-PAA-TPP.…”

“…Initially, each sponge was carefully weighed (W0) and immersed in buffer for several hours. At predetermined time intervals (i.e., 10,15,20,30,40,60,90, 120 and 180 min), the swollen samples were removed from the buffer, wiped with a filter paper to remove the excess surficial water, and weighed once more with the purpose of determining the swelling weight (W n ). The percent weight alteration of the polymeric matrix throughout the swelling experiment (i.e., cumulative weight changes due to matrix swelling and erosion, S (ti) %) was measured through the following formula:…”

Polymers and Polymer Nanocomposites for Cancer Therapy

“…The prepared AS/CS nanoparticles had a sustained release of 6 days and were stable in serum for at least 24 h. In a subcutaneous LA975 lung carcinoma xenograf T739 mouse model, the nanoparticles significantly inhibited tumor growth, tumor volume, and microvessel density, and the antitumor effect was even stronger than that of AS. The study indicated that AS/CS nanoparticles inhibited the SphK1 signaling pathway and enhanced the antiangiogenic effect of the drug both in vitro and in vivo [48].…”

ULK1 Mediated Autophagy-Promoting Effects of Rutin-Loaded Chitosan Nanoparticles Contribute to the Activation of NF-κB Signaling Besides Inhibiting EMT in Hep3B Hepatoma Cells

“… 264 Since the desired percentage of hemolysis is less than 5%, the rCNPs are safe to use (with non-hemolytic profile) and can be administered intravenously owing to their compatibility with blood. 138 …”