Preparation and characterization of the Adriamycin‑loaded amphiphilic chitosan nanoparticles and their application in the treatment of liver cancer

Abstract

In the present study, two nanoparticles including lactose myristoyl carboxymethyl chitosan (LMCC) and algal polysaccharide myristoyl carboxymethyl chitosan (AMCC), were obtained for hepatic-targeted Adriamycin (ADM) drug delivery systems. ADM was successfully loaded into the LMCC or AMCC nanoparticle by dialysis. The release function and liver targeting of the nanoparticles was explored, and it was revealed that ADM release from the nanoparticles was greatest at acidic pH 5.5. ADM-conjugated nanoparticles were readily taken up by HU7 human hepatocellular carcinoma cells, relative to HT22 mouse hippocampal neuron cells in vitro. In vivo, ADM-loaded nanoparticles had significant antitumor efficacy with a 62.7% inhibition rate, followed by ADM and ADM-AMCC (51.2 and 42.5%, respectively). The tissue distribution study confirmed that ADM-LMCC had an improved liver delivery efficacy, by comparison with ADM. Furthermore, a series of safety studies, including hemolysis, acute toxicity and organ toxicity, revealed that the ADM-loaded LMCC and AMCC nanoparticles had advantages over the commercially available injectable preparation of Adriamycin hydrochloride, in terms of low toxicity levels and increased tolerated dose. These results indicated that LMCC is a promising carrier for injectable ADM nanoparticle and ADM-conjugated nanoparticles may improve the efficacy of ADM by hepatic targeting.

Chitosan Nanoparticles for Therapy and Theranostics of Hepatocellular Carcinoma (HCC) and Liver-Targeting

“…An amphiphilic chitosan was prepared by a derivatization process, obtaining myristoylcarboxymethyl-chitosan; this polymer was then combined with lactose that has been demonstrated to have a ligand targeting function [102]. Adriamycin-loaded lactose myristoyl-carboxymethyl-chitosan nanoparticles were then prepared [103] to obtain drug targeting for the therapy of HCC. In vitro experiments, on HU7 human hepatocellular carcinoma cells, and in vivo studies, using a subcutaneous H22 xenograft tumor model in mouse were performed.…”

Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity

“…These results are indicative of the relevant lipase role in Viol release. However, the Viol release was faster than in pH = 7.4 buffer, with around 65% of the drug released in the first 2 h, which can be expected since Chi solubility is greatly enhanced at lower pH ( Kou et al, 2017 ).…”

Lung carcinoma therapy using epidermal growth factor receptor‑targeted lipid polymeric nanoparticles co‑loaded with cisplatin and doxorubicin

“…However, other ratios showed no synergistic effect than the single drug-loaded LPNs. The reason might be attributed to differences in the controlled release manner and also different dosages of drugs have different effects on cancer cells (24,43). The drug-loaded particles were mainly taken up by cells via the endocytosis pathway and then exerted antitumor activity after the drug molecules were released from the NPs, thus different dosages and ratios of drugs may have different effects, some synergistic and others antagonistic.…”

“…Animal model. Male C57BL/6 mice (6 weeks of age, 20-25 g) were purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China) and raised under conventional conditions with a 12-h light/dark cycle, constant temperature (25˚C) and humidity (60%), and free access to standard food and water (24). To produce the animal model, the mice were injected with A549 cells (1x10 6 cells in 100 µl PBS/mouse) into the right flank, followed by assays for tumor growth.…”