Preparation and Characterization of Hyaluronic Acid-Polycaprolactone Copolymer Micelles for the Drug Delivery of Radioactive Iodine-131 Labeled Lipiodol

Abstract

Micelles, with the structure of amphiphilic molecules including a hydrophilic head and a hydrophobic tail, are recently developed as nanocarriers for the delivery of drugs with poor solubility. In addition, micelles have shown many advantages, such as enhanced permeation and retention (EPR) effects, prolonged circulation times, and increased endocytosis through surface modification. In this study, we measured the critical micelle concentrations, diameters, stability, and cytotoxicity and the cell uptake of micelles against hepatic cells with two kinds of hydrophilic materials: PEG-PCL and HA-g-PCL. We used 131I as a radioactive tracer to evaluate the stability, drug delivery, and cell uptake activity of the micelles. The results showed that HA-g-PCL micelles exhibited higher drug encapsulation efficiency and stability in aqueous solutions. In addition, the 131I-lipiodol loaded HA-g-PCL micelles had better affinity and higher cytotoxicity compared to HepG2 cells.

Recent Advances in Nanoparticle Development for Drug Delivery: A Comprehensive Review of Polycaprolactone-Based Multi-Arm Architectures

“…PCL-based micelles have multiple advantages, including improved permeation and retention (EPR), increased blood circulation time, and increased endocytosis due to surface modification. For the treatment of hepatocellular carcinoma, Chen and colleagues prepared lipiodol-loaded micelles using polyethylene glycol-polycaprolactone (PEG-PCL) copolymers and amphiphilic hyaluronic acid-polycaprolactone (HA-g-PCL) copolymers [109]. The HA-g-PCL micelles showed high drug encapsulation efficiency (about 71%), stability in aqueous solutions, and high affinity and cytotoxicity towards HepG2 cells, despite their size of 274 nm.…”

Nanomaterials for Drug Delivery and Cancer Therapy

“…However, widespread adoption of liposome-based vaccines remains stunted by their relatively lower physical and chemical stability in aqueous dispersions during long-term storage [118]. Accordingly, numerous methods to improve the stability of liposome formulations during storage have been investigated, including freeze-drying, spray-drying, supercritical fluid technology, and lyophilization [119][120][121].…”

“…Hepatocellular carcinoma (HCC) is the most common malignancy of the liver and the most common cause of morbidity and mortality [121,122]. A few molecular targeting drugs, such as sorafenib (SO), have been approved for advanced HCC, which also show a peripheral survival chance compared to conventional therapeutics.…”

“…Poly(ε-caprolactone) (PCL) is another key polymer widely used in biomedical fields for the preparation of delivery vehicles due to its ability to control the drug release kinetics and not significantly lower the environmental pH upon degradation [136]. SANPs based on HA-PCL conjugate were, indeed, successfully used for the vectorization of chemo- [120] and radio- [121] therapeutics. Moreover, the further insertion of PEG moieties was found to improve the blood circulation time [122], while the derivatization with 2-(Pyridyldithio)ethylamine (PDA) conferred the possibility to perform a post-crosslinking step in the presence of DTT for enhanced GSH responsivity [123].…”

Synthesis of graft copolymers based on hyaluronan and poly(3-hydroxyalkanoates)

“…With the increasing demands of smart nanomicelles or vesicles, it is essential to modify the structure of HA, increase its stability and shelflife i.e. by grafting with synthetic aliphatic polyesters such as poly(lactic acid) (PLA) (Pravata et al, 2007), poly(lactide-co-glycolide) (PLGA) (Son et al, 2014) or poly(caprolactone) (PCL) (Chen et al, 2017). Unfortunately, these conjugates often suffer from several drawbacks due to the use of synthetic blocks, often giving problems due to the presence of unreacted monomers, catalysts, toxic degradation or side-products (Maitz, 2015).…”