Polymeric Nano-Micelles as Novel Cargo-Carriers for LY2157299 Liver Cancer Cells Delivery

Abstract

LY2157299 (LY), which is very small molecule bringing high cancer diffusion, is a pathway antagonist against TGFβ. LY dosage can be diluted by blood plasma, can be captured by immune system or it might be dissolved during digestion in gastrointestinal tract. The aim of our study is to optimize a “nano-elastic” carrier to avoid acidic pH of gastrointestinal tract, colon alkaline pH, and anti-immune recognition. Polygalacturonic acid (PgA) is not degradable in the gastrointestinal tract due to its insolubility at acidic pH. To avoid PgA solubility in the colon, we have designed its conjugation with Polyacrylic acid (PAA). PgA-PAA conjugation has enhanced their potential use for oral and injected dosage. Following these pre-requisites, novel polymeric nano-micelles derived from PgA-PAA conjugation and loading LY2157299 are developed and characterized. Efficacy, uptake and targeting against a hepatocellular carcinoma cell line (HLF) have also been demonstrated.

Mucoadhesive Hydrogel Nanoparticles as Smart Biomedical Drug Delivery System

“…Moreover, chitosan possesses NH2 groups that can react with mucin forming electrostatic interpenetration [48]. (Figure 3) [49]. This result is consistent with its hydrophobic properties [50].…”

“…Polygalacturonic acid (PgA) is a natural polymer with a heterogeneous structure bonded via α (1,4) glycosidic linkage. Hanafy and his colleagues have demonstrated that PgA has limited dissolution in distilled water, Phosphate buffer saline (pH7.3), and acidic distilled water (pH3), resulting in white turbidity (Figure 3) [49]. This result is consistent with its hydrophobic properties [50].…”

“…Poly(acrylic acid) (PAA) is a hydrophilic polymer [56] that adopts a random coil conformation in solution. In their recent work, Hanafy and his colleagues have further demonstrated that these coils have swelling properties under certain ionic strengths and salt concentrations, leading to extended chain conformations in alkaline solutions (Figure 4) [49,[57][58][59]. This is due to the COOH side chain which is pH responsive, i.e., protonated (COOH) at pH ≤5while de-protonated (COO-) at pH >5 [60].…”

<p>Nanocarrier-Based Therapeutics and Theranostics Drug Delivery Systems for Next Generation of Liver Cancer Nanodrug Modalities</p>

“…Huang et al, (2010) synthesized glycyrrhetinic acid (GA)modified PM loaded with doxorubicin which has great potential in liver targeting therapy. 17 Hanafy et al (2018) synthesized a novel PM (polyacrylic\poly-galacturonic acid hybrid) loaded with drug galunisertib (LY2157299) which acts as an inhibitor of TGFβ to treat hepatocellular carcinoma. 19 Yang et al, (2019) synthesized a nanocarrier of polyethylene glycol-derivatized glycyrrhizic acid (GA)based PM loaded with doxorubicin which is delivered in HepG2 cell line.…”

“…17 Hanafy et al (2018) synthesized a novel PM (polyacrylic\poly-galacturonic acid hybrid) loaded with drug galunisertib (LY2157299) which acts as an inhibitor of TGFβ to treat hepatocellular carcinoma. 19 Yang et al, (2019) synthesized a nanocarrier of polyethylene glycol-derivatized glycyrrhizic acid (GA)based PM loaded with doxorubicin which is delivered in HepG2 cell line. 9 This PM demonstrated excellent therapeutic efficacy in vivo compared with free doxorubicin.…”