Apoptosis Induction and Antimigratory Activity of Andrographolide Analog (3A.1)-Incorporated Self-Assembled Nanoparticles in Cancer Cells

Abstract

Andrographolide analog, namely 19-tert-butyldiphenylsilyl-8,17-epoxy andrographolide (or 3A.1) has been reported to be a potential anticancer agent for several types of cancer. Due to its poor aqueous solubility, 3A.1 was incorporated within self-assembly polymeric nanoparticles made of naphthyl-grafted succinyl chitosan (NSC), octyl-grafted succinyl chitosan (OSC), and benzyl-grafted succinyl chitosan (BSC). These 3A.1-loaded nanoparticles were nanosized (< 200 nm) and spherical in shape with a negative surface charge. 3A.1-loaded nanoparticles were produced using a dropping method, which 40% initial drug adding exhibited the highest entrapment efficiency. The release of 3A.1 from the 3A.1-loaded nanoparticles displayed a delayed release pattern. Under acidic conditions (pH 1.2), there was no free drug release. After the pH was adjusted to 6.8, a high cumulative 3A.1 release was obtained which was dependent on the hydrophobic moieties. These 3A.1-loaded pH-sensitive nanoparticles proved to be beneficial for specifically delivering anticancer drugs to the targeted colon cancer sites. In vitro anticancer activity against HT-29 found that the 3A.1-loaded nanoparticles had significantly lower IC than that of the free drug and promoted apoptosis. Additionally, in vitro wound-healing migration on HN-22 revealed that free 3A.1 and the 3A.1-loaded nanoparticles inhibited cell motility compared with untreated cells. These pH-sensitive amphiphilic chitosan nanoparticles may be promising nanocarriers for oral anticancer drug delivery to colorectal cancer cells. Graphical abstract ᅟ.

Development of Polymer-Assisted Nanoparticles and Nanogels for Cancer Therapy: An Update

“…MET-PLGA-PEG NPs also induced nuclei fragmentation and apoptosis in the treated cancer cells [122]. Other NPs which were reported to induce apoptosis in cancer cells are Nos-mPEG-PLGA NPs [117], NVA polymeric NPs [136], ANZ-PLNP NPs [118], 3A.1-loaded pH-sensitive NPs [132], CS-CPT-NPs [133], 5FU-Chrysin-PLGA-PEG-PLGA NPs [120], and Gemcitabine-loaded NPs conjugated with linoleic acid [143]. Nos-mPEG-PLGA NPs [117] has antiangiogenic properties while NVA polymeric NPs [136] inhibited cellular proliferation.…”

“…The enhanced drug delivery of quercetin to the target site was attributed to the improved encapsulation and the sustained release of the drug [131]. Similarly, 3A.1-loaded pH-sensitive chitosan NPs [132] and Cs-CPT NPs [133] specifically targeted and delivered the drugs to colon cancer cells. SVCSNPs was shown to exhibit controlled release of SV, hence increasing the accumulation of drug in intracellular compartments of hepatic cancer cells [134].…”

Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective

“…56 An andrographolide derivative, 19-tertbutyldiphenylsilyl-8, loaded by nanoparticles-17-epoxyandrographolide (3A.1), had a remarkably lower IC 50 than 3A.1 in HT 29 cells. 60 Liposomal andrographolide dry powder inhalers exhibited stronger activity against Staphylococcus aureus pneumonia than mere andrographolide in rats. 19 Similarly, the antipneumonic activity of andrographolide-βcyclodextrin inclusion complex (AG-β-CD) was better than andrographolide in a pneumonic rat model.…”

“…Encapsulated andrographolide in nanoparticle form was better at treating OVA‐induced asthmatic mice than its no dosage form 56 . An andrographolide derivative, 19‐tert‐butyldiphenylsilyl‐8, loaded by nanoparticles‐17‐epoxyandrographolide (3A.1), had a remarkably lower IC 50 than 3A.1 in HT 29 cells 60 . Liposomal andrographolide dry powder inhalers exhibited stronger activity against Staphylococcus aureus pneumonia than mere andrographolide in rats 19 .…”

Approaches to Improve Solubility, Stability and the Clinical Potential of Andrographolide: A Review

“…15 The Anticancer activity of AGL was observed by the induction of apoptosis. 16 Chao et al reported that down-regulation of cell growth, apoptosis, anti-angiogenesis, and anti-transformation is the major pathway of AGL to inhibit cancer cell growth. 17 Lim et al exhibited that down-regulation of tyrosine kinase, cyclin kinase, and growth factor and up-regulation of Apoptotic protein is the potential mechanism of AGL against cancerous cells.…”