Asia-Pacific Journal of Oncology

Research Article | Open Access

Fabrication and bioactivity evaluation of curcumin and paclitaxel loaded lipid nanoparticles of pH-sensitive histidinylated cationic amphiphile

Swathi Vangala1, 2, Gopikrishna Moku1, 3

1Applied Biology Division, CSIR-Indian Institute of Chemical Technology (CSIR-IICT), Tarnaka, Uppal Road, Hyderabad 500 007, India.

2Telangana Social Welfare Residential Degree College for Women, Bhupalapally 506 169, Telangana, India.

3Department of Physical Sciences, Kakatiya Institute of Technology and Science, Yerragattu Gutta, Warangal 506 015, Telangana, India.

Correspondence: Gopikrishna Moku (Department of Physical Sciences, Kakatiya Institute of Technology and Science, Yerragattu Gutta, Warangal 506 015, Telangana, India; Email: gopikrishna.moku@gmail.com; mgkr.pss@kitsw.ac.in).

Asia-Pacific Journal of Oncology 2021, 2: 7-16. https://doi.org/10.32948/ajo.2021.04.06

Received: 10 Mar 2021 | Accepted: 03 Apr 2021 | Published online: 15 Apr 2021

Abstract
Drug resistance, inefficient cellular uptake and the subservient drug release to increase the intracellular drug concentration inside the tumor cells are the key reasons for low therapeutic efficacy of drug-loaded lipid nanoparticles in cancer therapy. Herein, we report on the design, synthesis and bioactivity evaluation of Curcumin & Paclitaxel (PTX) encapsulated endosomal pH-Sensitive lipid nanoparticles of histidinylated cationic amphiphile (16-GH; 2 in 1 system) to overcome these challenges. Findings in fluorescence resonance energy transfer (FRET) assay and in vitro drug release studies showed a controlled pH dependent fusogenic and drug release properties of the lipid nanoparticles of cationic amphiphile 16-GH respectively. Further in vitro studies revealed that Curcumin & PTX encapsulated nanoparticles of lipid 16-GH significantly inhibited proliferation of tumor cells than healthy cells. These lipid nanoparticles were further analyzed for their effect on 5-bromo-2'-deoxyuridine (BrdU) incorporation, Annexin V-FITC and cell cycle arrest (Sub-G1 phase). Further studies also confirmed that nanoparticles of lipid 16-GH containing Curcumin & PTX displayed significantly enhanced the caspase3/9 activity. Remarkably, nanoparticles of lipid 16-GH containing Curcumin & PTX are efficient in inducing apoptosis. The results in our initial mechanistic studies support the notion that the tumor cell selective cytotoxic capability of the lipid nanoparticles of the presently described endosomal pH-sensitive lipid probably instigates from depolarization of mitochondrial membrane potential and subsequent activation of caspases 3 and 9. The distinguishing feature of the currently described endosomal pH-sensitive system is that it not only efficiently delivers highly potent anti-cancer agents (Curcumin & PTX) to tumor cells, but the lipid nanoparticle drug carrier itself also contributes to inhibiting tumor cell  growth. In summary, the presently described lipid nanoparticles are expected to simultaneously delivering combination of drugs to various types of tumor models.

Key words Endosomal pH-sensitivity, histidinylated cationic amphiphiles, Curcumin, paclitaxel, fusogenic lipid nanoparticles, intra cellular drug delivery