5TH International Congress on Technology - Engineering & Science - Kuala Lumpur - Malaysia (2018-02-01)

Biocompatible And Biodegradable Drug Delivery System For Tumor Microenvironment-responsive Triggered Release

Nanotechnology created a revolution in medicine world. The main target of nanoparticles development was increasing the therapeutic properties of pharmaceutical components , which need to address some challenges: site-directed delivery to malignant cells without damaging normal cells, increasing drug solubility while accommodating the physicochemical properties, retaining drug for prolong release, cellular and intracellular release, biocompatibility with human body, easy elimination by renal clearance and maintaining the drug concentration in acceptable therapeutic boundary. A prototype nanoparticle can be studied in cell culture or living organism which demonstrate multiple cell uptake pathways in different scenarios. The “polymer-drug” conjugate is widely accepted and popular approach in drug delivery systems for cancer treatment. In this study, alginate based nanoparticles were synthesized as one of the most biocompatible and bioavailable nanocarriers in drug delivery systems; then nanoparticles were functionalized by polyethylene glycol in order to increase circulation time within the blood vessels. Polyethylene glycol is a biodegradable polymer which is highly used in pharmacology field as an excellent circulating agent. Cystamine dehydrochloride was introduced on surface of nanoparticles to induce stimuli responsive release within tumor cells. Conjugation of ligands on surface of nanoparticles was confirmed using FTIR, HNMR and elemental analysis. The nanoparticles size and morphology were characterized by TEM analysis. Furthermore, the release profile of drug was investigated in stimulated physiological tumor environment in PBS. The inhibition efficiency of nanoparticles against lung cancer cell line were studied in vitro. Results showed that nanoparticles were assembled with high stability and solubility at physiological environment for several months. The size of nanoparticles were about 150 nm. The nanoparticles with size of between 50-200 nm are the most appropriate nanostructures that show high affinity towards cluster receptors of cell membrane for internalization; though, the synthesized nanoparticles have desired range of nanocarriers for drug delivery. Nanoparticles demonstrated high drug loading efficiency of 92%. Results revealed that nanoparticles demonstrated high release profile of 75% in PBS pH5. Also, the release profile of drug in acidic environment was higher than blood physiological environment which confirm high drug release within tumor cells. In vitro studies revealed that, nanoparticles had tumor cell inhibition of 70% against human lung cancer cell lines during 72 h treatment with low toxicity against normal cells. The synthesized nanoparticles showed good pharmacokinetic profile in which an appropriate formulation methods were considered to apply beneficial properties of drug in cancer treatment. Hence, drug-loaded alginate micelles could be a promising drug delivery system for cancer delivery. Keywords: nano-drug delivery system, nanocarriers, cancer treatment, alginate
foozie sahne, Maedeh Mohammadi, Ghasem D. Najafpour