Chitosan/nialfe-ldh composite: a ph-responsive bio-carrier of curcumin release for treatment of breast cancer
,1 Ali reza mahjoub
1. Tarbiat Modares University
2. Tarbiat Modares University
In the treatment of cancer, drug delivery plays a fatal role. however, it is essential to control the release of drug from drug delivery systems since very low drug concentrations are not therapeutically effective and very high dosages lead to cellular toxicity. though curcumin presents many pharmaceutical activities, its application is limited due to its low water solubility, high rate of decomposition at neutral ph and susceptibility to photochemical degradation, which result in its low bioavailability.
some potential drug delivery materials include luminescent rare-earth compounds, mesoporous silica, hydroxyapatite, metal oxides and metal hydroxides. among these materials, layered double hydroxides (ldhs) have attracted much interest since they can be utilized for catalysis, sensor and biomedical purposes. the high surface area, great pore volume and uniform pore size of ldhs represent them as a suitable candidate for drug delivery. the problem is that ldhs are hydrophilic and toxic. moreover, the ph of cancerous cells is about 5.5 to 5.8 while the ph of normal cells is 7.4. therefore, the devised drug carrier should be ph-responsive to minimize the side effects of the loaded drug. in this respect, chitosan can be applied since it is biodegradable, biocompatible and ph-responsive and it can be coated on ldh to load curcumin.
Methyl thiazolyl tetrazolium (mtt) assay was performed to investigate cytotoxicity of the bio-carrier against the mcf-7 human breast cancer cell line. about 5120 cells were seeded into 96-well plates at 37 ℃ under a 5% co2 atmosphere. 0, 5, 10, 20 40, 80 and 200 mg/ml of the curcumin loaded carrier was added to the wells and the plates were incubated for 24 h. after that, 10 ml mtt (5 mg/ml) was injected to each well and the plates were incubated for 3 h. this treatment resulted in the formation of purple formazone crystals, which were dissolved in 100 ml dmso. after that, absorbance of the wells was recorded at 570 nm by a multi-well elisa plate reader to estimate their cell viability (%) as (asample/acontrol)×100, where asample and acontrol are absorbances of the treated and untreated wells, respectively.
After detailed characterization of the bio-carrier, its drug delivery performance was evaluated. as the first measure, its ph response was studied since normal extracellular ph is about 7.4 but tumorous tissues are slightly acidic (ph≈0.5). the release behavior of curcumin is considerably ph sensitive. so that, just 23.7% curcumin releases at ph 7.4 whereas about 93.5% release is observed at ph 5.0, within 4 days.
dpph assay was adopted to investigate the overall anti-oxidant capacity of curcumin@chitosan/nialfe-ldh, chitosan/nialfe-ldh and chitosan. the associated results show that chitosan and the carrier possess nominal antioxidant activity while curcumin@chitosan/nialfe-ldh is able to scavenge radicals and act as a good antioxidant. in this respect, 150 μl curcumin@chitosan/nialfe-ldh gave 92% scavenging activity and the level of activity remained almost constant using 200 μl curcumin@chitosan/nialfe-ldh.
mtt assay was conducted to investigate biocompatibility of the chitosan/nialfe-ldh bio-carrier. compared with the control group, cellular viability is greater than 90%, in the presence of chitosan/nialfe-ldh. it means that cytotoxicity of this carrier is insignificant and it can be used as a biocompatible and biodegradable drug delivery system. meantime, it is evident that this carrier is cytotoxic for the mcf7 cells and its corresponding inhibitory concentration at 50% (ic50) is 20 mg/ml. this finding suggests that the proposed composite is applicable to long-term and target-specific treatment of human tumors.
This study reports synthesis and characterization of chitosan/nialfe-ldh bio-carriers, as a mesoporous hydrophilic drug delivery system for treatment of breast cancer by curcumin. the results demonstrated that the drug release profile of chitosan/nialfe-ldh is ph sensitive. so that, it can release a noticeable amount of the loaded drug at ph 5.0 while it releases a negligible amount of the drug at ph 7.4. in addition to its ph-responsive property, the drug loaded carrier was approved to act as an antioxidant agent with low cytotoxicity against normal cells and high cytotoxicity against the mcf7 cell line. in general, the introduced carrier is appropriate for long-term release and target specific cancer therapy.
Chitosan/nialfe-ldh bio-carrier; ph-responsive; biomaterials; curcumin; breast cancer cell line.