Our objective of this study is to design and develop a polyethylene glycol ( PEG2000)-modified multiwall carbon nanotube (PEGylated MWCNT) formulation for oral controlled metronomic chemotherapeutic drug delivery. Multiwall carbon nanotubes undergo various chemical modifications including oxidation with strong acids, conjugation of polyethylene glycol, and coating with cellulose acetate phthalate which resulted in the formation of aqueous dispersion and prevention of drug degradation in acidic environment. Advanced analytical procedure such as Fourier transform infra-red, X-ray diffraction, differential scanning calorimetry, thermal gravimetric analysis, transmission electron microscopy, and dynamic light scattering techniques were used to evaluate physicochemical characterization. We also performed in vitro cytotoxic study by MTT assay and results revealed that carboplatin-loaded PEGylated MWCNTs did not show significant detrimental effect on the viability of MDA-MB-231 (human breast cancer) cells. The maximum encapsulation and drug-loading capacity were determined to be 71.58 ± 0.04 and 39.62 ± 0.07%, respectively. The release of carboplatin from PEGylated MWCNTs was investigated at simulated intestinal fluid (SIF), pH 6.8, after optimizing at simulated gastric fluid (SGF), pH 1.2, by enteric coating. Enteric-coated PEGylated MWCNTs exhibit pH-responsive drug activity in a sustained manner especially at pH 6.8. This surface modification strongly suggests that PEGylated MWCNTs could be a potential carrier for metronomic chemotherapeutic agent for high drug resistance, drug with maximum adverse effect and poorly oral bioavailable drugs.

Photodynamic therapy(PDT) is recently developed as an effective treatment for malignant disease. Carboplatin, a less nephrotoxic analog of cisplatin, has been widely used for the treatment of multiple malignancies. In this study, we investigated the cytotoxic and apoptotic effect of combined modality of photofrin mediated PDT with cisplatin and carboplatin on KB cell human oral cancer cell line in vitro. The a ttached KB cells were incu bated with c isplatin(0.04mg/ml) and carboplatin(0.02mg/ml) for 24h at 37℃ and followed by photosensitization with photofrin for 6h and laser irradiation with 630nm LED at an intensity of 2.0 J/cm2 for activating photofrin for 15min. Then MTT assay and SYTO 16 green & Propidium iodide (PI) double staining were used respectively to measure the cytotoxicity and nuclear morphology at 24h after PDT. This study demonstrates that the combined modality with carbopaltin resulted in enhanced apoptotic cell death as well as cytotoxic e ffect on KB c ells in vitro, which s uggests the feasibility of combined modality and the possibility o f reducing the effective dosage of photofrin and carboplatin and lowering the side effects on normal cells