Search

Mehdi Abedi,1 Samira Sadat Abolmaali,1,2 Mozhgan Abedanzadeh,1 Fatemeh Farjadian,2 Soliman Mohammadi Samani,2,3 Ali Mohammad Tamaddon1,2 1Department of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, Iran; 2Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, Iran; 3Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, IranCorrespondence: Ali Mohammad TamaddonDepartment of Pharmaceutical Nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Fars, IranTel +98 71 32424126Email amtamadon@gmail.comIntroduction: As widely used chemotherapeutic agents, platinum compoundshave several therapeutic challenges, such as drug resistance and adverse effects. Theranostic systems, macromolecular or colloidal therapeutics with companion diagnostics, not only address controlled drug delivery but also enable real-time monitoring of tumor sites.Methods: Synthesis of magnetic mesoporous silica nanoparticles (MMSNs) was performed for dual magnetic resonance imaging and drug delivery. MMSN surfaces were modified by imidazoline groups (MMSN-Imi) for cisplatin (Cis-Pt) conjugation via free N-termini to achieve well-controlled drug-release kinetics. Cis-Pt adsorption isotherms and drug-release profile at pH 5 and 7.4 were investigated using inductively coupled plasma atomic emission spectroscopy.Results: MMSN-Imi showed a specific surface area of 517.6 m2 g− 1, mean pore diameter of 3.26 nm, and saturated magnetization of 53.63 emu/g. A relatively high r2/r1 relaxivity value was obtained for MMSN-Imi. The nanoparticles provided high Cis-Pt loading with acceptable loading capacity (∼ 30% w:w). Sustained release of Cis-Pt under acidic conditions led to specific inhibitory effects on the growth of human epithelial ovarian carcinoma cells, determined using MTT assays. Dual acridine orange–propidium iodide staining was investigated, confirming induction of apoptosis and necrotic cell death.Conclusion: MMSN-Imi exhibited potentialfor applications in cancer chemotherapy and combined imaging.Keywords: magnetic properties, cisplatin, SiO2, theranostic, MRI, drug delivery

Purpose: Due to limited oral bioavailability of doxorubicin (Dox) many efforts during the last decades focused on the development of novel delivery systems to overcome these limitations. In the present study, Dox encapsulated chitosan nanoparticles were prepared to evaluate the intestinal permeation of Dox via oral administration. Methods: Nanoparticles were fabricated based on ionic gelation method using tripolyphosphate. Some physicochemical properties, such as nanoparticle size and morphology, loading efficiency and in vitro drug release in 3 different pH values (5.0, 6.8 & 7.4) were evaluated. Intestinal permeations of free Dox and Dox loaded in nanoparticles were assessed using rat intestinal sac model. Results: The nanoparticles were spherical shape with average size of 150 ± 10 nm. The entrapment and loading efficiency of Dox were up to 40% and 23%, respectively. According to the release profiles, up to 30% of loaded drug was released within 6hrs and the remaining amount of Dox was released more gradually, but this pattern was related to pH of the medium. The amount of drug released at acidic condition (pH 5.0) was greater than other pHs. The intestinal permeation of Dox increased nearly up to 90% by loading in chitosan nanoparticles. Conclusion: Using chitosan nanoparticles presents a potential safe drug delivery system for oral administration of Dox. In vivo studies and the determined pharmacokinetic and pharmacodynamic of Dox loaded chitosan nanoparticles after oral administration are planned for future studies.