Preparation and investigation of indirubin-loaded SLN nanoparticles and their anti-cancer effects on human glioblastoma U87MG cells.

Indirubin, an ingredient in traditional Chinese medicine, is considered as an anti-cancer agent. However, due to its hydrophobic nature, clinical efficiency has been limited. Drug delivery via nanotechnology techniques open new windows toward treatment of cancerous patients. Glioblastoma multiforme (GBM) is the most severe and common type of brain primary tumors. Of common problems in targeting therapies of glioblastoma is the availability of drug in tumoric tissues. In this study, Indirubin loaded solid lipid nanoparticles were prepared and their therapeutic potentials and antitumoric effects were assessed on GBM cell line (U87MG). The SLNs were prepared with Cetyl palmitate and Polysorbat 80 via high-pressure homogenization (HPH) methods in hot mode. Then, properties of SLNs including size, zeta potential, drug encapsulation efficacy (EE %) and drug loading were characterized. SLNs morphology and size were observed using SEM and TEM. The crystalinity of formulation was determined by different scattering calorimetry (DSC). The amount of drug release and antitumor efficiency were evaluated at both normal brain pH of 7.2 and tumoric pH of 6.8. The prapared SLNs had mean size of 130 nm, zeta potential of -16 mV and EE of 99.73%. The results of DSC showed proper encapsulation of drug into SLNs. Drug release assessment in both pH displayed sustain release property. The result of MTT test exhibited a remarkable increment in antitumor activity of Indirubin loaded SLN in comparison with free form of drug and blank SLN on multiform GB. This study indicated that Indirubin loaded SLNs could act as a useful anticancer drugs.

Experimental study and simulation of 63Zn production via proton induce reaction.

The 63Zn was produced by16.8 MeV proton irradiation of natural copper. Thick target yield for 63Zn in the energy range of 16.8 →12.2 MeV was 2.47 ± 0.12 GBq/µA.h. Reasonable agreement between achieved experimental data and theoretical value of thick target yield for 63Zn was observed. A simple separation procedure of 63Zn from copper target was developed using cation exchange chromatography. About 88 ± 5% of the loaded activity was recovered. The performance of FLUKA to reproduce experimental data of thick target yield of 63Zn is validated. The achieved results from this code were compared with the corresponding experimental data. This comparison demonstrated that FLUKA provides a suitable tool for the simulation of radionuclide production using proton irradiation.

Assessment of the direct cyclotron production of (99m)Tc: An approach to crisis management of (99m)Tc shortage.

Nowadays, the cyclotron production of technetium-99m ((99m)Tc) has been increased, due to the worldwide (99m)Tc generator shortage. In the present work, an improved strategy for the production of (99m)Tc, using the proton irradiation of the enriched (100)Mo was developed. The performance of this method in terms of the production yield, chemical purity, radiochemical purity, as well as radionuclide purity was evaluated. The average production yield was measured to be 356MBqµA(-1)h(-1). A good agreement was found between the calculated production yield and the experimental one. The radiochemical separation and total recovery yields of (99m)Tc were 92% and 69%, respectively. The radiochemical and the radionuclide purities of the (99m)Tc were 99% and >99.99% at the end of purification, respectively. The results of quality control tests (QC) support the concept that cyclotron-produced (99m)Tc is suitable for preparation of USP-compliant.

Development of novel biocompatible hybrid nanocomposites based on polyurethane-silica prepared by sol gel process.

Due to high biocompatibility, polyurethane has found many applications, particularly in development of biomedical devices. A new nanocomposite based on thermoset polyurethane and silica nanoparticles was synthesized using sol-gel method. Sol-gel process was fulfilled in two acidic and basic conditions by using tetraethylorthosilicate (TEOS) and trimethoxyisocyanatesilane as precursors. The hybrid films characterized for mechanical and surface properties using tensile strength, contact angle, ATR-FTIR and scanning electron microscopy. Biocompatibility and cytotoxicity of the hybrids were assessed using standard MTT, LDH and TUNEL assays. The results revealed that incorporation of silica nanoparticles was significantly improved tensile strength and mechanical properties of the hybrids. Based on the contact angle results, silica nanoparticles increased hydrophilicity of the hybrids. Biocompatibility by using human lung epithelial cell line (MRC-5) demonstrated that the hybrids were significantly less cytotoxic compared to pristine polymer as tested by MTT and LDH assays. TUNEL assay revealed no signs of apoptosis in all tested samples. The results of this study demonstrated that incorporation of silica nanoparticles into polyurethane lead to the enhancement of biocompatibility, indicating that these hybrids could potentially be used in biomedical field in particular as a new coating for medical implants.

Radiosynthesis and Quality Control of [(67)Ga]-3,4-dimethoxylated Porphyrin Complex as a Possible Imaging agent.

Radiolabeled porphyrins are potential tumor avid radiopharmaceuticals because of their impersonation in the human body, ability to complex various radionuclides, water solubility, low toxicity etc. In this work a radiogallium porphyrin complex has been developed. [(67)Ga] labeled 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin ([(67)Ga]-TDMPP) was prepared using freshly prepared [(67)Ga]GaCl3 and 5,10,15,20-tetrakis(3,4-dimethoxyphenyl) porphyrin (H2TDMPP) for 60 min at 100°C. Stability of the complex was checked in final formulation and human serum for 24 h, followed by biodistribution and imaging studies in wild type rats up to 24 h. The radiocomplex was obtained with radiochemical purity >99% (ITLC) and >98% (HPLC), specific activity: 12-15 GBq/mmol. The partition coefficient was determined (log P=1.63). A detailed comparative pharmacokinetic study performed for (67)Ga cation and [(67)Ga]-TDMPP. The complex was mostly washed out from the circulation through kidneys. Myocardial uptake was significantly observed by SPECT and biodistribution studies. Knee and shoulder joints demonstrated significant activity uptake in 2h post injection. Higher water solubility of the complex due to ionic nature of the complex is an advantage for rapid wash-out of the complex from the system, the complex has significant joint uptake compared to other radiolabeled porphyrins which the mechanisms are explained.

Development of a (68)Ga-Fluorinated Porphyrin Complex as a Possible PET Imaging Agent.

AIM: Due to the interesting pharmacologic properties of porphyrins, the idea of developing a possible tumor imaging agent using PET by incorporating (68)Ga into a suitable porphyrin ligand was investigated. METHODS: (68)Ga-labeled 5,10,15,20-tetrakis(pentafluoro-13 phenyl) porphyrin ((68)Ga-TFPP) was prepared using freshly eluted [(68)Ga]GaCl3 obtained from a 68Ge/68Ga generator developed in-house and 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin (H2TFPP) for 60 min at 100°C. RESULTS: The complex was prepared with high radiochemical purity (>99% ITLC, >99% HPLC, specific activity: 13-14 GBq/mmol). Stability of the complex was checked in the final formulation and in human serum for 5 h. The partition coefficient was calculated for the compound (log P = 0.62). The biodistribution of the labeled compound in vital organs of Swiss mice bearing fibrosarcoma tumors was studied using scarification studies and SPECT imaging up to 1 h. The complex was mostly washed out from the circulation through kidneys and liver. The tumor-to-muscle ratio 1 h post injection was 5.13. CONCLUSION: The radiolabeled porphyrin complex demonstrated potential for further imaging studies in other tumor models.

Development of ga-67 maltolate complex as an imaging agent.

Due to the antitumor activity of Gallium MAL complex, as well as recent findings on new targeted biomolecules in malignant cells through this complex, the development of radiolabeled gallium complex for future imaging studies was targeted. Ga-67 labeled 3-hydroxy-2-methyl-4H-pyran-4-onate (Ga-67 MAL) was prepared using freshly prepared Ga-67 chloride and 3-hydroxy-2-methyl-4H-pyran-4-onate in a sodium salt form in 25 min at 40° C. The stability of the complex was checked in final formulation and human serum for 24 h followed by the administration in Swiss mice for biodistribution studies. The complex was prepared in high radiochemical purity (> 97% ITLC, > 98% HPLC) and specific activity of 13-14 GBq/mmol and was stable in the presence of serum for 48 h. The partition coefficient was calculated for the compound (log p = 0.40). A detailed comparative pharmacokinetic study was performed for Ga-67 cation and Ga-67-MAL. The complex is more rapidly washed out from the circulation through kidneys and liver compared to Ga-67 cation and can be an interesting tumor imaging agent due to the fact that the cold compound is undergoing clinical trials as a safe and potential therapeutic agent for cancer.