The effect of gamma and microwave radiation sterilization on periodontological grafts for microbiological evaluation.

Periodontological grafts are materials used in dentistry to regenerate lost gingival soft tissues or bone parts. In the case of direct contact with blood, the possibility of disease transmission from the source to the patient is high. This source can be an animal or a human. Therefore, the sterilization of grafts before implanting to the patient is of significant importance. The purpose of this study was to evaluate gamma radiation and microwave sterilization processes from microbiological and sterility perspectives and to compare the effectiveness of these two sterilization methods. Grafts were irradiated with 2, 4, 5, 10, 25 and 50 kGy doses of gamma radiation. Another group of same materials was irradiated by microwave for 1, 2, 3 and 4 min at 24,500 MHz and 900 W. Gamma radiation and microwave sterilization methods were evaluated as successful at minimum doses as 5 kGy and 3 min, respectively. Both gamma and microwave sterilization successfu lly sterilized periodontological grafts coded as PBG1, HBG1, HL1, PDG1, MBG3, MDG2 and PDG3. Moreover, microwave sterilization can be used as an alternative novel method to gamma radiation sterilization.

Diagnostic and therapeutic evaluation of folate-targeted paclitaxel and vinorelbine encapsulating theranostic liposomes for non-small cell lung cancer.

NSCLC is the most common type of lung cancer. However, non-specific contrast agents, radiopharmaceuticals, and treatment methods are insufficient in early diagnosis and eradication of all tumor tissue. Therefore, the formulation of a novel, targeted, specific theranostic agents possess critical importance. In our previous study, paclitaxel and vinorelbine encapsulating, Tc-99m radiolabeled, folate targeted, nanosized liposomes were formulated and found promising due to characterization properties, high cellular uptake, and cytotoxicity. In this study, in vivo therapeutic and diagnostic efficacy of liposomal formulations were tested by biodistribution study, evaluation of tumor growth inhibition, and histopathologic examination after in vitro assays on LLC1 cells. Both actively and passively targeted liposomal formulations exhibited high cellular uptake, and co-drug encapsulating liposomes showed a greater cytotoxicity profiles than free drug combination in LLC1 cells. By the results of biodistribution studies performed in NSCLC tumor-bearing C57BL/6 mice, the uptake of radiolabeled, actively folate targeted, co-drug encapsulating liposomal formulation was found to be higher in tumor tissue when compared to non-actively targeted one. Also, more effective treatment was achieved by using folate-targeted, co-drug encapsulating liposomal formulation when compared to free drugs combination according to changes in tumor size of mice. Furthermore, liposomal formulations showed lower toxicity compared to free drug combinations in the toxicity study considering body weight. Moreover, according to the histopathological study, folate targeted, co-drug encapsulating liposomes not only inhibited the tumor growth effectively but also restricted the lung metastasis entirely.

The Formulation of Methylene Blue Encapsulated, Tc-99m Labeled Multifunctional Liposomes for Sentinel Lymph Node Imaging and Therapy.

OBJECTIVES: Methylene blue (MB) is a commonly used dye that can be used for near-infrared (NIR) imaging and photodynamic therapy (PDT) by producing reactive oxygen species after light exposure, inducing apoptosis. The limiting factor of MB is its poor penetration through cell membranes. Its decreased cellular uptake can be prevented by encapsulation in drug delivery systems such as liposomes. Additionally, the enhanced permeability and retention effect of tumors enables enhanced accumulation of nanocarriers at the target site. MATERIALS AND METHODS: Nanosized, MB encapsulated, Tc-99m radiolabeled Lipoid S PC:PEG2000-PE:Chol: DTPA-PE and DPPC:PEG2000-PE:Chol:DTPA-PE liposomes were formulated to design multifunctional theranostic nanocarriers for: 1) NIR imaging, 2) gamma probe detection of sentinel lymph nodes (SLNs), and 3) PDT, which can provide accurate imaging and therapy helping surgery with a single liposomal system. The characterization of liposomes was performed by measuring particle size, zeta potential, phospholipid content, and encapsulation efficiency. Additionally, the in vitro release profile of MB and physical stability were also evaluated over 6 months at determined time intervals by measuring the mean particle size, zeta potential, encapsulation efficiency, and phospholipid content of liposomes kept at room temperature (25°C) and 4°C. RESULTS: Tc-99m radiolabeled, nanosized Lipoid S PC:PEG2000-PE:Chol:DTPA-PE and DPPC:PEG2000-PE:Chol:DTPA-PE liposomes showed suitable particle size (around 100 nm), zeta potential (-9 to -13 mV), encapsulation efficiency (around 10%), phospholipid efficiency (around 85-90%), and release profiles. Additionally, the liposomes found stable for 3 months especially when kept at 4°C. CONCLUSION: MB encapsulated, Tc-99m radiolabeled, nanosized Lipoid S PC:PEG2000-PE:Chol:DTPA-PE and DPPC:PEG2000-PE:Chol:DTPA-PE liposomes were found to have potential for SLN imaging by gamma probe detection, NIR imaging, and PDT. In vitro and in vivo imaging and therapeutic efficiency should be definitely evaluated to enable a final decision and our studies on this research topic are continuing.

Effect of X-Ray Irradiation on Some Analgesics, Anti-Diabetics, PPI'S, Anti-Hypertensives, Heart Failure Drugs in Tablet and Capsule Forms.

X-ray is an ionizing-radiation and it has been used in many processes due to the developing technology. For security purposes, X-ray instruments are been using at the entrance of the airports, shopping centers, etc. In this study, potential effects of X-ray were investigated on five different types of drugs: analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), proton pump inhibitors (lansoprazole, pantoprazole sodium sesquihydrate), anti-diabetics (metformin HCl, pioglitazone), heart failure drugs (verapamil HCl, spironolactone) and anti-hypertensives (losartan, clopidogrel hydrogen sulphate) by several different methods. In our previous study these drugs were analyzed by ESR before and after X-ray irradiation (0,24; 1,2; 58 mGy). According to the ESR results, acetylsalicylic acid tablets were affected after 58 mGy irradiation due to coated polymer (HPMC). In conclusion, these drugs were investigated before and after 0,24; 1,2 and 58 mGy X-ray irradiation by UV-spectrophotometry, dissolution test, SEM, FT-IR, DSC/TGA in this article. As a result of this study, X-ray did not cause a significant effect on drugs generally. Only a few significant differences were detected by different studies (for metformin HCl by DSC/TGA, for acetylsalicylic acid by dissolution test, and for acetaminophen and acetylsalicylic acid by UV spectrophotometry were detected significantly difference before and after irradiation).

ESR INVESTIGATIONS of X-RAY EXPOSED DRUGS.

X-ray is used in several areas for analysis, imaging, sterilisation and security. X-ray machines are increasingly used in the entrance of the airports, shopping centres, etc. for security purposes. Therefore, human beings and belongings are frequently exposed to X-ray by transiting these checkpoints at various sites such as airports, shopping centres etc. This study aims is to investigate the X-rays potential effects (arising from security machines) on different groups of medicines which are analgesics (acetaminophen, acetylsalicylic acid, naproxen, flurbiprofen), anti-diabetics (metformin HCl, pioglitazone), PPI's (lansoprazole, pantoprazole sesquihydrate), anti-hypertensives (losartan, clopidogrel hydrogen sulphate), heart failure medicines (verapamil HCl, spironolactone) used frequently and daily, by using ESR analysis. Coated acetylsalicylic acid tablets showed different intensities of ESR signals after 58 mGy irradiation. It thought to be the result of the coating polymer (Hydroxypropylmethylcellulose (HPMC)). According to the ESR results which were obtained for 0,24-58 mGy irradiated drugs- 1 hour after irradiation (refrigerated during this period) X-ray did not affect those medicines except the acetylsalicylic acid tablets significantly. The meaningful differences were only obtained between the non-irradiated, and 58 mGy irradiated acetylsalicylic acid tablets. Therefore, it can be concluded that X-ray exposed medicines, except coated acetylsalicylic acid tablets (after 58 mGy irradiation), can be used safely for the irradiation levels used in this study (0.24 mGy-0.58 mGy). In addition those data, ESR analyses were followed by other analysis such as FT-IR, DSC/TGA, dissolution, SEM, etc., and they are planned to be published soon.

Targeted Alpha Therapy and Nanocarrier Approach.

The rates of cancer incidence and mortality are increasing day by day. Although several conventional methods including surgery, chemotherapy, and radiotherapy (RT) exist for cancer treatment, they are insufficient in the eradication of all tumor tissues and have some side-effects such as narrow therapeutic index and serious side-effects to healthy tissues. Moreover, it may probably recur in time due to the survival and spreading of cancerous cells or any possible metastases. Targeted radionuclide therapy is a promising alternative. α particles are ideal for localized cell killing because of their high linear energy transfer and short ranges. However, upon emission of α particles, the daughter nuclides induce a recoil energy to lead decoupling from any chemical bond that may accumulate in normal tissues. Targeted α therapy can also be performed by targeted delivery systems apart from mAb, mAb fragments, peptides, and small molecules for selective tumor therapy. Targeted drug delivery systems have been developed to overcome the limitations of α therapy. Moreover, drug delivery systems are one of the most searched applications in cancer imaging and/or treatment due to their targeting ability to tumor or biocompatibility properties. The aim of this article is to summarize tumor therapy applications, targeted α RT approach, and to review the role of drug delivery systems in the delivery of α particles for cancer therapy and some instances of targeted α-emitting drug delivery systems from the literature.

99mTc-radiolabeled Levofloxacin and micelles as infection and inflammation imaging agents.

Easy and early detection of infection and inflammation is essential for early and effective treatment. In this study, PEGylated micelles were designed and both micelles and Levofloxacin were radiolabeled with 99mTcO4 - to develop potential radiotracers for detection of infection/inflammation. Radiolabeling efficiency, in vitro stability and bacterial binding of 99mTc-Levofloxacin and 99mTc-micelles were compared. The aim of this study is to formulate and compare 99mTc-Levofloxacin and 99mTc-micelles as infection and inflammation agents having different mechanisms for the accumulation at infection and inflammation site. PEGylated micelles were designed with a particle size of 80 ± 0.7 nm and proper characterization properties. High radiolabeling efficiency was achieved for 99mTc-Levofloxacin (96%) and 99mTc-micelles (87%). The radiolabeling efficiency was remained stable with some insignificant alterations for both radiotracers at 25 °C for 24 h. Although in vitro bacterial binding of 99mTc-levofloxacine was higher than 99mTc-micelles, 99mTc-micelles may also be evaluated potential agent due to long circulation and passive accumulation mechanisms at infection/inflammation site. Both radiopharmaceutical agents exhibit potential results in design, characterization, radiolabeling efficiency and in vitro bacterial binding point of view.

Clinical Applications of Nanosized Drug-Delivery Systems in Lung Cancer Imaging and Therapy.

Globally, lung cancer is one of the most frequently diagnosed and deadliest types of cancer. Lung cancer imaging can be performed using both invasive and noninvasive techniques, including magnetic resonance, positron emission tomography, single photon emission computed tomography, chest radiography, and computed tomography. But nonspecific contrast agents and radiopharmaceuticals are insufficient for early and specific diagnoses and imaging. In the case of lung cancer therapy, conventional therapeutic agents and radiotherapy may cause severe and systemic adverse and toxic effects and fail to eradicate all tumor tissue. Therefore, formulation of novel, targeted, and specific agents is critically important to overcome these challenges. In this review, we summarize lung cancer classification, current methods for lung cancer imaging and therapy, and future options containing nanosized systems for lung cancer imaging and/or therapy.

Near-infrared imaging of diseases: A nanocarrier approach.

Developments in fluorescence imaging, brought popularity to near infrared (NIR) imaging with far-red and NIR fluorophores applied for biosensing and bioimaging in living systems. Noninvasive NIR imaging gained popularity with the use of effective NIR dyes to obtain macroscopic fluorescence images. Several attributes of NIR dyes make them desirable agents, including high specificity, high sensitivity, minimized background interference, and the ability to easily conjugate with drug delivery systems. However, NIR dyes have some drawbacks and limitations, such as low solubility, low stability, and degradation. To overcome these issues, NIR dyes can be encapsulated in appropriate nanocarriers to achieve effective diagnosis, imaging, and therapy monitoring during surgery. Moreover, the vast majority of NIR dyes have photosensitizer features that can effectuate cancer treatment referred to as photodynamic therapy (PDT). In the near future, by combining NIR dyes with appropriate nanocarriers such as liposomes, polymeric micelles, polymeric nanoparticles, dendrimers, quantum dots, carbon nanotubes, or ceramic/silica based nanoparticles, the limitations of NIR dyes can be minimized or even effectively eliminated to form potential effective agents for imaging, therapy, and therapy monitoring of several diseases, particularly cancer.

Theranostic polymeric nanoparticles for NIR imaging and photodynamic therapy.

Near-Infrared (NIR) dyes forming some of the photosensitizer agents show imaging and therapy features by themselves. NIR dyes show photodynamic therapy by formation of reactive oxygen species and imaging by NIR Fluorescence light. Photodynamic therapy occurs from irradiation of laser or light to photosensitizer matters and following by the formation of reactive oxygen species diseased tissues or cells can be killed effectively. NIR dyes have advantages such as stability, high specificity and sensitivity when compared with the other photosensitizer and imaging agents. Drug delivery systems are getting attention for either diagnosis or therapy of almost all of the diseases. Theranostic nanoparticles comprise the substances which shows the imaging and treatment features together. Besides, the combination of active substance and the imaging agent can also be encapsulated in theranostic nanoparticles. Many researchs are performed to evaluate the efficacy of theranostic drug delivery systems particularly polymeric nanoparticles in order to enhance targeting properties, specificity and bioavailability. Polymeric nanoparticles give advantages because of easier degradation properties when compared with the others. Theranostic polymeric nanoparticles can be used for NIR imaging and photodynamic therapy of several diseases especially cancers.

Current and Future Approaches for Effective Cancer Imaging and Treatment.

Cancer poses a major health problem, not only due to cancer-related deaths but also because of treatment toxicities. This review discusses early diagnosis and strategies to overcome treatment difficulties, to facilitate recovery, and prevent deaths. Generally, noninvasive techniques such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT) and positron emission computed tomography (PET), and their hybrid systems, including SPECT/CT, PET/CT, and PET/MRI, are used in diagnosis of cancer. Cancer treatment in clinics still comprises conventional methods such as chemotherapy, radiotherapy, and surgery. However, these techniques and methods are often inadequate. Therefore, new approaches, including the formulation of actively and/or passively targeted nanosized drug delivery systems and combined treatment protocols, are being investigated. In this article, conventional cancer imaging and treatment are reviewed. In addition, the formulation of nanosized systems and their use in cancer treatment are discussed and combined diagnostic and therapeutic (theranostic) approach are proposed as additional cancer therapies.