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1.
Pharmaceutics ; 16(3)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38543298

ABSTRACT

It is evident that radiolabeled drug delivery systems hold great promise in the field of lung cancer management. The combination of therapeutic agents with radiotracers not only allows for precise localization within lung tumors but also enables real-time monitoring of drug distribution. This approach has the potential to enhance targeted therapy and improve patient outcomes. The integration of advanced imaging modalities, such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT), has played a crucial role in the non-invasive tracking of radiolabeled drugs. These techniques provide valuable insights into drug pharmacokinetics, biodistribution, and tumor-targeting efficiency, offering clinicians the ability to personalize treatment regimens. The comprehensive analysis of preclinical and clinical studies presented in this review underscores the progress made in the field. The evidence suggests that radiolabeled drug delivery systems have the potential to revolutionize oncology by offering precise, targeted, and image-guided therapeutic interventions for lung cancer. This innovative approach not only enhances the effectiveness of treatment but also contributes to the development of personalized medicine strategies, tailoring interventions to the specific characteristics of each patient's cancer. The ongoing research in this area holds promise for further advancements in lung cancer management, potentially leading to improved outcomes and quality of life for patients.

2.
Int J Pharm ; 652: 123765, 2024 Mar 05.
Article in English | MEDLINE | ID: mdl-38195032

ABSTRACT

Despite the successful use of the radiopharmaceutical radium-223 dichloride ([223Ra]RaCl2) for targeted alpha therapy of castration-resistant prostate cancer patients with bone metastases, some short-term side effects, such as diarrhea and vomiting, have been documented, causing patient discomfort. Hence, we prepared a nanosized micellar solution of [223Ra]RaCl2 and evaluated its biodistribution, pharmacokinetics, and induced biochemical changes in healthy mice up to 96 h after intraperitoneal administration as an alternative to overcome the previous limitations. In addition, we evaluated the bone specificity of micellar [223Ra]RaCl2 in patient-derived xenografts in the osteosarcoma model. The biodistribution studies revealed the high bone-targeting properties of the micellar [223Ra]RaCl2. Interestingly, the liver uptake remained significantly low (%ID/g = 0.1-0.02) from 24 to 96 h after administration. In addition, the micellar [223Ra]RaCl2 exhibited a significantly higher uptake in left (%ID/g = 0.85-0.23) and right (%ID/g = 0.76-0.24) kidneys than in small (%ID/g = 0.43-0.06) and large intestines (%ID/g = 0.24-0.09) over time, suggesting its excretion pathway is primarily through the kidneys into the urine, in contrast to the non-micellar [223Ra]RaCl2. The micellar [223Ra]RaCl2 also had low distribution volume (0.055 ± 0.003 L) and longer elimination half-life (28 ± 12 days). This nanosystem was unable to change the enzymatic activities of alanine aminotransferase, aspartate aminotransferase, gamma GT, glucose, and liquiform lipase in the treated mice. Finally, microscopic examination of the animals' osteosarcoma tumors treated with micellar [223Ra]RaCl2 indicated regression of the tumor, with large areas of necrosis. In contrast, in the control group, we observed tumor cellularity and cell anaplasia, mitotic figures and formation of neoplastic extracellular bone matrix, which are typical features of osteosarcoma. Therefore, our findings demonstrated the efficiency and safety of nanosized micellar formulations to minimize the gastrointestinal excretion pathway of the clinical radiopharmaceutical [223Ra]RaCl2, in addition to promoting regression of the osteosarcoma. Further studies must be performed to assess dose-response outcomes and organ/tissue dosimetry for clinical translation.


Subject(s)
Bone Neoplasms , Osteosarcoma , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Animals , Mice , Radiopharmaceuticals/pharmacokinetics , Tissue Distribution , Renal Elimination , Bone Neoplasms/drug therapy , Bone Neoplasms/radiotherapy , Osteosarcoma/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology
3.
J Funct Biomater ; 14(9)2023 Sep 18.
Article in English | MEDLINE | ID: mdl-37754891

ABSTRACT

Breast cancer is a leading cause of cancer-related mortality among women worldwide, with millions of new cases diagnosed yearly. Addressing the burden of breast cancer mortality requires a comprehensive approach involving early detection, accurate diagnosis, effective treatment, and equitable access to healthcare services. In this direction, nano-radiopharmaceuticals have shown potential for enhancing breast cancer diagnosis by combining the benefits of nanoparticles and radiopharmaceutical agents. These nanoscale formulations can provide improved imaging capabilities, increased targeting specificity, and enhanced sensitivity for detecting breast cancer lesions. In this study, we developed and evaluated a novel nano-radio radiopharmaceutical, technetium-99m ([99mTc]Tc)-labeled trastuzumab (TRZ)-decorated methotrexate (MTX)-loaded human serum albumin (HSA) nanoparticles ([99mTc]-TRZ-MTX-HSA), for the diagnosis of breast cancer. In this context, HSA and MTX-HSA nanoparticles were prepared. Conjugation of MTX-HSA nanoparticles with TRZ was performed using adsorption and covalent bonding methods. The prepared formulations were evaluated for particle size, PDI value, zeta (ζ) potential, scanning electron microscopy analysis, encapsulation efficiency, and loading capacity and cytotoxicity on MCF-7, 4T1, and MCF-10A cells. Finally, the nanoparticles were radiolabeled with [99mTc]Tc using the direct radiolabeling method, and cellular uptake was performed with the nano-radiopharmaceutical. The results showed the formation of spherical nanoparticles, with a particle size of 224.1 ± 2.46 nm, a PDI value of 0.09 ± 0.07, and a ζ potential value of -16.4 ± 0.53 mV. The encapsulation efficiency of MTX was found to be 32.46 ± 1.12%, and the amount of TRZ was 80.26 ± 1.96%. The labeling with [99mTc]Tc showed a high labeling efficiency (>99%). The cytotoxicity studies showed no effect, and the cellular uptake studies showed 97.54 ± 2.16% uptake in MCF-7 cells at the 120th min and were found to have a 3-fold higher uptake in cancer cells than in healthy cells. In conclusion, [99mTc]Tc-TRZ-MTX-HSA nanoparticles are promising for diagnosing breast cancer and evaluating the response to treatment in breast cancer patients.

4.
Appl Radiat Isot ; 198: 110856, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37245319

ABSTRACT

The development of new drugs that can specifically screen tumors is a global need. When it comes to lung cancer, which is the second main cause of cancer-related deaths, early detection of lung tumors using appropriate imaging is very important. In this study, gemcitabine hydrochloride (GCH) was radiolabeled with [99mTc]Tc under different conditions (changing reducing agent, antioxidant agent, incubation time, pH, [99mTc]Tc activity) and radiolabeling activity (quality control) using Radio Thin Layer Chromatography and paper electrophoresis. The results showed that the most stable complex ([99mTc]Tc-GCH) was prepared using 0.015 mg of stannous chloride as a reducing agent, 0.01 mg of ascorbic acid as an antioxidant and 37 MBq activity at pH 7.4 after 15 min of incubation time. The complex remained stable for 6 h. Cell incorporation studies showed a six-fold higher uptake of [99mTc]Tc-GCH in cancer (A-549) cells (38.42 ± 1.53) than healthy (L-929) cells (6.11 ± 0.17) have shown that it can. In addition, the different behaviors of R/H-[99mTc]Tc confirmed the specificity of this newly developed radiopharmaceutical. Although these studies are preliminary, it has been concluded that [99mTc]Tc-GCH may be a candidate drug for use in nuclear medicine, particularly in the diagnosis of lung cancer.


Subject(s)
Lung Neoplasms , Technetium , Humans , Technetium/chemistry , Gemcitabine , Antioxidants , Reducing Agents , Radiopharmaceuticals/chemistry , Lung Neoplasms/diagnostic imaging , Quality Control
5.
Turk J Pharm Sci ; 20(2): 91-99, 2023 May 09.
Article in English | MEDLINE | ID: mdl-37161446

ABSTRACT

Objectives: Early detection of bone cancer is critical for treating symptoms, minimizing pain, and increasing overall quality of life. It is critical to develop novel radiopharmaceuticals with high labeling efficiency and stability for the diagnosis of bone cancer. This research aims to design a novel radiopharmaceutical that may be used to diagnose bone cancer. Materials and Methods: In this study, ibandronate sodium (IBD), a bisphosphonate analog, was radiolabeled with technetium-99m [99mTc] and quality control tests on the newly developed radiopharmaceutical ([99mTc]Tc-IBD) were performed using radioactive thin layer chromatography. After that, the incorporation of [99mTc]Tc-IBD into hydroxyapatite (HA) crystals and a human bone osteosarcoma cell line (U2OS) was tested. Results: According to the results obtained, optimal radiolabeling procedure was obtained for [99mTc]Tc-IBD with 200 µg.mL-1 IBD, 20 µg stannous chloride, and 99mTc with 37 MBq radioactivity. The reaction mixture was adjusted to pH 5.5 and incubated at room temperature for 15 min. The radiochemical purity of [99mTc]Tc-IBD was found to be greater than 95% at room temperature for up to 6 h. Additionally, chromatography analysis showed >95% [99mTc]Tc-IBD complex formation with promising stability for up to 24 h in saline and up to 2 h in cell medium. The percentage binding of IBD to HA was 83.70 ± 3.67 and the logP of [99mTc]Tc-IBD was -1.1014. The radiolabeled complex exhibited a higher rate of cell incorporation to U2OS cells compared to Reduced/Hydrolyzed 99mTcO4 -. Conclusion: The newly produced radiopharmaceutical is very promising according to the results of in vitro cell culture, HA binding, and quality studies, and will be a step forward for further studies in nuclear medicine for bone cancer diagnostics.

6.
ACS Omega ; 8(7): 6279-6288, 2023 Feb 21.
Article in English | MEDLINE | ID: mdl-36844604

ABSTRACT

The aim of this research was to develop technetium-99m ([99mTc]Tc)-radiolabeled niosomes and evaluate the cancer cell incorporation capacity of radiolabeled niosomes. For this purpose, niosome formulations were developed by film hydration method, and prepared niosomes were characterized to particle size, polydispersity index (PdI), ζ-potential value, and image profile. Then, niosomes were radiolabeled with [99mTc]Tc using stannous salts (chloride) as a reducing agent. The radiochemical purity (RP) and stability in different mediums of the niosomes were assessed by ascending radioactive thin-layer chromatography (RTLC) and radioactive ultrahigh-performance liquid chromatography (R-UPLC) methods. Also, the partition coefficient value of radiolabeled niosomes was determined. The cell incorporation of [99mTc]Tc-labeled niosome formulations, as well as reduced/hydrolyzed (R/H)-[99mTc]NaTcO4 in the HT-29 (human colorectal adenocarcinoma) cells, was then assessed. According to the obtained results, the spherical niosomes had a particle size of 130.5 ± 1.364 nm, a PdI value of 0.250 ± 0.023, and a negative charge of -35.4 ± 1.06 mV. The niosome formulations were effectively radiolabeled with [99mTc]Tc using 500 µg mL-1 stannous chloride for 15 min, and RP was found to be over 95%. [99mTc]Tc-niosomes showed good in vitro stability in every system for up to 6 h. The log P value of radiolabeled niosomes was found as -0.66 ± 0.02. Compared to R/H-[99mTc]NaTcO4 (34.18 ± 1.56%), the incorporation percentages of [99mTc]Tc-niosomes (88.45 ± 2.54%) were shown to be higher in cancer cells. In conclusion, the newly developed [99mTc]Tc-niosomes showed good prototype for potential use in nuclear medicine imaging in the near future. However, further investigations, such as drug encapsulation and biodistribution studies, should be performed, and our studies are continuing.

7.
Colloids Surf B Biointerfaces ; 223: 113174, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36746067

ABSTRACT

The use of targeted alpha therapy (TAT) for bone cancer is increasing each year. Among the alpha radionuclides, radium [223Ra]Ra+2 is the first one approved for bone cancer metastasis therapy. The development of novel radiopharmaceutical based on [223Ra]Ra+2 is essential to continuously increase the arsenal of new TAT drugs. In this study we have developed, characterized, and in vitro evaluated [223Ra] Ra-nano-hydroxyapatite. The results showed that [223Ra] Ra-nano-hydroxyapatite has a dose-response relationship for osteosarcoma cells and a safety profile for human fibroblast cells, corroborating the application as a radiopharmaceutical.


Subject(s)
Bone Neoplasms , Nanostructures , Osteosarcoma , Radium , Humans , Radiopharmaceuticals , Radium/chemistry , Radium/therapeutic use , Bone Neoplasms/drug therapy , Osteosarcoma/drug therapy
8.
ACS Omega ; 7(38): 33793-33807, 2022 Sep 27.
Article in English | MEDLINE | ID: mdl-36188287

ABSTRACT

The aim of the study was to prepare and evaluate the potential use of poly(lactic acid)/poly(vinyl alcohol) (PLA/PVA) nanoparticle formulations as a drug delivery system. The nanoparticle formulations were successfully developed by the double emulsification/solvent evaporation method. The developed formulations were optimized using the quality by design approach of the ICH Q8 (Pharmaceutical Development) guideline. In the studies, the effects of emulsifying devices, evaporation technique, centrifugation effect, and polymer concentrations on the physicochemical parameters of the formulations were investigated to obtain the best results. Furthermore, the prepared formulations were evaluated for clarity, particle size, distribution, zeta potential, surface and morphological features, preparation efficiency, and long-term stability. Based on the obtained results, the nanoparticle formulation containing 12.5% PLA, 1% primer, and seconder PVA has a suitable particle size (181.7 ± 2.194 nm) and distribution (0.104 ± 0.049), zeta potential (-0.88 ± 0.45 mV), and high preparation efficiency (65.38%), and nanoparticles were spherical, had a smooth surface, and were stable up to 12 months. In conclusion, this novel formulation can be used as a potential drug delivery system.

9.
J Pharm Biomed Anal ; 221: 115024, 2022 Nov 30.
Article in English | MEDLINE | ID: mdl-36108462

ABSTRACT

Radiopharmaceuticals are radioactive drugs, with a very short shelf life, in most of the cases. The number of proceedings using radiopharmaceuticals increases each day worldwide and for many countries the price of radiopharmaceuticals can represent a limitation in the offer of this drug for more patients. Nonetheless, the shortage of important radionuclides is a serious issue and may also affect the use and distribution of these drugs for more patients globally, especially in low and middle income countries. In this direction, the need to avoid waste of these drugs is crucial. In this study we have evaluated the stability of two radiopharmaceuticals (MDP and DTPA) under different conditions in order to propose the extension of shelf life. The results showed that is possible to have stable radiopharmaceuticals (both MDP and DTPA) even 24hs post labeling process when storage properly. The data may represent an advance in the field of Radiopharmacy, providing news perspectives for radiopharmaceuticals shelf life.


Subject(s)
Radioisotopes , Radiopharmaceuticals , Humans , Pentetic Acid
10.
Eur J Pharm Biopharm ; 180: 91-100, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36154904

ABSTRACT

The use of graphene quantum dots as biomedical devices and drug delivery systems has been increasing. The nano-platform of pure carbon has shown unique properties and is approved to be safe for human use. In this study, we successfully produced and characterized folic acid-functionalized graphene quantum dots (GQD-FA) to evaluate their antiviral activity against Zika virus (ZIKV) infection in vitro, and for radiolabeling with the alpha-particle emitting radionuclide radium-223. The in vitro results exhibited the low cytotoxicity of the nanoprobe GQD-FA in Vero E6 cells and the antiviral effect against replication of the ZIKV infection. In addition, our findings demonstrated that functionalization with folic acid doesn't improve the antiviral effect of graphene quantum dots against ZIVK replication in vitro. On the other hand, the radiolabeled nanoprobe 223Ra@GQD-FA was also produced as confirmed by the Energy Dispersive X-Ray Spectroscopy analysis. 223Ra@GQD-FA might expand the application of alpha targeted therapy using radium-223 in folate receptor-overexpressing tumors.


Subject(s)
Graphite , Quantum Dots , Zika Virus Infection , Zika Virus , Humans , Quantum Dots/chemistry , Graphite/chemistry , Folic Acid/chemistry , Antiviral Agents/pharmacology
11.
Eur J Pharm Biopharm ; 176: 21-31, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35568255

ABSTRACT

Lung cancer (LC) is a common type of cancer, which is a leading cause of death around the world. There is an urgency for the development of new drugs that could diagnose the LC in the early stages and in a precise manner. In this direction, the development of nanoparticles radiolabeled with the diagnostic radioisotopes represent an important advance in the field of cancer imaging. In this study were developed PLA/PVA/Atezolizumab nanoparticles which were radiolabeled with 99mTc (Technetium-99m). The radiolabeled nanoparticles were evaluated in both: in-vitro (L-929 and A-549) as in-vivo (mice). The results showed no cytotoxicity effect in the healthy cells (L-929) and cytotoxicity effect in the tumor cells (A-549). The biodistribution assay demonstrated that 99mTc-PLA/PVA/Atezolizumab could reach the tumor site 14-folds higher than the nonparticulate atezolizumab. In conclusion, 99mTc-PLA/PVA/Atezolizumab nanoparticles showed to be a new drug which is able to precisely image the lung tumor, and it must be considered for clinical trials.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Nanoparticles , Animals , Antibodies, Monoclonal, Humanized , Carcinoma, Non-Small-Cell Lung/diagnostic imaging , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/drug therapy , Mice , Polyesters , Radiopharmaceuticals , Technetium/pharmacology , Tissue Distribution
12.
EJNMMI Radiopharm Chem ; 7(1): 8, 2022 Apr 25.
Article in English | MEDLINE | ID: mdl-35467307

ABSTRACT

BACKGROUND: Recent advances in nanotechnology have offered new hope for cancer detection, prevention, and treatment. Nanomedicine, a term for the application of nanotechnology in medical and health fields, uses nanoparticles for several applications such as imaging, diagnostic, targeted cancer therapy, drug and gene delivery, tissue engineering, and theranostics. RESULTS: Here, we overview the current state-of-the-art of radiolabeled nanoparticles for molecular imaging and radionuclide therapy. Nanostructured radiopharmaceuticals of technetium-99m, copper-64, lutetium-177, and radium-223 are discussed within the scope of this review article. CONCLUSION: Nanoradiopharmaceuticals may lead to better development of theranostics inspired by ingenious delivery and imaging systems. Cancer nano-theranostics have the potential to lead the way to more specific and individualized cancer treatment.

13.
Nanomaterials (Basel) ; 12(2)2022 Jan 13.
Article in English | MEDLINE | ID: mdl-35055267

ABSTRACT

Imatinib (IMT) is a tyrosine kinase enzyme inhibitor and extensively used for the treatment of gastrointestinal stromal tumors (GISTs). A nanostructured lipid carrier system (NLCS) containing IMT was developed by using emulsification-sonication methods. The characterization of the developed formulation was performed in terms of its particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, loading capacity, sterility, syringeability, stability, in vitro release kinetics with mathematical models, cellular uptake studies with flow cytometry, fluorescence microscopy and cytotoxicity for CRL-1739 cells. The particle size, PDI, loading capacity and zeta potential of selected NLCS (F16-IMT) were found to be 96.63 ± 1.87 nm, 0.27 ± 0.15, 96.49 ± 1.46% and -32.7 ± 2.48 mV, respectively. F16-IMT was found to be stable, thermodynamic, sterile and syringeable through an 18 gauze needle. The formulation revealed a Korsmeyer-Peppas drug release model of 53% at 8 h, above 90% of cell viability, 23.61 µM of IC50 and induction of apoptosis in CRL-1739 cell lines. In the future, F16-IMT can be employed to treat GISTs. A small amount of IMT loaded into the NLCSs will be better than IMT alone for therapy for GISTs. Consequently, F16-IMT could prove to be useful for effective GIST treatment.

14.
ACS Omega ; 7(51): 47956-47966, 2022 Dec 27.
Article in English | MEDLINE | ID: mdl-36591122

ABSTRACT

The necessity of new drugs for lung cancer therapy and imaging is increasing each day. The development of new drugs that are capable of reaching the tumor with specificity and selectivity is required. In this direction, the design of nanoparticles for tumor therapy represents an important alternative. The aim of this study was to develop, characterize, and evaluate target-specific atezolizumab-conjugated poly(lactic acid)/poly(vinyl alcohol) (PLA/PVA) nanoparticles as pharmaceutical fragment candidates for new radiopharmaceuticals. For this purpose, PLA/PVA nanoparticle formulations were prepared by the double emulsification/solvent evaporation method with a high-speed homogenizer. A special focus was oriented to the selection of a suitable method for modification of the nanoparticle surface with a monoclonal antibody. For this purpose, atezolizumab was bound to the nanoparticles during the preparation by solvent evaporation or either by adsorption or covalent binding. PLA/PVA/atezolizumab nanoparticles are characterized by dynamic light scattering, Raman spectroscopy, scanning electron microscopy, and atomic force microscopy. An in vitro assay was performed to evaluate the antibody binding efficiency, stability, and cytotoxicity [A549 (lung cancer cell) and L929 (healthy fibroblast cell)]. The results showed that a spherical nanoparticle with a size of 230.6 ± 1.768 nm and a ζ potential of -2.23 ± 0.55 mV was produced. Raman spectroscopy demonstrated that the monoclonal antibody was entrapped in the nanoparticle. The high antibody binding efficiency (80.58%) demonstrated the efficacy of the nanosystem. The cytotoxic assay demonstrated the safety of the nanoparticle in L929 and the effect on A549. In conclusion, PLA/PVA/atezolizumab nanoparticles can be used as drug delivery systems for lung cancer diagnosis and therapy.

15.
Drug Deliv ; 27(1): 1695-1703, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33263456

ABSTRACT

The aim of current study is to develop new nanostructured lipid carrier systems (NLCSs) containing imatinib mesylate (IMT) and evaluate their targeting efficiency on NIH-3T3 as fibroblast cells and CRL-1739 as gastric adenocarcinoma cells with radiolabeled formulations. Three formulations (F1-IMT, F2-IMT and F3-IMT) were prepared and radiolabeled with 1 mCi/0.1 mL of [99mTc]Tc. The effect of reducing and antioxidant agents on radiolabeling process was evaluated and radiochemical purity of formulations was performed by radio thin-layer radiochromatography (RTLC). The results demonstrated that the radiochemical purity was found to be above 90% for [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT, while radiochemical purity of [99mTc]Tc-F3-IMT was found to be 85.61 ± 2.24%. Also, [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT have better stability in cell medium and saline than [99mTc]Tc-F3-IMT. Targeting efficiency of [99mTc]Tc-F1-IMT and [99mTc]Tc-F2-IMT comparatively evaluated by cell binding studies with [99mTc]NaTcO4 on NIH-3T3 and CRL-1739 cells. The cell binding capacity and targeting/non-targeting cell uptake ratio of these two formulations was found to be higher than [99mTc]NaTcO4 in CRL-1739. It is thought that the knowledge achieved in this study would contribute to using [99mTc]Tc-F1-IMT and [99mTc]Tc F2-IMT as an diagnosis and treatment agents.


Subject(s)
Antineoplastic Agents/administration & dosage , Drug Carriers/chemistry , Imatinib Mesylate/administration & dosage , Lipids/chemistry , Nanostructures , 3T3 Cells , Animals , Antineoplastic Agents/metabolism , Cell Line, Tumor , Cell Survival/drug effects , Drug Compounding , Humans , Imatinib Mesylate/metabolism , Isotope Labeling , Mice , Radiopharmaceuticals , Technetium
16.
J Labelled Comp Radiopharm ; 62(13): 874-884, 2019 11.
Article in English | MEDLINE | ID: mdl-31495966

ABSTRACT

The clinical impact and accessibility of 99m Tc tracers for cancer diagnosis would be greatly enhanced by the availability of a new, simple, and easy labeling process and radiopharmaceuticals. 5-Fluorouracil is an antitumor drug, which has played an important role for the treatment of breast carcinoma. In the present study, a new derivative of 5-Fluorouracil was synthesized as (1-[{1'-(1''-deoxy-2'',3'':4'',5''-di-O-isopropylidene-ß-D-fructopyranose-1''-yl)-1'H-1',2', 3'-triazol-4'-yl}methyl]-5-fluorouracil) (E) and radiolabeled with 99m Tc. It was analyzed by radio thin layer chromatography for quality control and stability. The radiolabeled complex was subjected to in vitro cell-binding studies to determine healthy and cancer cell affinity using HaCaT and MCF-7 cells, respectively. In addition, in vitro cytotoxicity studies of compound E were performed with HaCaT and MCF-5 cells. The radiochemical purity of the [99m Tc]TcE was found to be higher than 90% at room temperature up to 6 hours. The radiolabeled complex showed higher specific binding to MCF-7 cells than HaCaT cells. IC50 values of E were found 31.5 ± 3.4 µM and 20.7 ± 2.77 µM for MCF-7 and HaCaT cells, respectively. The results demonstrated the potential of a new radiolabeled E with 99m Tc has selective for breast cancer cells.


Subject(s)
Fluorouracil/chemistry , Fluorouracil/metabolism , Fluorouracil/toxicity , Humans , Hydrogen-Ion Concentration , Isotope Labeling , MCF-7 Cells , Radiochemistry , Technetium/chemistry
17.
Artif Cells Nanomed Biotechnol ; 46(sup3): S725-S733, 2018.
Article in English | MEDLINE | ID: mdl-30449175

ABSTRACT

Breast cancer is women's most common type of cancer, with a global rate of over 522,000 deaths per year. One of the main problems related to breast cancer relies in the early detection, as the specialized treatment. In this direction was developed, characterized and tested in vivo a smart delivery system, based on radiolabelled magnetic core mesoporous silica doped with trastuzumab as intralesional nanodrug for breast cancer imaging and possible therapy. The results showed that nanoparticles had a size of 58.9 ± 8.1 nm, with specific surface area of 872 m2/g and pore volume of 0.85 cm3/g with a pore diameter of 3.15 nm. The magnetic core mesoporous silica was efficiently labelled with 99mTc (97.5% ±0.8) and doped >98%. The cytotoxicity assay, demonstrated they are safe to use. The data were corroborated with the IC50 result of: 829.6 µg ± 43.2. The biodistribution showed an uptake by the tumour of 7.5% (systemic via) and 97.37% (intralesional) with less than 3% of these nanoparticles absorbed by healthy tissues. In a period 6-h post-injection, no barrier delimited by the tumour was crossed, corroborating the use as intralesional nanodrug.


Subject(s)
Drug Carriers , Nanoparticles , Silicon Dioxide , Trastuzumab , Triple Negative Breast Neoplasms , Animals , Cell Line, Tumor , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Female , Humans , MCF-7 Cells , Mice , Mice, Inbred BALB C , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Particle Size , Silicon Dioxide/chemistry , Silicon Dioxide/pharmacokinetics , Tissue Distribution , Trastuzumab/chemistry , Trastuzumab/pharmacokinetics , Trastuzumab/pharmacology , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Xenograft Model Antitumor Assays
18.
Curr Drug Deliv ; 15(3): 342-350, 2018.
Article in English | MEDLINE | ID: mdl-28606033

ABSTRACT

BACKGROUND: Alendronate sodium (ALD) is used orally but it is poorly absorbed from the gastrointestinal (GI) tract. For this reason, microemulsion system was chosen to evaluate ALD from the GI tract after oral delivery. OBJECTIVE: This study was aimed to prepare water-in-oil (w/o) microemulsion formulation of ALD and evaluate the permeability of ALD microemulsion from Caco-2 cell lines with radioactive and nonradioactive studies. METHOD: The ALD microemulsion was developed by using pseudo-ternary phase diagram and composed of Soybean oil, Colliphor EL, Tween 80, Transcutol and distilled water. The prepared ALD microemulsion was characterized by physical appearance, droplet size, viscosity, pH, electrical conductivity and refractive index. The stability of the formulation was investigated for 6 months at 25±2°C/60±5% of relative humidity (RH) as well as at 40±2°C/75±5% RH. After that 1 mg of ALD was radiolabeled with 99mTc and added to microemulsion. The permeability studies were performed with both 99mTc-ALD microemulsion and ALD microemulsion. RESULTS: The experimental results suggested that ALD microemulsion presented adequate stability with droplet size varying from 37.8±0.9 to 39.9±1.2 nm during incubation time. In addition, ALD microemulsion was radiolabeled with high labeling efficiency (>95%). In a non-radioactive study, ALD permeability was found to be 45 µg.mL-1 and microemulsion has high permeability percentage when compared to another study. CONCLUSION: The novel w/o microemulsion formulation has been developed for oral delivery of ALD. Based on the results, permeability of ALD could be significantly improved by the microemulsion formulation. In addition, 99mTc-ALD microemulsion in capsule can be used for bone disease treatment and diagnosis.


Subject(s)
Alendronate/administration & dosage , Bone Density Conservation Agents/administration & dosage , Alendronate/chemistry , Alendronate/pharmacology , Bone Density Conservation Agents/chemistry , Bone Density Conservation Agents/pharmacology , Caco-2 Cells , Emulsions , Excipients/chemistry , Humans , Permeability , Solubility , Surface-Active Agents/chemistry , Technetium
19.
Appl Radiat Isot ; 118: 338-342, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27756051

ABSTRACT

The sentinel lymph node (SLN) is defined as the first regional lymph node to receive lymphatic drainage from a malignant tumor. Therefore, this node is a "sentinel" for second metastatic lymph node stations and for labeling regional tumor spread. For SLN detection, many surgeons preferred a combination of a preoperative injection of radiolabeled colloid and the intraoperative injection of blue dye. Under this combination protocol, nodes are considered to be "sentinel nodes" if they are radioactive and blue. The aim of this study is to develop a new single agent that combines both detection methods. For this purpose Isosulfan Blue (ISB) was radiolabeled by 99mTc with high labeling yield and stability. In vivo gamma scintigraphy studies were performed with rats. According to the scintigraphic studies, 99mTc-ISB shows rapid and high accumulation in both axillary (ALN) and popliteal lymph node (PLN). After the imaging study, extremity was opened and nodes were scanned for the radioactivity. According to performed study the lymph nodes were clearly seen to become blue and carried compound was sufficient to allow identification with a gamma probe. In conclusion, 99mTc-ISB has the potential to facilitate lymphatic mapping and subsequent sentinel node biopsy for solid malignancies such as breast cancer and melanoma.


Subject(s)
Lymph Nodes/cytology , Lymph Nodes/diagnostic imaging , Lymphoscintigraphy/methods , Rosaniline Dyes/chemistry , Technetium/chemistry , Animals , Coloring Agents/chemistry , Isotope Labeling , Radiopharmaceuticals/chemical synthesis , Rats , Rats, Wistar , Reproducibility of Results , Sensitivity and Specificity
20.
Drug Deliv ; 23(8): 3055-3062, 2016 Oct.
Article in English | MEDLINE | ID: mdl-26923781

ABSTRACT

BACKGROUND: Aprotinin is a monomeric globular polypeptide, which derived from bovine lung tissue and theoretically attractive molecule in ameliorating the effects of acute pancreatitis. Acute pancreatitis is an inflammatory condition of the pancreas that is painful and at times deadly. Over the following two decades Aprotinin therapeutic potential on pancreatitis is proven experimentally, its clinical therapeutic success is limited due to low targeting to pancreas. OBJECTIVE: The aim of this study was to evaluate the biodistribution of Technetium-99m (99mTc)-Aprotinin solution (99mTc-Aprotinin-S) and 99mTc-Aprotinin loaded microemulsion, which was prepared for the aim of treatment for acute pancreatitis. METHOD: Aprotinin was radiolabeled with 99mTc. Radiochemical purity was determined with radioactive thin layer chromatography studies. 99mTc-Aprotinin-S and 99mTc-Aprotinin loaded microemulsion (99mTc-Aprotinin-M) was administered to acute edematous, severe necrotizing pancreatitis and air pouch model induced rats. Tissue distribution of Aprotinin was investigated with gamma scintigraphy and biodistribution studies. RESULTS: Aprotinin was radiolabeled by 99mTc with high radiochemical purity (95.430 ± 0.946%). The complex was found to be stable at room temperature up to 6 h. Animal studies have shown that similar to that of other small proteins Aprotinin is accumulated primarily in the kidney. The scintigraphy and biodistribution studies showed that, while i.v. administration of 99mTc-Aprotinin-S distributed mostly in kidneys and bladder, 99mTc-Aprotinin-M, with droplet size of 64.550 ± 3.217 nm, has high uptake in liver, spleen and pancreas. CONCLUSION: This might be concluding that microemulsions may be suggested as promising formulations for selectively targeting Aprotinin to pancreas inflammation.


Subject(s)
Aprotinin/metabolism , Emulsions/metabolism , Pancreatitis/metabolism , Radiopharmaceuticals/metabolism , Technetium/metabolism , Animals , Chemistry, Pharmaceutical/methods , Disease Models, Animal , Male , Particle Size , Radionuclide Imaging/methods , Rats , Rats, Wistar , Tissue Distribution
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