It has been estimated that every year, millions of people are affected by neurodegenerative disorders, which complicate their lives and their caregivers’ lives. To date, there has not been an approved pharmacological approach to provide the complete treatment of neurodegenerative disorders. The only available drugs may only relieve the symptoms or slow down the progression of the disease. The absence of any treatment is quite rational given that neurodegeneration occurs by the progressive loss of the function or structure of the nerve cells of the brain or the peripheral nervous system, which eventually leads to their death either by apoptosis or necrotic cell death. According to a recent study, even though adult brain cells are injured, they can revert to an embryonic state, which may help to restore their function. These interesting findings might open a new path for the development of more efficient therapeutic strategies to combat devastating neurodegenerative disorders. Gene and protein therapies have emerged as a rapidly growing field for various disorders, especially neurodegenerative diseases. Despite these promising therapies, the complete treatment of neurodegenerative disorders has not yet been achieved. Therefore, the aim of this review is to address the most up-to-date data for neurodegenerative diseases, but most importantly, to summarize the available delivery systems incorporating proteins, peptides, and genes that can potentially target such diseases and pass into the blood–brain barrier. The authors highlight the advancements, at present, on delivery based on the carrier, i.e., lipid, polymeric, and inorganic, as well as the recent studies on radiopharmaceutical theranostics.
Radiolabeled trastuzumab (TRZ) loaded solid lipid nanoparticles (SLNs) were prepared by high shear homogenization and sonication techniques. The apoptosis mechanism of TRZ-SLNs was studied only with the MCF-7 cell line, while the cytotoxicity and cell binding capacity were investigated using breast cancer cells (MCF-7 and MDA-MB-231) and the human keratinocyte cell line (HaCaT). The particle sizes of TRZ-SLNs were found to be below 100 nm, and they possessed a negative charge. The high radiolabeling efficiency and good radiolabeling stability in saline and a cell culture medium were obtained in the results of radiolabeling studies. According to the in vitro studies, TRZ-SLNs were found to be biocompatible, and they effectively induced apoptosis in MCF-7 cells. After the parenteral injection of TRZ-SLNs into rats, a sustained release profile in blood circulation was achieved compared with free drug solution by the evaluation of pharmacokinetic parameters. As a conclusion, the study reveals that Technetium-99m (99mTc radiolabeled) TRZ loaded SLN formulations could be promising theranostic agents based on their characterization profiles, in vitro cellular uptake and apoptosis induction capacity, and in vivo pharmacokinetic profiles.
29 October 2020 in Anadolu Kliniği Tıp Bilimleri Dergisi
Yaşamımızın her alanında güneş ışınlarından, soluduğumuz havaya kadar birçok madde nedeniyle radyasyona maruz kaldığımızdan, radyasyonun insan sağlığı üzerindeki etkileri her zaman merak konusu olmuştur. X-ışınlarının keşfiyle başlayan süreçte, özellikle Çernobil Kazası gibi reaktör kazaları ve Hiroşima ve Nagazaki’ye atılan atom bombaları ile radyasyonun etkileri üzerine araştırmalar artmıştır. Yapılan gözlemler sonucunda, maruz kalınan radyasyonun türü, dozu ve maruziyet süresinin sağlığımızı etkileyen ve önemli etkenler olduğu tespit edilmiş ve iyonize radyasyonun, non-iyonize radyasyona kıyasla daha ciddi etkilere sebep olduğu kanıtlanmıştır. İyonize radyasyonun kanser oluşumuna neden olması insanlar için risk faktörü oluştururken, non-iyonize radyasyonun ise uzun dönem çalışmalar sonucu kanıtlanmış etkileri mevcut değildir. Bu derlemede radyasyonun yaşantımızdaki etkileri üzerinde durulmuştur.
Cancer is still a global health problem. Among cancer types, breast cancer is the most frequently diagnosed one, and it causes a high mortality rate if not diagnosed in the early stages. In our study, imatinib encapsulated, nanosized, neutral/cationic liposome formulations were prepared as theranostic agents for breast cancer. After the characterization studies in which all liposomes exhibited proper profile owing to their particle size between 133 and 250 nm, polydispersity index values lower than 0.4, neutral and cationic zeta potential values, and high drug encapsulation efficiency, controlled drug release behaviors with zero‐order kinetic were obtained. The higher than 90% radiolabeling efficiency values were obtained thanks to the determination of optimum radiolabeling condition (80°C temperature, 5 mCi radioactivity, and 10 min incubation period). According to the resazurin assay evaluating the cytotoxic profile of liposomes on MCF7 cells, neutral empty liposome was found as biocompatible, while both cationic liposomes (empty and drug‐loaded ones) exhibited high nonspecific cytotoxicity at even low drug concentration due to the existence of stearyl amine in the formulations. However, dose‐dependent cytotoxic effect and the highest cellular binding capacity were obtained by imatinib loaded neutral liposomes. In conclusion, 68Ga‐radiolabeled, imatinib‐loaded, neutral, nanosized liposome formulation is the most promising one as a theranostic agent among all formulations.
11 May 2023 in Turkish Journal of Pharmaceutical Sciences
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 mu g.mL-1 IBD, 20 mu g 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.
Targeted radiopharmaceuticals offer promising approaches for cancer diagnosis and therapy. This study developed freeze-dried kit formulations of 177 Lu-Imatinib (IMT) and evaluated their potential efficacy through in vitro studies. Four formulations (F1–F4) containing IMT and chelating agents were prepared and characterized via Fourier transform infrared (FTIR), ultraviolet spectrum (UV), and thermogravimetric analysis (TGA) to confirm complex formation. Biocompatibility was assessed in NIH-3T3 cells using the MTT assay. Radiolabeling with 177 Lu was optimized by varying pH, incubation time, and reactant ratios. Radiochemical purity and stability were analyzed over 7 days using HPLC. Binding affinity and cytotoxicity were evaluated in MCF-7 and NIH-3T3 cells. Spectroscopic analyses confirm successful complex formation. All formulations exhibited >90 % viability in NIH-3T3 cells. Optimal radiolabeling conditions (45 mg IMT-chelator, pH 5, 60 min incubation) yielded >90 % efficiency, with stable radiolabeling for 7 days. The 177 Lu-IMT-DOTA (F3) formulation showed significantly higher binding and cytotoxic effects in MCF-7 cells compared to controls. The 177 Lu-IMT-DOTA (F3) kit demonstrates high radiolabeling efficiency, stability, and selective in vitro cytotoxicity toward breast cancer cells, supporting its potential as a targeted radiopharmaceutical.