Albumin Microspheres Research Articles

PH-sensitive adriamycin hydrochloride and oxaliplatin dual-loaded microspheres synergistically enhance local injections effect of hepatocellular carcinoma

Chemotherapy is the primary palliative treatment for advanced hepatocellular carcinoma (HCC). However, the systemic delivery is associated with the drawbacks including a high risk of adverse effects and a low efficacy. Therefore, local injection therapy may be beneficial. Nevertheless, the existing local drug-carrying microspheres(DOBM)have the characteristics of low loading and abrupt release, can not simultaneously load two drugs, and may cause unnecessary toxicity. In this study, we created the dual-loaded bovine serum albumin (BSA) microspheres (also known as DOBM), which were hollow and contained both oxaliplatin (OXA) and Adriamycin hydrochloride (DOX). In addition, this pH-sensitive drug delivery method exhibited a high drug loading capacity and was promising in breaking through biological barriers, making it a viable option for the treatment of HCC through local implantation. Based on physiochemical evaluation of BSA microspheres, they had a porous structure which was close to the surface. Adriamycin and oxaliplatin were successfully added to the surface of BSA microspheres. According to in vitro experimental results, the growth of human HCC (HCC-LM3 and PLC/PRF/5) cell lines was significantly inhibited by DOBM. Furthermore, in the subcutaneous PLC/PRF/5 HCC model, DOBM played an essential role in tumor development and change in the tumor microenvironment.

Evaluation of the possibilities of using albumin microspheres for radioaerosol study of the deposition of inhaled substances and mucociliary clearance

The need to study and evaluate the leading protective mechanisms of the respiratory system remains one of the key, but unresolved problems of modern medicine, concerning both radiation hygiene and toxicology, and pulmonology. The model of the respiratory tract presented by the ICRP only partially addresses them, significantly limiting the feasibility and possibilities of its use. The solution of this problem undoubtedly contributes to the improvement of methods of prevention and treatment from the effects of incorporative radionuclides entering by inhalation, as well as methods for diagnosing and treating respiratory diseases aimed at the earliest stages of their pathogenesis, given that the processes of deposition of inhaled substances and lung clearance directly depend both therapeutic and pathogenic effects. This is especially relevant when there is a danger of contamination with radioactive waste, when there is an urgent need to deal with highly pathogenic influence and its consequences. The most informative method for studying the processes of deposition inhalant and mucociliary clearance is radioaerosol. However, due to the circumstances, there are no radiopharmaceuticals that could be used for such a study since the 2000s, which prompted us to carry out this work. At the same time, albumin microspheres labeled with 99mTc are considered potentially suitable, but not studied radiopharmaceuticals in this regard. The aim of the work was to study the aerodynamic properties of albumin microspheres and evaluate the possibilities of their use for radioaerosol study of the processes of deposition of inhaled substances and mucociliary clearance. The aerodynamic properties of albumin micro[1]spheres were studied using optical and scanning electron microscopy by studying their dry dispersion, initial and obtained from its suspension in distilled water, generated by an ultrasonic inhaler according to the developed technology. The results indicated that the dispersible particles were characterized by sphericity, clear boundary differentiation and a relatively homogeneous distribution of particles with a relatively narrow size range (spread 1-2.5 µm) and little conglomeration, as well as a smooth surface. Conclusion. The investigated albumin microspheres are suitable for radioaerosol study of the processes of deposition of inhaled substances and mucociliary clearance.

Результаты клинического исследования безопасности радиофармацевтического лекарственного препарата с Re-188 при проведении внутриартериальной радиоэмболизации

About 10% of all malignant liver neoplasms are inoperable both in Russia and worldwide. The most effective treatment of these patients is chemo- and radioembolization. For the treatment of inoperable primary and secondary liver cancer using intra-arterial radioembolization, a Russian radiopharmaceutical (RF) has been developed based on albumin microspheres with a diameter of 20-40 microns, labeled with the radioisotope rhenium-188 (RP “Gepatoren-MRRC”). Preclinical studies and phase 1 clinical studies were conducted. The aim of this work was the investigation of the safety of RP “Hepatoren-MRRC” during radioembolization in patients with inoperable primary and secondary liver cancer and selection of safe and maximum tolerated dose of the radiopharmaceutical. Intra-arterial radioembolization with Hepatoren-MRRC, 3-6 GBq, was given to 20 patients with the following diagnoses: primary liver cancer (C22.0, C22.1), metastatic liver cancer (C19.0, C22.1, C18.7, C18.0, C20.0). All patients underwent whole-body scintigraphy and SPECT at 2, 24, 48, and 72 h after procedure. Radiometry of patients' urine, which was taken within 48 h after radioembolization, was also performed. The patients were followed up for 3 months. Urinary excretion of RP was an average 23% [12%-40%] during 48 h after treatment. No accumulation of free 188Re in the thyroid gland was observed. A small (5.5%-13.2%) pulmonary shunt was observed in all patients. The diagnostic SPECT/CT image with RP «99mTc-MAA» in all patients coincided with the post-therapy SPECT/CT image with RP “Hepatoren-MRRC”. Internal radiation doses delivered to tumor ranged from 9.2 to 68.5 Gy. The values of individual radiation doses delivered to critical organs were many times less than the generally accepted dose limits for radiotherapy. Grade 1 of haematological toxicity was observed in 15 (75%) patients, grade 2 – in 3 (15%) patients, grade 3 – in 2 (10%) patients. Grade 2 of hepatological toxicity was observed in all patients. Good tolerability of RP was observed in 10 (50%) patients, satisfactory tolerability – in 7 (35%) patients and unsatisfactory tolerability – in 3 (15%) patients. No significant complications were identified during the follow-up period. One patient died 2 months after radioembolization by reason of progression of the main disease. According to the results of the Phase 1 of clinical trial we can conclude about safety and tolerability of RP “Hepatoren-MRRC” of 3-6 GBq for radioembolization in patients with inoperable liver cancer.

Radioembolization of the liver by <sup>188</sup>Re albumin microspheres 20–40 μm (“HEPATOREN”): results of the first phase of the study

Radioembolization of the liver by <sup>188</sup>Re albumin microspheres 20–40 μm (“HEPATOREN”): results of the first phase of the study

Персонализированная дозиметрия внутреннего облучения опухолевых образований и органов риска пациентов: разработка и реализация методического базиса для дозиметрического обеспечения клинических исследований терапевтических радиофармпрепаратов

The cluster of calculational and instrumental methods for estimation of personalized internal radiation doses to foci and organs at risk among patients undergoing to therapy by radiopharmaceuticals has been developed. The developed set of methods was used for dosimetrical support of clinical trials of therapeutic radiopharmaceuticals: a) Lu-177-DOTA-PSMA (or "Lutaprost") targeted for radioligand therapy of metastatic castrate-resistant prostate cancer; b) Re-188 albumin microspheres 5-10 μm (or "Artroren") targeted for radiosynovectomy in the local treatment of chronic inflammatory diseases of the joints and c) 188Re albumin microspheres 20-40 μm (or "Gepatoren") targeted for intra-arterial radionuclide embolization in the treatment of inoperable liver cancer. The results of estimations absolute activities of radiopharmaceuticals and their dynamics during SPECT/CT scanning of radiopharmaceuticals in the body of patients were verified by measurements using physical phantoms of humans with different body weights and various standard activities of radionuclides distributed inside the phantoms. The developed cluster of programs (for calculating the absorbed fraction of energy in biostructures), relevant databases and instrumental methods were used as the basis for estimations personalized internal radiation doses in foci and organs at risk among patients included in clinical trials of the studied radiopharmaceuticals. Individual internal radiation doses in foci among 39 patients, included in the first phase of clinical trials of the three studied radiopharmaceuticals, were estimated. The analysis of the distribution of estimated doses shows that absorbed doses in foci are very differing not only in different patients, but also in different foci in the same patient. Irradiation doses in foci increase with an increasing in the administered activities of radiopharmaceuticals and, depending on the volume of foci, are within the following ranges: 1) in a case of “Lutaprost” – from 1.4 to 32 Gy (planned administered activity – 5 GBq), from 5.1 to 59 Gy (planned activity – 7.5 GBq), from 13 to 94 Gy (planned activity – 10 GBq); 2) in a case of "Arthroren" – from 17.5 to 74 Gy (planned administered activities – from 0.37 to 0.925 GBq); 3) in a case of “Gepatoren” – from 10.7 to 43 Gy (planned administered activities – from 1 to 3 GBq). Individual absorbed doses in organs at risk were estimated as well. Dose values in organs at risk also vary greatly between different patients and between different critical organs. These doses ranged from 0.01 to 7.4 Gy (39 patients), which is many times less than “commonly applied dose constraints” in radiotherapy.

Preparation and Study of Folate Modified Albumin Targeting Microspheres.

In this study, folate modified bovine serum albumin was successfully synthesized, while preparation of Nintedanib albumin microspheres (ND-FSA NPs) as a carrier was carried out via electrospinning technology. Folate modified albumin was used to enhance the targeting potential of the prepared microspheres. The prepared microspheres had spherical appearance and smooth outer surface. The diameters of microspheres (764.68 ± 88.46 nm) and zeta potential (- 18.38 ± 0.41 mV) were acceptable. The prepared ND-FSA NPs demonstrated a good degree of modification, wherein the modification rate was 28.1%. In vitro release was significantly increased in three different media (double deionized water-DDW, HCl-pH 1.2, and phosphate buffered solution containing 0.5% Tween 80). It is worth noting that incorporation of Nintedanib into folic acid modified albumin microspheres resulted in an enhanced uptake of the drug into MCF-7 breast cancer cells coupled with higher inhibition rate. Altogether, incorporation of Nintedanib into folate modified albumin microspheres is a new approach to improve water solubility and targeting effect of the drug.

Preparation, physicochemical, and antibacterial properties of bovine serum albumin microspheres loaded with sodium nitrite

In this study, NaNO2-embedded bovine serum albumin microspheres (BSAMs) were prepared by oil-in-water emulsification method, which was covalently cross-linked with transglutaminase (TGase). Moreover, the physicochemical properties and antibacterial effect of BSAMs on Escherichia coli, Staphylococcus aureus, Pseudomonas, and beef and pork jerky were also analyzed. The particle size of BSAMs was about 0.5–2.5 μm observed by scanning electron microscopy. Almost all NaNO2 was encapsulated inside BSAMs, and there was no NaNO2 attaching on the surface of BSAMs. The encapsulation rate of NaNO2 first increased from 0 to 20 U/g TGase and then decreased from 20 to 40 U/g TGase; likewise, the release of NO first increased with the increase of TGase (0–20 U/g) and it decreased when the TGase concentration was 30 and 40 U/g. Based the results of minimal inhibitory concentration and minimal bactericidal concentration, E. coli and Pseudomonas were more sensitive to BSAMs than S. aureus. In addition, the slow release of NO from BSAMs could significantly inhibit the growth of bacteria on the surface of beef and pork jerky in a weak acidic environment compared with NaNO2 used directly, so as to achieve long-term antibacterial effect and prolong the shelf life of meat products.

Albumin Microspheres as “Trans-Ferry-Beads” for Easy Cell Passaging in Cell Culture Technology

Protein hydrogels represent ideal materials for advanced cell culture applications, including 3D-cultivation of even fastidious cells. Key properties of fully functional and, at the same time, economically successful cell culture materials are excellent biocompatibility and advanced fabrication processes allowing their easy production even on a large scale based on affordable compounds. Chemical crosslinking of bovine serum albumin (BSA) with N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) in a water-in-oil emulsion with isoparaffinic oil as the continuous phase and sorbitan monooleate as surfactant generates micro-meter-scale spherical particles. They allow a significant simplification of an indispensable and laborious step in traditional cell culture workflows. This cell passaging (or splitting) to fresh culture vessels/flasks conventionally requires harsh trypsinization, which can be omitted by using the “trans-ferry-beads” presented here. When added to different pre-cultivated adherent cell lines, the beads are efficiently boarded by cells as passengers and can be easily transferred afterward for the embarkment of novel flasks. After this procedure, cells are perfectly viable and show normal growth behavior. Thus, the trans-ferry-beads not only may become extremely affordable as a final product but also may generally replace trypsinization in conventional cell culture, thereby opening new routes for the establishment of optimized and resource-efficient workflows in biological and medical cell culture laboratories.

THE HIDING HEPATIC HYDROTHORAX

TOPIC: Lung Pathology TYPE: Fellow Case Reports INTRODUCTION: Hepatic Hydrothorax is excessive accumulation of pleural fluid in patients with decompensated liver cirrhosis without pulmonary or cardiac disease. Radioisotope diagnostic techniques are used to confirm doubtful cases of hepatic hydrothorax. [1] Here we describe an unusual case of pleural chylothorax secondary to hepatic hydrothorax(HH). CASE PRESENTATION: 68 yr-old-female with history of NASH liver cirrhosis, portal hypertension, RCC of the kidney s/p right partial nephrectomy, chronic kidney disease and MGUS presented with shortness of breath and abdominal distention. On examination she had diminished breath sounds and abdominal ascites with fluid thrill. Initial CT chest, abdomen and pelvis showed moderate right pleural effusion with liver cirrhosis and moderate ascites. During the course of her hospitalization, she underwent multiple diagnostic and therapeutic paracentesis and thoracentesis. Analysis of the pleural fluid was consistent with chylothorax, ascitic fluid had elevated triglycerides however was not diagnostic of chylous ascites. Microbiological work up was negative. No malignant cells were identified. She was started on optimal diuretic therapy. A peritoneum shunting study with SPECT/CT using technetium 99m MAA was performed with evidence of hepatic hydrothorax, following which she underwent a Transjugular intrahepatic portosystemic shun (TIPS) procedure. DISCUSSION: Spontaneous chylothorax after liver cirrhosis is a known entity. Triglyceride levels >200 mg/dl in ascitic fluid [2] and >110 mg/dl in pleural fluid is consistent with a chylous effusion. Migration of intraperitoneally infused 99mTc-labeled microspheres of human serum albumin or a sulfur colloid into the pleural cavity confirms the diagnosis of hepatic hydrothorax in unequivocal cases. The rate of isotope movement indicates the size of defects in the diaphragm. Ditah et al provided a systematic review and meta-analysis of a total of 198 patients suffering from HH where TIPS successfully eliminated the symptoms of refractory HH in 73% of cases. [3] CONCLUSIONS: In conclusion patient developed chylothorax from her ascites which was not evident on initial pleural and ascetic analysis. REFERENCE #1: [1] Dmitry Victorovich Garbuzenko, Nikolay Olegovich Arefyev, Hepatic hydrothorax: An update and review of the literature, World J Hepatol 2017 November 8; 9(31): 1197-1204 REFERENCE #2: [2] Chylous Ascites: A Review of Pathogenesis, Diagnosis and Treatment Richa Bhardwaj*1, Haleh Vaziri1, Arun Gautam1, Enrique Ballesteros2, David Karimeddini3 and George Y. Wu1 1 Department of Medicine, Division of Gastroenterology-Hepatology, UCONN Health, Farmington, CT, USA; 2 Department of Pathology and Lab Medicine, UCONN Health, Farmington, CT, USA; 3 Department of Diagnostic Imaging and Therapeutics, UCONN Health, Farmington, CT, USA REFERENCE #3: [3]Ditah IC, Al Bawardy BF, Saberi B, Ditah C, Kamath PS. Transjugular intrahepatic portosystemic stent shunt for medically refractory hepatic hydrothorax: A systematic review and cumulative meta-analysis. World J Hepatol 2015; 7: 1797-1806 [PMID: 26167253 DOI: 10.4254/wjh.v7.i13.1797] DISCLOSURES: No relevant relationships by Bharat Bhandari, source=Web Response No relevant relationships by Saadia Faiz, source=Web Response No relevant relationships by Carlos Jimenez, source=Web Response

Sonochemically Prepared BSA Microspheres as Adsorbents for the Removal of Organic Pollutants from Water.

This work investigates, for the first time, the application of sonochemically prepared bovine serum albumin (BSA) microspheres (BSAMS) as adsorbents of industrial organic pollutant dyes, such as rhodamine B (RhB), rhodamine 6G (Rh6G), and methylene blue (MB). These dyes also serve as model compounds for other organic pollutants such as bisphenol A and 2-nitrophenol. Adsorption kinetics of the dyes by the BSAMS was studied using pseudo-first-order (PFO) and pseudo-second-order (PSO) kinetic models. It was found that RhB follows PFO, with an adsorption capacity, qe,cal, of 7.9 mg/g, which was closer to the experimental adsorption capacity of qe,exp. of 7.6 mg/g. However, MB and Rh6G were controlled by PSO kinetics, with a qe,cal of 5.6 mg/g for MB and 6.6 mg/g for Rh6G, closer to the experimental adsorption capacity of 5.7 and 6.4 mg/g, respectively. The intraparticle diffusion (ID) model applied to the three dyes indicated multi-linearity with ID as the rate-limiting step in the adsorption process. Furthermore, the adsorption equilibria for each of the organic pollutants were studied through various isotherm models such as Langmuir, Freundlich, Temkin, and Halsey, which indicated physical interaction between the BSAMS and the dye pollutants, thus suggesting the applicability of the BSAMS as pollutant adsorbent materials. It was found that the BSAMS can effectively remove RhB, MB, and Rh6G from wastewater with efficiencies of 95.5, 83.3, and 97.9%, respectively.

Dosimetry of radiopharmaceuticals used in adult patients with suspected pulmonary embolism

The absorbed dose of radiopharmaceuticals is estimated in adults with suspected pulmonary embolism explored by ventilation/perfusion studies. For pulmonary ventilation studies 81mKr, 133Xe, 99mTc (Technegas)-aerosol and 99mTc (DTPA)-aerosol are used. For perfusion agents, 99mTc(MAA), 99mTc (MSA) (macroaggregates and albumin microspheres) are used. For the dose calculation, the MIRD methodology and the anthropomorphic representation of the biokinetic organs of Cristy-Eckerman are used. In ventilation/perfusion studies, the lowest dose absorbed by the lungs with suspected embolism is due to 81mKr/ 99mTc (MSA), and the highest dose is due to 99mTc (Technegas)/99mTc (MAA) calculated for activities of 150 MBq for perfusion agents and 40 MBq for ventilation agents.

Исследование Радиационной Безопасности gри Приготовлении 188Re-меченных Микросфер Альбумина lля Лечения Резистентных Синовитов

The article is written about studying of radiation safety of 188Re-labeled microspheres of albumin preparation (hand mode) for treatment of resistant synovitis. The study material was a radiopharmaceutical based on albumin microspheres 5 –10 µm with rhenium-188 for treatment of resistant synovitis. The studying has led to conclusion the number of radiopharmaceutical portions prepared by one operator should not exceed 70 times a year, which will ensure that the main limits of equivalent doses to hands and skin with a reserve factor of 2 (250 μSv/h) are not exceeded. Protective equipment should be used to reduce doses to hands, as the most critical to operator's body part irradiation.

РЕЗУЛЬТАТЫ ДОКЛИНИЧЕСКИХ ИССЛЕДОВАНИЙ БЕЗОПАСНОСТИ РАДИОФАРМПРЕПАРАТА С 90Y ДЛЯ ВНУТРИАРТЕРИАЛЬНОЙ РАДИОЭМБОЛИЗАЦИИ ЗЛОКАЧЕСТВЕННЫХ НОВООБРАЗОВАНИЙ ПЕЧЕНИ

Purpose: Performing a safety study of a radiopharmaceutical drug with yttrium-90 for intra-arterial radioembolization of inoperable patients with primary and metastatic liver cancer.
 Material and methods: The developed radiopharmaceutical is a microspheres of human blood albumin with a diameter of 25-40 microns, modified with diethylenetriaminpentaacetic acid and labeled with 90Y radionuclide. The safety of the radiopharmaceutical was studied by the following indicators: acute toxicity of lyophilized reagents, subchronic toxicity of the radiopharmaceutical on two types of animals, local irritant effect of the radiopharmaceutical therapeutic activity in equivalent terms on laboratory animals, specific toxicity (allergizing effect) of lyophilized reagents for the preparation of a radiopharmaceutical drug. Female and male BALB/C mice, Wistar rats, chinchilla rabbits, and albino Guinea pigs were taken as experimental animals. All animals were obtained from certified laboratory animal nurseries.
 Results: During acute toxicity studies, the maximum safe dose of an inactive drug was determined. In terms of per person, it exceeds the intended dose for clinical use by almost 20 times. The study of the subchronic toxicity of the radiopharmaceutical did not reveal any symptoms of intoxication. The survival rate of the animals during the entire observation period was absolute. Standard behavior and appearance were observed in animals. The dynamics of body weight was positive, and the body temperature of rats and rabbits did not exceed the limits allowed. Samples of the finished dosage form of the drug did not have a local irritant effect. The solution of inactive components of lyophilized reagents for the preparation of a radiopharmaceutical drug did not have an allergenic effect in quantities ten times higher than the doses administered to a person.
 Conclusion: According to the results of preclinical studies, the radiopharmaceutical should be considered safe for use. The results of preclinical studies allow us to recommend the drug for clinical research.

РЕЗУЛЬТАТЫ ДОКЛИНИЧЕСКИХ ИСПЫТАНИЙ ЭФФЕКТИВНОСТИ РАДИОФАРМПРЕПАРАТА «ДТПА-МИКРОСФЕРЫ АЛЬБУМИНА, 90Y»

Purpose: Development of technology for producing a radiopharmaceutical based on 90Y labeled modified human blood albumin microspheres, and the study of the functional suitability of this drug in experimental animals.
 Material and methods: The research team studied the following characteristics of the drug: the distribution and excretion of the drug after its intra-arterial administration; the mechanism of action of the drug in animals with model pathology; therapeutic efficacy of the drug in animals with a liver tumor model.
 The following physicochemical characteristics of the developed radiopharmaceutical were announced: modified with DTPA and labeled 90Y human blood albumin microspheres, particle size 25-40 microns, radiochemical impurities less than 5.0%, 90Sr radionuclide impurities less than 0.002%, the amount of chemical impurities (Na, Al, Ca, Fe, Cu, Zn, Cd, Pb) not more than 10 μg / GBq, volumetric activity up to 150 mCi / ml at the date of preparation. 
 Sprague Dawley female rats were taken as experimental animals (body weight 220-260 g). Studies were conducted on a model pathology - hepatocellular carcinoma, which occurs in 85% of all malignant tumors of the human liver.
 Results: in 2018-2019, nine pilot batches of the radiopharmaceutical product satisfying the declared characteristics were developed. Stable inhibition of the growth of tumor lesions by 7.62% was noted. The quality of life in animals with orthotopic tumor foci of hepatocarcinoma treated was better than in animals not treated. Life expectancy in the group of animals treated with the drug was higher than in the group of animals that did not receive treatment by 7.1%. The distribution of the drug was characterized by pulmonary bypass, not exceeding 9% of the injected activity and minimal forwarding into the circulating blood. The radiopharmaceutical was firmly held at the injection site and remained almost unchanged throughout the study. Binding to the tumor site of the drug was characterized by retention of at least 78% of the introduced activity. 
 Conclusion: Conducted preclinical studies of the pharmacokinetics of the drug show its potential suitability for the treatment of liver cancer by radionuclide embolization. According to the results of preclinical studies of the therapeutic effectiveness of the radiopharmaceutical, it should be considered effective for use.

Formulation and Optimization of Albumin Microspheres for Controlled Delivery of Gene (Research Article)

Formulation and Optimization of Albumin Microspheres for Controlled Delivery of Gene (Research Article)

Биораспределение микросфер альбумина, меченных Re-188, при различных путях введения

Nowadays the radiolabeled microspheres are established tools for radioembolization of primary and metastatic liver cancer. Human serum albumin microspheres (HSA) are unique carriers for selective and controlled radionuclide delivery to malignant tumors. Rhenium-188 (Re-188), which decays with beta particles (2.12 MeV (71.1%) and 1.965 MeV (25.6%) and gamma emission (155 keV (15.1%)) is one of the most available and promising generator-based radionuclide for cancer therapy. The purpose of this work was to study the biodistribution of microspheres based on hu-man serum albumin labeled with Re-188 (Re-188-HSA) in animals after different routes of admin-istration. The size of more than 95% of microspheres was 10-20 μm. The studies were carried out on outbred white mice and inbred C57BL/6 mice with transplanted Lewis adenocarcinoma after intravenous, intramuscular and intratumoral administration. After intravenous injection the high-est amount of Re-188-HSA in organs and tissues was observed: up to 311.3%/g in lungs, up to 74.30%/g in thyroid gland, up to 12.70%/g in liver, up to 0,81%/g in blood. After the intramuscular injection of 188Re-HSA, the concentration of 188Re-HSA in organs and tissues was significantly lower and did not exceed 1%/g, except for thyroid gland (1,10-17.80%/g). After intratumoral injec-tion the amount of Re-188-HSA in tumor varied from 16.7 to 26.8%/g, that was higher as compared with other organs and tissues. Thus, the routes of Re-188-HSA administration significantly affect its behavior in the body. The obtained results can be used to evaluate the Re-188-HSA potential for radionuclide tumor therapy after intravascular or intratumoral administration.

Targeted Drug Delivery to Cancer Stem Cells through Nanotechnological Approaches.

Cancer Stem Cells (CSCs) are responsible for tumor development, invasion and metastasis and resistance to chemotherapy and radiotherapy. Therefore, treatment strategies have turned to targeting CSCs, and utilizing nanotechnological approaches to target CSCs has become increasingly fascinating. Functionalized nanoparticles (NPs), such as metallic NPs, liposomes, polymeric NPs, albumin microspheres and nanomicelles, can easily cross the cytoplasmic membrane and accumulate at their targets to continuously release therapeutic agents in response to the characteristics of the tumor microenvironment. Different kinds of NPs possess different characteristics. Inducing immune responses might be the disadvantage they commonly owned through the summary and analysis of these NPs. For natural polymers, they have many attractive properties, but deficiencies also exist such as poor water-solubility, high viscosity, high permeability, etc. The drug-encapsulated NPs launched in the market and those in the clinical trials exhibit a bright prospect in cancer targeted therapy. In addition, the application of nanodiagnostic techniques, such as nanocantilever and DNA microarray technology and early cancer detection has become an indispensable component in clinical practice to improve in vivo detection and enhance targeting efficiency. This review mainly determines the species and usages of NPs in drug delivery and disease diagnosis, the delivery mechanisms of NPs, the main factors that affect nanomedicine efficiency and toxicity and the further trends in the development of targeted therapy. Nevertheless, more and deeper investigations are still needed to avert potential adverse effects and improve the delivery efficiency to achieve better therapeutic effects.

Development and validation of an HPLC method for determination of rofecoxib in bovine serum albumin microspheres.

A simple and reliable HPLC method was developed and validated for determination of rofecoxib in bovine serum albumin microsphere. The analyses were performed on a C18 column (150 x 4.6 mm, 5 μm particle size) at room temperature with UV detection at 272 nm. The mobile phase was composed of acetonitrile-0.1% o-phosphoric acid solution in water (1:1, v/v) mixture, and flow rate was set to 1 mL/min. The method was validated according to the international guidelines with respect to stability, linearity range, limit of quantitation and detection, precision, accuracy, specificity, and robustness. The detection and quantification limit of the method were 1.0 μg/mL and 2.5 μg/mL, respectively. The method was linear in the range of 2.5–25 μg/mL with excellent determination coefficients (R2 >0.99). Intra-day and inter-day precision (<1.76% RSD) and accuracy (<0.55 % Bias) values of the method also fulfilled the required limits. It was concluded that the developed method was accurate, sensitive, precise, and reproducible according to the evaluation of the validation parameters. The applicability of the method was confirmed for in vitro quantification of rofecoxib in bovine serum albumin microspheres.

Radioguided Surgery, a Cost-Effective Strategy for Treating Solitary Pulmonary Nodules: 20-Year Experience of a Single Center

IntroductionSurgical resection with minimally invasive approach is the gold standard for both definitive diagnosis and treatment of solitary pulmonary nodules (SPNs); however, it can be difficult to pinpoint small, deep, or subsolid nodes without palpating lung parenchyma. The primary endpoint of this study is showing that radioguided surgery is a cost-effective strategy to improve the effectiveness of video-thoracoscopic localization/resection of SPNs/ground-glass opacities (GGOs). Secondary endpoints are analyzing the morbidity of this technique and tips and tricks to better manage this method. MethodsSPN smaller than 20 mm and/or with a distance from the visceral pleura ≥5 mm underwent minimally invasive resection after computed tomography-guided injection of a solution composed of 0.1/0.2 mL of 99Tc-labeled human serum albumin microspheres and 0.1 mL of nonionic contrast. In the operating theater, a collimated probe connected to a gamma ray detector allowed localization of the target area. ResultsBetween 1997 and 2018, a total of 451 patients with SPN/GGO underwent minimally invasive surgery with a radioguided technique at our hospital. The mean SPN diameter was 13 mm (range, 5-20 mm), and the mean distance from the visceral pleura was 15 mm (range, 6-29 mm). The mean time to a localizing nodule was 3 minutes (range, 1-5 minutes). No significant injection-related complications were reported; only 3.3% of patients (15 of 451) developed pneumothorax. Both 30- to 60-day and 90-day mortality were 0%. The rate of postoperative complications was 2.53% (prolonged air leak). The conversion rate to thoracotomy was 1.55% (7 of 451). ConclusionsOur 20-year experience shows that radioguided thoracoscopic surgery is a safe and feasible strategy to treat suspicious SPN/GGO, with a success rate of 98%.

Silver-incorporated hydroxyapatite–albumin microspheres with bactericidal effects

Bacterial adhesion on HA-coated implant is a serious problem that often leads to bone infection such as osteomyelitis on implant sites. Gram-positive bacteria such as Staphylococcus aureus are responsible for such infection-forming biofilm on implant surfaces. Therefore, inclusion of antimicrobial agents especially inorganic ions such as silver has gained vogue due to their strong antibacterial effects. This study reports the fabrication of porous Ag–albumin–HA microspheres by water-in-oil emulsion technique. Varied proportions of porogen with HA ensured enhanced pores in the fabricated microsphere. Further, SEM analysis revealed the presence of microspheres in the range ~ 50–900 μm with interconnected pores ranging between ~ 10 and 50 μm. Antibacterial efficacy of the Ag–HA hybrid disrupting the biofilm was observed. The as-formed microspheres having interconnected pore channels are envisaged to show vascularization as well as fulfilling goals of ideal bone filler ensuring biocompatibility and reducing long-term cytotoxicity at implant site.