Radiolabelled FGF-2 for Imaging Activated Fibroblasts in the Tumor Micro-Environment.

Tumor associated fibroblasts (TAFs) play a key role in tumor growth and metastatization. TAFs overexpress different biomarkers that are usually expressed at low levels in physiological conditions. Among them are the fibroblast growth factor receptors (FGFRs) that bind the fibroblast growth factors (FGFs). In particular, the overexpression of FGFR-2c in tumors has been associated with advanced clinical stages and increased metastatization. Here, we developed a non-invasive tool to evaluate, in vivo, the expression of FGFR-2c in metastatic cancer. This is based on 99mTc-labelled FGF-2. METHODS: 99mTc-FGF-2 was tested in vitro and in vivo in mice bearing allografts of sarcoma cells. Images of 99mTc-FGF-2 were acquired using a new portable high-resolution ultra-sensitive gamma camera for small animal imaging. RESULTS: FGF-2 was labeled with high specific activity but low labelling efficiency, thus requiring post-labeling purification by gel-filtration chromatography. In vitro binding to 2C human keratinocytes showed a Kd of 3.36 × 10-9 M. In mice bearing J774A.1 cell allografts, we observed high and rapid tumor uptake of 99mTc-FGF-2 with a high Tumor/Blood ratio at 24 h post-injection (26.1 %ID/g and 12.9 %ID) with low kidney activity and moderate liver activity. CONCLUSIONS: we labeled FGF-2 with 99mTc and showed nanomolar Kd in vitro with human keratinocytes expressing FGF-2 receptors. In mice, 99mTc-FGF-2 rapidly and efficiently accumulated in tumors expressing FGF-2 receptors. This new radiopharmaceutical could be used in humans to image TAFs.

Peritoneal Carcinomatosis of Malignant Gynecological Origin: A Systematic Review of Imaging Assessment.

This systematic review, conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol, aims to comprehensively assess the current state of the art of imaging modalities for the evaluation of peritoneal carcinomatosis arising from malignant gynecological origins, with a focus on ovarian and endometrial cancers. A systematic search of relevant databases was performed, adhering to predetermined inclusion and exclusion criteria. Studies reporting the use of computed tomography (CT), magnetic resonance imaging (MRI), fluorodeoxyglucose (FDG) positron emission tomography (PET), PET/CT, and PET/MRI in the assessment of peritoneal carcinomatosis from gynecological malignancies were included. The review encompasses an overview of selected studies, highlighting the strengths and limitations of each imaging modality in diagnosing and characterizing peritoneal carcinomatosis. Overall, a wide variability in the reported accuracy of different imaging techniques emerges from literature, mainly due to the type of the study, technical issues, and patient characteristics. Although a meta-analysis could not be performed due to a scarcity of data, this systematic review provides valuable insights into the several imaging approaches used in peritoneal carcinomatosis of gynecological origin. The findings aim to inform clinical decision making and guide future research endeavors in this critical aspect of gynecological oncology.

Three-Dimensional In Vitro Tumor Spheroid Models for Evaluation of Anticancer Therapy: Recent Updates.

Advanced tissue engineering processes and regenerative medicine provide modern strategies for fabricating 3D spheroids. Several different 3D cancer models are being developed to study a variety of cancers. Three-dimensional spheroids can correctly replicate some features of solid tumors (such as the secretion of soluble mediators, drug resistance mechanisms, gene expression patterns and physiological responses) better than 2D cell cultures or animal models. Tumor spheroids are also helpful for precisely reproducing the three-dimensional organization and microenvironmental factors of tumors. Because of these unique properties, the potential of 3D cell aggregates has been emphasized, and they have been utilized in in vitro models for the detection of novel anticancer drugs. This review discusses applications of 3D spheroid models in nuclear medicine for diagnosis and therapy, immunotherapy, and stem cell and photodynamic therapy and also discusses the establishment of the anticancer activity of nanocarriers.

Methods for Radiolabeling Nanoparticles (Part 3): Therapeutic Use.

Following previously published systematic reviews on the diagnostic use of nanoparticles (NPs), in this manuscript, we report published methods for radiolabeling nanoparticles with therapeutic alpha-emitting, beta-emitting, or Auger's electron-emitting isotopes. After analyzing 234 papers, we found that different methods were used with the same isotope and the same type of nanoparticle. The most common type of nanoparticles used are the PLGA and PAMAM nanoparticles, and the most commonly used therapeutic isotope is 177Lu. Regarding labeling methods, the direct encapsulation of the isotope resulted in the most reliable and reproducible technique. Radiolabeled nanoparticles show promising results in metastatic breast and lung cancer, although this field of research needs more clinical studies, mainly on the comparison of nanoparticles with chemotherapy.

Formulation Development and Evaluation of Pravastatin-Loaded Nanogel for Hyperlipidemia Management.

Hyperlipidemia is a crucial risk factor for the initiation and progression of atherosclerosis, ultimately leading to cardiovascular disease. The nanogel-based nanoplatform has emerged as an extremely promising drug delivery technology. Pravastatin Sodium (PS) is a cholesterol-lowering drug used to treat hyperlipidemia. This study aimed to fabricate Pravastatin-loaded nanogel for evaluation of its effect in hyperlipidemia treatment. Pravastatin-loaded chitosan nanoparticles (PS-CS-NPs) were prepared by the ionic gelation method; then, these prepared NPs were converted to nanogel by adding a specified amount of 5% poloxamer solution. Various parameters, including drug entrapment efficacy, in vitro drug release, and hemolytic activity of the developed and optimized formulation, were evaluated. The in vitro drug release of the nanogel formulation revealed the sustained release (59.63% in 24 h) of the drug. The drug excipients compatibility studies revealed no interaction between the drug and the screened excipients. Higher drug entrapment efficacy was observed. The hemolytic activity showed lesser toxicity in nanoformulation than the pure drug solution. These findings support the prospective use of orally administered pravastatin-loaded nanogel as an effective and safe nano delivery system in hyperlipidemia treatment.

Emerging Treatment Strategies for Diabetes Mellitus and Associated Complications: An Update.

The occurrence of diabetes mellitus (DM) is increasing rapidly at an accelerating rate worldwide. The status of diabetes has changed over the last three generations; whereas before it was deemed a minor disease of older people but currently it is now one of the leading causes of morbidity and mortality among middle-aged and young people. High blood glucose-mediated functional loss, insulin sensitivity, and insulin deficiency lead to chronic disorders such as Type 1 and Type 2 DM. Traditional treatments of DM, such as insulin sensitization and insulin secretion cause undesirable side effects, leading to patient incompliance and lack of treatment. Nanotechnology in diabetes studies has encouraged the development of new modalities for measuring glucose and supplying insulin that hold the potential to improve the quality of life of diabetics. Other therapies, such as ß-cells regeneration and gene therapy, in addition to insulin and oral hypoglycemic drugs, are currently used to control diabetes. The present review highlights the nanocarrier-based drug delivery systems and emerging treatment strategies of DM.

Dendrimers based cancer nanotheranostics: An overview.

Cancer is a known deadliest disease that requires a judicious diagnostic, targeting, and treatment strategy for an early prognosis and selective therapy. The major pitfalls of the conventional approach are non-specificity in targeting, failure to precisely monitor therapy outcome, and cancer progression leading to malignancies. The unique physicochemical properties offered by nanotechnology derived nanocarriers have the potential to radically change the landscape of cancer diagnosis and therapeutic management. An integrative approach of utilizing both diagnostic and therapeutic functionality using a nanocarrier is termed as nanotheranostic. The nanotheranostics platform is designed in such a way that overcomes various biological barriers, efficiently targets the payload to the desired locus, and simultaneously supports planning, monitoring, and verification of treatment delivery to demonstrate an enhanced therapeutic efficacy. Thus, a nanotheranostic platform could potentially assist in drug targeting, image-guided focal therapy, drug release and distribution monitoring, predictionof treatment response, and patient stratification. A class of highly branched nanocarriers known as dendrimers is recognized as an advanced nanotheranostic platform that has the potential to revolutionize the oncology arena by its unique and exciting features. A dendrimer is a well-defined three-dimensional globular chemical architecture with a high level of monodispersity, amenability of precise size control, and surface functionalization. All the dendrimer properties exhibit a reproducible pharmacokinetic behavior that could ensure the desired biodistribution and efficacy. Dendrimers are thus being exploited as a nanotheranostic platform embodying a diverse class of therapeutic, imaging, and targeting moieties for cancer diagnosis and treatment.

Pharmaceutical Aspects of Green Synthesized Silver Nanoparticles: A Boon to Cancer Treatment.

BACKGROUND: Silver nanoparticles (AgNPs) are among the most investigated nanostructures in recent years, which exhibit more challenging and promising qualities in different biomedical applications. The AgNPs synthesized by the green approach provide potential healthcare benefits over chemical approaches, including improvement of tissue restoration, drug delivery, diagnosis, being environmentally friendly, and a boon to cancer treatment. OBJECTIVE: In the current scenario, the development of safe and effective drug delivery systems is the utmost concern of formulation development scientists as well as clinicians. METHODS: Google, Web of Science, and PubMed portals have been searched for potentially relevant literature to get the latest developments and updated information related to different aspects of green synthesized AgNPs along with their biomedical applications, especially in the treatment of different types of cancers. RESULTS: The present review highlights the latest published research regarding the different green approaches for the synthesis of AgNPs, their characterization techniques as well as various biomedical applications, particularly in cancer treatment. In this context, environment-friendly AgNPs are proving themselves as better candidates in terms of size, drug loading and release efficiency, targeting efficiency, minimal drug-associated side effects, pharmacokinetic profiling, and biocompatibility issues. CONCLUSION: With continuous efforts by multidisciplinary team approaches, nanotechnology-based AgNPs will shed new light on diagnostics and therapeutics in various disease treatments. However, the toxicity issues of AgNPs need greater attention as unanticipated toxic effects must be ruled out for their diversified applications.

Orally administered self-emulsifying drug delivery system in disease management: advancement and patents.

Introduction: Oral administration of a drug is the most common, ideal and preferred route of administration. The main problem of oral drug formulations is their low bioavailability arises from poor aqueous solubility of drug. Aqueous solubility of lipophilic drugs can be improved by various techniques like salt formation, complexation, addition of co-solvent etc. but self-emulsifying drug-delivery system (SEDDS) is getting more attention for increasing the solubility of such drugs. The SEDDS is an isotropic mixture of drug, lipids, and emulsifiers, usually with one or more hydrophilic co-solvents/co-emulsifiers. This system is having ability to generate oil-in-water (o/w) emulsions or microemulsions upon gentle agitation followed by dilution with aqueous phase. The SEDDSs are relatively newer, lipid-based technological innovations possessing unparalleled potential in improving oral bioavailability of poorly water-soluble drugs.Areas covered: This review provides updated information regarding the types of SEDDS, their preparation techniques, drug delivery and related recent patents along with marketed formulations.Expert opinion: The SEDDS has been explored for improving bioavailability, rising intra-subject heterogeneity, and increasing solubility. SEDDS offers the benefit of a protective effect against the hostile environment in the gut. The unique fabrication techniques provide specific strategy to overcome the low bioavailability and poor solubility problems.