Factors affecting response variables with emphasis on drug release and loading for optimization of liposomes.

Drug delivery through Liposomes has shown tremendous potential in terms of the therapeutic application of nanoparticles. There are several drug-loaded liposomal formulations approved for clinical use that help mitigate harmful effects of life-threatening diseases. Developments in the field of liposomal formulations and drug delivery have made it possible for clinicians and researchers to find therapeutic solutions for complicated medical conditions. A key aspect in the development of drug-loaded liposomes is a careful review of optimization techniques to improve the overall formulation stability and efficacy. Optimization studies help in improving/modulating the various properties of drug-loaded liposomes and are vital for the development of this class of delivery systems. A comprehensive overview of the various process variables and factors involved in the optimization of drug-loaded liposomes is presented in this review. The influence of different independent variables on drug release and loading properties with the application of a statistical experimental design is also explained in this article.

Periodically, liposomes have shown tremendous potential as drug carriers as they are multifunctional nanoparticles with a unique ability to deliver drugs and other therapeutic moieties to target sites in the body. The use of statistical experimental designs and optimization models to develop drug-loaded liposomes is considered the most effective step in formulation development. A careful consideration of various factors and variables in optimizing liposome formulations has been specifically described in this review article. Thorough understanding of different factors that affect drug loading and release in liposomes provides deeper insights in achieving a stable, efficacious drug formulation. There are several new aspects and concepts which need to be explored as part of formulation development and optimization of drug-loaded liposomes and this article hopes to shed light on some important aspects in this scientific journey.

Myocardial ischemia-reperfusion injury released cellular fibronectin containing domain A (CFN-EDA): A destructive positive loop amplifying arterial thrombosis formation and exacerbating myocardial reperfusion injury.

Previous research has identified intravascular platelet thrombi in regions affected by myocardial ischemia-reperfusion (MI/R) injury and neighbouring areas. However, the occurrence of arterial thrombosis in the context of MI/R injury remains unexplored. This study utilizes intravital microscopy to investigate carotid artery thrombosis during MI/R injury in rats, establishing a connection with the presence of prothrombotic cellular fibronectin containing extra domain A (CFN-EDA) protein. Additionally, the study examines samples from patients with coronary artery disease (CAD) both before and after coronary artery bypass grafting (CABG). Levels of CFN-EDA significantly increase following MI with further elevation observed following reperfusion of the ischemic myocardium. Thrombotic events, such as thrombus formation and growth, show a significant increase, while the time to complete cessation of blood flow in the carotid artery significantly decreases following MI/R injury induced by ferric chloride. The acute infusion of purified CFN-EDA protein accelerates in-vivo thrombotic events in healthy rats and significantly enhances in-vitro adenosine diphosphate and collagen-induced platelet aggregation. Treatment with anti-CFN-EDA antibodies protected the rat against MI/R injury and significantly improved cardiac function as evidenced by increased end-systolic pressure-volume relationship slope and preload recruitable stroke work compared to control. Similarly, in a human study, plasma CFN-EDA levels were notably elevated in CAD patients undergoing CABG. Post-surgery, these levels continued to rise over time, alongside cardiac injury biomarkers such as cardiac troponin and B-type natriuretic peptide. The study highlights that increased CFN-EDA due to CAD or MI initiates a destructive positive feedback loop by amplifying arterial thrombus formation, potentially exacerbating MI/R injury.

Bilateral Renal Cell Carcinoma in the Horseshoe Kidney With Metastasis in Gallbladder, Pancreas and Duodenum: A Report of a Rare Case and Literature Review.

Horseshoe kidney is the most common renal fusion anomaly and is associated with various complications, ranging from infections to neoplasms. While renal cell carcinoma (RCC) is the most frequent renal neoplasm in adults, its occurrence in a horseshoe kidney is rare, and bilateral involvement is rarer. Furthermore, RCC metastasizing to organs is known and rare sites of metastasis are also documented. The report presents a unique case of bilateral RCC in a horseshoe kidney with synchronous metastasis to the gallbladder, pancreas, and duodenum. This presentation, involving metastasis to these specific organs, is exceedingly uncommon, making it a rarest of rare possibilities. The current case report underscores the importance of vigilant monitoring and comprehensive evaluation in patients with horseshoe kidneys, as they may be predisposed to unusual complications like RCC and rare site metastasis.

Does high dose statin pretreatment affect global strains in patients undergoing valve replacement.

Purpose: To study the effect of rosuvastatin 40 mg (initiated 7 days prior to surgery) in patients undergoing valve replacement (VR) for rheumatic mitral valve disease on left ventricular (LV) strain and biomarker release kinetics. Methods: In this randomized study, cardiac biomarkers viz. troponin I (TnI), Creatine kinase MB (CK-MB), N-terminal pro B-type natriuretic peptide (NTPBNP) were measured before surgery; and 8, 24 and 48 h postoperatively. Global LV (circumferential, global circumferential strain (GCS); longitudinal, GLS; radial, global radial strain (GRS)) strains were measured preoperatively; and 48 h and 30 days postoperatively. Results: Following VR, Global Longitudinal Strain (GLS), Global Circumferential Strain (GCS) and Global Radial Strain (GRS) declined at 48 h in both statin loaded (SL) and non loaded (NL) groups. The %decline in strain was significantly lower in SL group (% change in GLS 35.8% vs 38.8%, GCS 34% vs 44.1%, GRS 45.7% vs 52.6%; p < 0.001).All strain values improved at 30 days with higher improvement in SL group (GLS -15.92 ± 2.00% vs -12.6 ± 1.66%, GCS -15.12 ± 2.93% vs -13.04 ± 2.44%; GRS 22.12 ± 6.85% vs 19.32 ± 6.48%). While TnI, CKMB, NTPBNP increased following surgery, values at 8, 24 and 48 h were lower in the SL vs. NL group. Mean change (baseline to peak biomarker value) was also significantly lower in SL group.The SL group had shorter hospital and Intensive Care Unit (ICU) stay. On Receiver Operating Characteristic Curve (ROC) analysis, baseline GCS ≤ 14% best predicted postoperative 30 day Left Ventricular Ejection Fraction (LVEF) ≤ 50%. Conclusion: Pre-operative high dose rosuvastatin was "cardioprotective" with favorable effect on LV global strain and release kinetics of biomarkers. These cut-offs (described for the first time for rheumatic VR) can be used as prognostic predictors.

The lytic skeletal lesions: A rare presentation of carcinoma prostate on 18F-fluorodeoxyglucose positron emission tomography/computed tomography.

ABSTRACT: We describe the 18F-fluorodeoxyglucose positron emission tomography/contrast enhanced computed tomography (FDG PET/CECT) images of a 63-year-old male who complained of back pain and was suspected of multiple myeloma based on magnetic resonance imaging. PET/CECT suggested the FDG avid lesion involving prostate, accompanied by multiple lytic skeletal lesions with no evidence to suggest other possible primary site. A bone marrow biopsy suggested a metastatic adenocarcinoma of primary prostatic origin. Post anti-androgen therapy follow-up FDG PET/CT revealed reductions in the metabolic activities and soft tissue components of most of the metastatic skeletal lesions. These images highlight the possible indication of FDG PET/CT in evaluation of prostatic malignancy in era of 68Ga-PSMA.