Phase 3 efficacy and safety trial of proposed liraglutide biosimilar for reduction of glycosylated hemoglobin (HbA1c) in patients with Type 2 diabetes mellitus.

Liraglutide is indicated for glycaemic control in adults with Type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise. A proposed biosimilar of liraglutide (Levim Liraglutide) was investigated for efficacy & safety in a phase 3 study against the originator reference liraglutide (Victoza®) manufactured by Novo Nordisk A/S, Denmark. Patients aged 18-65 years of age with glycosylated hemoglobin (HbA1c) between 7 and 10 %, among other criteria, were included in the study. Patients were randomized 1:1 to receive daily doses of either Levim liraglutide or reference liraglutide for 24 weeks. The least square mean (standard error, SE) for the primary efficacy endpoint of reduction in HbA1c% at Week 24 was -1.09 (0.15)% for Levim liraglutide group and -1.04 (0.14)% for reference liraglutide. The upper bound of the confidence interval for treatment difference was less than the non-inferiority margin of 0.4 % at one-sided alpha of 0.025 (P-value = 0.0003). The secondary endpoints for proportion of patients achieving reduction in HbA1c, glycaemic level and weight, changes in cardiovascular parameters and the overall safety profiles of the study drugs were comparable. Levim liraglutide demonstrated non-inferior efficacy and similar safety to reference liraglutide and may be an option in treatment of T2DM (CTRI.nic.in, no. CTRI/2022/02/040261).

Gold nanoparticle based X-ray contrast agent for tumor imaging in mice and dog: a potential nano-platform for computer tomography theranostics.

The goal of our study was to demonstrate the utility of nanocrystalline gold as an X-ray contrast agent for imaging tumor in living subjects. Even though significant progress has been achieved in this area by researchers, clinical translation remains challenging. Here, we investigated biocompatible gum Arabic stabilized gold nanocrystals (GA-AuNPs) as X-ray contrast agent in tumor bearing mice and dog. Single intratumoral injections of GA-AuNP resulted in X-ray contrast change of -26 HU in the tumor region after 1 hour post-injection period. Subsequently, five intratumoral injections were performed in the mice. The change in CT number in tumor region is not progressive; rather it reaches a saturation point after fourth injection. These data suggested that accumulation of GA-AuNP reaches a threshold limit within a short time period (5 h), and is retained in the tumor tissue for the rest of the period of investigation. A pilot study was conducted in a client-owned dog presented with collision tumor of thyroid carcinoma and osteosarcoma. In this study, GA-AuNP was injected intratumorally in dog and a contrast enhancement of 12 deltaHU was observed. The CT images of both mice and dog clearly demonstrated that GA-AuNP was effectively distributed and retained throughout the tumor site. The CT data obtained by the present study would provide the crucial dosimetry information for strategic therapy planning using this construct. Both mice and dog did not show any clinical changes, thereby confirming that GA-AuNP did not induce toxicity and can be explored for future clinical applications.

Laminin receptor specific therapeutic gold nanoparticles (198AuNP-EGCg) show efficacy in treating prostate cancer.

Systemic delivery of therapeutic agents to solid tumors is hindered by vascular and interstitial barriers. We hypothesized that prostate tumor specific epigallocatechin-gallate (EGCg) functionalized radioactive gold nanoparticles, when delivered intratumorally (IT), would circumvent transport barriers, resulting in targeted delivery of therapeutic payloads. The results described herein support our hypothesis. We report the development of inherently therapeutic gold nanoparticles derived from the Au-198 isotope; the range of the (198)Au ß-particle (approximately 11 mm in tissue or approximately 1100 cell diameters) is sufficiently long to provide cross-fire effects of a radiation dose delivered to cells within the prostate gland and short enough to minimize the radiation dose to critical tissues near the periphery of the capsule. The formulation of biocompatible (198)AuNPs utilizes the redox chemistry of prostate tumor specific phytochemical EGCg as it converts gold salt into gold nanoparticles and also selectively binds with excellent affinity to Laminin67R receptors, which are over expressed in prostate tumor cells. Pharmacokinetic studies in PC-3 xenograft SCID mice showed approximately 72% retention of (198)AuNP-EGCg in tumors 24 h after intratumoral administration. Therapeutic studies showed 80% reduction of tumor volumes after 28 d demonstrating significant inhibition of tumor growth compared to controls. This innovative nanotechnological approach serves as a basis for designing biocompatible target specific antineoplastic agents. This novel intratumorally injectable (198)AuNP-EGCg nanotherapeutic agent may provide significant advances in oncology for use as an effective treatment for prostate and other solid tumors.