Allama Iqbal Medical College

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), represents a significant challenge to global health. The management of the disease requires an extended course of antibiotic therapy, spanning a duration of 6 to 9 months. The complexity and duration of these regimens frequently lead to significant adverse effects, gastrointestinal issues, and the development of drug resistance. To address these challenges, the nanoparticulate based inhalable drug delivery system was designed as such by synthesising mannosylated chitosan decorated PLGA nanoparticles loaded with isoniazid (MC-PLGA-INH-PNPs) for targeted pulmonary delivery. Hence, nanoparticle based drug delivery system offers the potential to target and deliver the loaded drug directly into the M.tb infected cells. The prepared and optimised nano-formulation had a particle size of 154.9 ± 21 nm, zeta potential -23.2 ± 0.52 mV and entrapment efficiency of 79.8% ± 0.45. Additionally, the MC-PLGA-INH-PNPs exhibited a sustained drug release profile at physiological pH 7.4 for a period of 24 hr. An in vivo study of the MC-PLGA-INH-PNPs was performed on a mouse model utilising lipopolysaccharide as an inducer. The data obtained from the in vivo studies showed substantial improvements in lung tissues architecture and reduced inflammation. The group of animals treated with the MC-PLGA-INH-PNPs showed significant improvement in restoration of the disease when compared to pure drug treated group. These findings further indicate that these inhalable MC-PLGA-INH-PNPs hold a promising strategy for the treatment of tuberculosis and considerably improves pulmonary drug delivery to the target site. However, detailed investigations and testing of this nano-formulation on other relevant animal models will be essential to successfully translate this concept from laboratory to clinical practice.

Anthracyclines (ANT) are widely used in chemotherapy, but their dose-dependent Cardiotoxicity limits long-term use. Carvedilol, a non-selective beta-blocker, has shown potential as a Cardioprotective agent for patients receiving ANT, though its overall effectiveness remains unclear. This systematic review and meta-analysis aimed to assess the impact of carvedilol on cardiac function and survival in patients with anthracycline-induced Cardiotoxicity.

We performed a comprehensive search of major electronic databases through March 2025 for studies comparing carvedilol with placebo or no treatment in human subjects with ANT-Induced Cardiotoxicity. Primary outcomes included left ventricular ejection fraction (LVEF), left ventricular systolic dysfunction (LVSD), left ventricular systolic and diastolic diameters (LVsD, LVdD), and mortality. Secondary outcomes included echocardiographic and Doppler parameters. Random-effects models were used to calculate standard mean differences (SMDs) and risk ratios (RR) using RevMan 5.4.

A total of fourteen studies were included, thirteen in the meta-analysis and one in the systematic review only, comprising 1,245 participants (carvedilol: 679; control: 566). Carvedilol significantly preserved LVEF (SMD: 0.33, 95% CI: 0.09, 0.58) and reduced the risk of LVSD (RR: 0.26, 95% CI: 0.11, 0.62). It also decreased systolic (SMD: -0.39, 95% CI: -0.53, -0.26) as well as diastolic ventricular diameter (SMD: -0.19, 95% CI: -0.38, -0.00). However, no significant difference in short-term mortality was observed.

Carvedilol appears to protect cardiac function in patients undergoing ANT therapy, though it does not significantly impact mortality. Further research is needed to determine optimal dosing, timing, and long-term survival benefits.