An eco friendly approach for the development of a dipeptide based anti-TB drug nanocomposites: A greener approach in drug delivery system for pulmonary delivery

Abstract

The conventional anti tubercular (anti-TB) treatment strategies constitute challenges in terms of patient compliance and treatment outcomes. Nano-therapeutics is an emerging field with increasing demand for the therapeutic management of tuberculosis (TB) and the challenges over acquired drug toxicity and poor availability. Nevertheless, studies based on nanopeptide drug carrier for the delivery of anti-TB drugs are scanty. The present work emphasizes on the development of a nanocarrier system through hydrothermal process for encapsulating anti-TB drugs (rifampicin, isoniazid, pyrazinamide, ethambutol) using carnosine dipeptide for the potential therapeutic application. The carnosine-anti-TB drug nanocomposites were synthesized by treating native carnosine and anti-TB drugs at an equal ratio (1:1) incubated at 65°C for 30 min (pH 5.3). The hybrid clusters were freeze dried and used further for characterization (physiochemical, biological, morphology and in silico methods). The structural and functional annotations of carnosine and anti-TB drug nanocomposites were confirmed from its terminal amine absorption stretching’s and its amino group fingerprinting regions. The homogenous nature of carnosine-anti-TB drug complexes in solutions was demonstrated with the particle size (>1 μm), that is suitable for macrophage uptake. SEM analysis demonstrated the interactions and functional group orientation between carnosine and anti-TB drugs during the self-assembly process. The drug release profile indicated that the carnosine-drug conjugation promoted the sustained release compared to free drugs. The quantum mechanical calculations define the structural modelling of drugs with carnosine to obtain a stable energy-minimized conformation. To conclude, the developed carnosine- anti-TB drug nanoclusters with enhanced stability and uniformity in size makes them suitable for macrophage uptake and targeted delivery approaches during TB treatment.