Researchers have designed tiny spheres capable of delivering isoniazid, a drug that fights lung cells infected with tuberculosis1. They constructed the spheres from amino acid, sugar and polysaccharide-derived salt.
The bacterium that causes tuberculosis reaches the lungs through inhalation. In the lungs, macrophages, a type of immune cells, engulf the bacteria. In recent years, the bacterium has grown resistant to a range of drugs. This has led researchers to design drug-delivery vehicles such as poly-l-lysine (PLL). Although PLL is capable of attaching to cell membranes for drug delivery, its high charge density and molecular weight can cause toxic side-effects.
To devise a safer drug-delivery vehicle, the researchers mixed lysine and mannose to generate mannosylated lysine (m-LS). They added sodium alginate (SA), a sodium salt derived from a polysaccharide, to form a white, odourless and fibrous co-polymer, m-LS-co-SA. The researchers produced four batches (MS1, MS2, MS3 and MS4) of microspheres based on m LS-co-SA. They loaded the microspheres with isoniazid and carried out drug-release studies.
Microspheres of MS1 and MS2 provided a high initial release of the isoniazid. During the first 1 hour, MS1 and MS2 provided a cumulative drug release of 67% and 40%, respectively. No drug release was observed from MS1 after 8 hours. Within 15 minutes of administration, strong intracellular fluorescence was observed in the cytosol of alveolar macrophages.
Microsphere formulations can reduce toxic complications arising from fluctuations in the plasma levels of drugs. The microspheres facilitated the prolonged presence of isoniazid into the blood, thus inhibiting the intracellular multiplication of the pathogen and eliminating the microbial load from other infected tissue.
The researchers say that these microspheres, with their respirable size range, can have a wide variety of applications for fighting diseases mediated by macrophages.
The authors of this work are from: Department of Pharmaceutics, Institute of Technology, and Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Uttar Pradesh, India.
