Abstract
The propensity of monocytes to migrate into sites of mycobacterium tuberculosis (TB) infection and then become infected themselves makes them potential targets for delivery of drugs intracellularly to the tubercle bacilli reservoir. Conventional TB drugs are less effective because of poor intracellular delivery to this bacterial sanctuary. This study highlights the potential of using semicrystalline delta inulin particles that are readily internalised by monocytes for a monocyte-based drug delivery system. Pyrazinoic acid was successfully attached covalently to the delta inulin particles via a labile linker. The formation of new conjugate and amide bond was confirmed using zeta potential, Proton Nuclear Magnetic Resonance (1HNMR) and Fourier transform infrared spectroscopy (FTIR). Scanning electron microscopy (SEM) confirmed that no significant change in size after conjugation which is an important parameter for monocyte targeting. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) were used to establish the change in thermal properties. The analysis of in-vitro release demonstrated pH-triggered drug cleavage off the delta inulin particles that followed a first-order kinetic process. The efficient targeting ability of the conjugate for RAW 264.7 monocytic cells was supported by cellular uptake studies. Overall, our finding confirmed that semicrystalline delta inulin particles (MPI) can be modified covalently with drugs and such conjugates allow intracellular drug delivery and uptake into monocytes, making this system potentially useful for the treatment of TB.
Highlights
Mycobacterium tuberculosis (Mtb) remains a deadly and contagious human pathogen responsible for tuberculosis which is the leading cause of death from infectious diseases surpassing human immunodeficiency virus infection (HIV) and acquired immune deficiency syndrome (AIDS) according to reports from the Global Tuberculosis Report 2017 [1]
Despite the progress achieved in global TB control, eradication and treatment has been significantly jeopardized by the HIV epidemic [3,4,5] and the emergence of multidrug-resistant TB (MDR) and extensively drug-resistant TB (XDR TB) [6,7]
Artificial Lysosomal Fluid (ALF) and Simulated Body Fluid (SBF) were prepared as reported in the literature [40]. 30 mg MPIEDPCA particles which are equivalent to 3 mL was centrifuged and the supernatant was discarded
Summary
Mycobacterium tuberculosis (Mtb) remains a deadly and contagious human pathogen responsible for tuberculosis which is the leading cause of death from infectious diseases surpassing human immunodeficiency virus infection (HIV) and acquired immune deficiency syndrome (AIDS) according to reports from the Global Tuberculosis Report 2017 [1]. The recruitment of monocytes is crucial for host defences against invading pathogens, but they contribute to the pathogenesis of inflammatory diseases [17] This recruitment, migration, ability to penetrate sites of inflammation, tumours and cross biological barriers, reaching deep hypoxic areas [19,20]; this makes them an important target that can be utilised to deliver drug cargos in the treatment of conditions such as tuberculosis [21,22], HIV [23,24], cancer [25,26], and inflammatory diseases [27].
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