Glucan Particle Encapsulated Rifampicin for Targeted Delivery to Macrophages

Abstract

Glucan particles (GPs) are 2-4 m spherical, hollow, porous shells extracted from Baker's yeast, Saccharomyces cerevisae. The surface of the GPs is composed primarily of 1,3--glucan and the particles are efficiently phagocytosed via receptor-mediated cell uptake by macrophages, phagocytic cells expressing glucan receptors. The hollow cavity of the GPs allows for efficient absorption and encapsulation of payload molecules. Rifampicin (Rif), a drug used in tuberculosis treatment, was encapsulated by precipitation in GPs and trapped using a calcium alginate or chitosan hydrogel to seal the pores of GPs and slow Rif release. Unplugged GP formulations immediately released Rif following particle resuspension in aqueous buffer. Alginate and chitosan sealing of GPs loaded with Rif was able to extend drug release for 24-72 h. GP-Rif formulations containing 10% w/w Rif/GP plugged with a calcium alginate hydrogel were effective at reducing colony forming units of M. tuberculosis strain mc 2 6020 in infected bone marrow macrophages ~80-90% at 24 and 72 hours. The amount of Rif delivered in the GP formulations was below the free Rif minimal inhibitory concentration demonstrating that GP targeted Rif delivery to macrophages enhances Rif antimicrobial effects. OPEN ACCESSPolymers 2010, 2 682

Controlled-release approaches towards the chemotherapy of tuberculosis

“…These particles are easily phagocytized via receptor-mediated cell uptake by macrophages, wherein phagocytic cells communicate with glucan receptors. 44 The use of GPs for delivery of macromolecules, such as DNA, siRNA, and proteins, has been successfully established both in vitro and in vivo. 45,46 Soto et al have successfully encapsulated the TB antibiotic rifampin in glucan particles by making use of an alginate or chitosan hydrogel to close the GP pores and prolong the drug release.…”

“…45,46 Soto et al have successfully encapsulated the TB antibiotic rifampin in glucan particles by making use of an alginate or chitosan hydrogel to close the GP pores and prolong the drug release. 44 The void holes of the GPs permit the efficient absorption and encapsulation of drugs. They have reported the sustained release for periods of 24-72 hours in vitro and have found that the formulation diminishes the intracellular TB count in infected bone marrow-derived macrophages.…”

“…The amount of rifampin released in the GP formulations was below the free rifampin minimal inhibitory concentration, demonstrating that GP-targeted rifampin delivery to macrophages improves rifampin's therapeutic effects. 44 Figure 5 shows microscopic images of empty GPs and GP-rifampin samples.…”

“…67 Worldwide, osteoarticular tuberculosis accounts for approximately 10%-11% of extrapulmonary TB cases; that is, about 19-38 million cases annually. [44][45][46][47][48] According to WHO, spinal tuberculosis is a cruel form of extrapulmonary tuberculosis and is allocated to category I. According to WHO standards, all cases of spine TB should be treated for at least 6 months.…”

“…69,70 Due to advancements in fixation equipment and technology, surgery on the bone disease foci is recommended. 44 However, a course of multiple drugs is still regrettably obligatory in addition to surgery. The contemporary course of therapy for curing osteoarticular tuberculosis was a 7-28-day preoperative and a postoperative 6-9 month course of multiple anti-TB medicines to strengthen the therapeutic results.…”