Tuberculosis (TB) is among the greatest public health and safety concerns in the 21st century Mycobacterium tuberculosis, which causes TB, infects alveolar macrophages and uses these cells as one of its primary sites of replication. The current TB treatment regimen, which consists of chemotherapy involving a combination of 3-4 antimicrobials for a duration of 6-12 months, is marked with significant side effects, toxicity, and poor compliance. Targeted drug delivery offers a strategy that can overcome many of the problems of current TB treatment by specifically targeting infected macrophages. Recent advances in nanotechnology and material science have opened an avenue to explore drug carriers that actively and passively target macrophages. This approach can increase the drug penetration into macrophages by using ligands on the nanocarrier that interact with specific receptors for macrophages. This review encompasses the recent development of drug carriers specifically targeting macrophages actively and passively. Future directions and challenges associated with development of effective TB treatment are also discussed.

Pseudomonas aeruginosa is the leading nosocomial and community-acquired pathogen causing a plethora of acute and chronic infections. The Centers for Disease Control and Prevention has designated multidrug-resistant isolates of P. aeruginosa as a serious threat. A novel delivery vehicle capable of specifically targeting  P. aeruginosa, and encapsulating antimicrobials, may address the challenges associated with these infections. We have developed hetero-multivalent targeted liposomes functionalized with host cell glycans to increase the delivery of antibiotics to the site of infection. Previously, we have demonstrated that compared with monovalent liposomes, these hetero-multivalent liposomes bind with higher affinity to P. aeruginosa. Here, compared with nontargeted liposomes, we have shown that greater numbers of targeted liposomes are found in the circulation, as well as at the site of P. aeruginosa (PAO1) infection in the thighs of CD-1 mice. No significant difference was found in the uptake of targeted, nontargeted, and PEGylated liposomes by J774.A1 macrophages. Ciprofloxacin-loaded liposomes were formulated and characterized for size, encapsulation, loading, and drug release. In vitro antimicrobial efficacy was assessed using CLSI broth microdilution assays and time-kill kinetics. Lastly, PAO1-inoculated mice treated with ciprofloxacin-loaded, hetero-multivalent targeted liposomes survived longer than mice treated with ciprofloxacin-loaded, monovalent targeted, or nontargeted liposomes and free ciprofloxacin. Thus, liposomes functionalized with host cell glycans target P. aeruginosa resulting in increased retention of the liposomes in the circulation, accumulation at the site of infection, and increased survival time in a mouse surgical site infection model. Consequently, this formulation strategy may improve outcomes in patients infected with P. aeruginosa.

Conventional solution-phase method currently employed for the production of Antibody-drug Conjugates (ADC) has certain drawbacks, which makes production inefficient and cost extensive process. In this study, we developed a rigorous cost model for an intensified solid-phase production method utilizing a packed bed resin column to carry out all the steps involved in the production of ADC, at an industrial scale. The aim of this study was to find a suitable operating region (column length and feed velocity) to minimize the cost of ADC production. Simulation results showed that productivity was maximum when the process was operated at a linear velocity ranging between 120-140 cm/hr and unit cost of ADC production was minimum when column length was 60 cm and operated at 100 cm/hr. We found that production cost is highly dependent on monoclonal antibody (mAb) cost, followed by cytotoxic drug as being the second-highest contributor to the overall production cost.

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