Simultaneous liposomal encapsulation of antibiotics and proteins: Co-loading and characterization of rifampicin and Human Serum Albumin in soy-liposomes

The recurrent development of resistance to antimicrobial agents threatens the ability for successful treatment of infectious diseases. Hydrophobic antibiotics such as rifampicin (Rif) are particularly affected due to poor bioavailability. On the other hand, proteins play important roles in drug delivery and release. Further, the combination of antimicrobials with therapeutic proteins and their encapsulation in liposomes seems a promising approach for improvement of antimicrobial efficacy. This study aimed to encapsulate Rif simultaneously with a large protein, Human Serum Albumin (HSA) in liposomes made from an inexpensive crude soy lecithin (CSL). Dual liposomes (Rif-HSA-lip) were prepared using a reverse phase evaporation method. The effect of lipid composition and HSA concentration on Rif loading was also investigated. Physicochemical properties, stability of Rif-HSA-lip and Rif release profiles were evaluated. A good encapsulation efficiency was observed (59% for Rif), despite the presence of bulky HSA. This paves the way for encapsulation strategies of other "biologics". The in vitro release profile for Rif from the Rif-HSA-lip was improved and the freeze-dried formulation exhibited good shelf stability over liposomes with no HSA. The presence of HSA in the liposomal membrane is encouraging for potential targeted delivery studies. This study represents an illustrative example of co-loading of antibiotics and proteins into liposomes, which could lead to the development of novel therapeutic tools for tackling antimicrobial resistance.