Pace University, United States
pp. 101 - 104
Keywords: liposomes, nanogels, supramolecular assembly, lipobeads, drug delivery systems
Both polymeric and liposomal drug delivery systems tend to develop in the direction of increasing complexity, i.e. in accord with our understanding of the complex biological mechanisms prevailing in situ. To this point, one can conclude that the next level of complexity is multifunctional and multicompartmental drug delivery formulations achievable experimentally in laboratory. A logical combination of polymeric and liposomal beaded nanoscopic systems is the arrangements of the lipid bilayer/hydrogel assembly (lipobeads) – the lipid vesicles filled with polymeric networks. The data available in literature showed that drug-loaded lipobeads (i) in addition to all the important benefits of polymeric and liposomal drug carriers, possess mechanical stability and environmental responsiveness in one construct, (ii) exhibit no toxicity on intravenously administered mice, (iii) accumulate both in the area surrounding tumor and within the tumor itself outside the vasculature, and (iv) demonstrate high therapeutic activity at the targeted site. Moreover, the bi-compartmental structure of lipobeads can provide a number of novel and unique options (new schemes of drug release, consecutive multistep triggering, and combined drug delivery systems). However, bringing a new drug through all stages of development (discovery, clinical testing, and regulatory approval) is an expensive and time-consuming process. For example, for liposomal drug delivery systems it took almost 40 years from the concept to the established technology and clinical acceptance. The concept of the lipobeads proposed about 30 years ago is still at the stage of discovery and development. This presentation addresses three main issues, which should be recognized to push the concept of lipobeads to the next level of development (clinical trials): (i) two major methods for lipobeads’ synthesis, (ii) mechanisms of controlled drug release using the lipobeads with an environmentally responsive hydrogel core, (iii) the future of lipobeads in terms of their applications as a recognized combination and multifunctional drug delivery system. On the one hand, the original microscopic (optical, fluorescence, confocal, AFM) data on nano-(< 1 um) and giant (> 1 um) lipobeads demonstrate their technological achievability. On the other hand, the ideas on the conceptually new drug delivery systems, new mechanisms of lipobead internalization into the cell and mechanisms of drug release regulated by specific signaling support the expectations that additional expenses on their production could be reimbursed by the potential advantages of their use.