Soft Interaction in Liposome Nanocarriers for Therapeutic Drug Delivery

Abstract

The development of smart nanocarriers for the delivery of therapeutic drugs has experienced considerable expansion in recent decades, with the development of new medicines devoted to cancer treatment. In this respect a wide range of strategies can be developed by employing liposome nanocarriers with desired physico-chemical properties that, by exploiting a combination of a number of suitable soft interactions, can facilitate the transit through the biological barriers from the point of administration up to the site of drug action. As a result, the materials engineer has generated through the bottom up approach a variety of supramolecular nanocarriers for the encapsulation and controlled delivery of therapeutics which have revealed beneficial developments for stabilizing drug compounds, overcoming impediments to cellular and tissue uptake, and improving biodistribution of therapeutic compounds to target sites. Herein we present recent advances in liposome drug delivery by analyzing the main structural features of liposome nanocarriers which strongly influence their interaction in solution. More specifically, we will focus on the analysis of the relevant soft interactions involved in drug delivery processes which are responsible of main behaviour of soft nanocarriers in complex physiological fluids. Investigation of the interaction between liposomes at the molecular level can be considered an important platform for the modeling of the molecular recognition processes occurring between cells. Some relevant strategies to overcome the biological barriers during the drug delivery of the nanocarriers are presented which outline the main structure-properties relationships as well as their advantages (and drawbacks) in therapeutic and biomedical applications.

Keywords: drug delivery; liposomes; nanotechnology; phospholipids vesicles systems.

Figure 1

Relevant shape factor influencing nanocarrier morphology. Aggregate structures of amphilphilic molecules can be predicted from the critical packing parameter Cpp.

Figure 2

Schematic representation of the charge distribution around the charged surface of a liposome. The electrical double layer (EDL) is composed of a layer of ions strongly bound to the charged surface (Stern layer) and an adjacent region of loosely associated mobile ions (diffuse layer).

Figure 3

Models for the heterotopic aggregates formed by the self-assembly of anionic porphyrins (HTTPS) entangled in cationic amphiphilic modified cyclodextrins (SC6CDNH2) (A), at a different porphyrins/cyclodextrins (TPPS/SC6CDNH2) ratio. Reduction of the relative amount of modified cyclodextrin causes an increase in aggregate dimension as evidenced at the different ratio [TPPS/SC6CDNH2] = 1:50 (B), 1:2 (C), and 1:1 (D) [58].

Figure 4

Schematic representation of the PEGylated phospholipid (DSPE-PEG2000) 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000] ammonium salt (A). View of sterically stabilised lipid bilayers (B). PEG, polyethylene glycol.

Figure 5

Sketch of the Derjaguin–Landau–Verwey–Overbeek (DLVO)-type interaction energy as a function of particle separation. The net energy is given by the sum of the double layer repulsion V_R represented by a Yukawa type potential (electrostatic repulsion screened by ionic species in solution) and the Van der Waals attractive forces potential V_A.

Figure 6

Hydrogen bond mechanism (solvation-desolvation) involved before (A) and after (B) the formation and structural organization of a ligand-protein complex.

Figure 7

Schematic representation of the interaction of biotin with the tetrameric protein streptavidin.

Figure 8

Representation of the aggregation of biotinylated liposomes induced by the tetrameric streptavidin protein.

Figure 9

Schematic representation of the deoxyribonucleic acids (DNA)-induced vesicle fusion process [90].

Figure 10

Chemical structures of drug molecules employed in liposomal formulations for clinical trials in the treatment of different typology of cancer.

Figure 11

Schematic representation of the different types of liposomal drug delivery systems: Charge and polymer stabilized (A), targeted (B), and theranostic (C) liposomes.