Biodegradable containers composed of anionic liposomes and cationic polypeptide vesicles

An electrostatic complexation of liposomes, composed of anionic palmitoyloleoyl phosphatidylserine (POPS ) and zwitterionic dioleoylphophatidylcholine (DOPC), with bilayer vesicles composed of cationic poly(l-lysine)-b-poly(l-leucine) block copolypeptides has been investigated. The complexation was characterized by several physicochemical methods with the following main conclusions: (a) all added liposomes are totally adsorbed on the polypeptide vesicles up to a certain saturation concentration. (b) The calculated number of liposomes per a single polypeptide vesicle is about 60. (c) The liposomes remain intact (i.e., do not leak) after being complexed with the vesicles. (d) Complexes are stable in physiological ionic strength solution with [NaCl] = 0.15 M. (e) The vesicles are effectively digested by proteolytic enzyme trypsin even when covered by liposomes. These findings as well as the high potential for loading of anionic liposomes and cationic vesicles with biologically active compounds make these multi-liposomal complexes promising in the drug delivery field. 1

Radio Frequency-Activated Nanoliposomes for Controlled Combination Drug Delivery

This work was conducted in order to design, characterize, and evaluate stable liposomes containing the hydrophobic drug raloxifene HCl (RAL) and hydrophilic doxycycline HCl (DOX), two potentially synergistic agents for treating osteoporosis and other bone lesions, in conjunction with a radio frequency-induced, hydrophobic magnetic nanoparticle-dependent triggering mechanism for drug release. Both drugs were successfully incorporated into liposomes by lipid film hydration, although combination drug loading compromised liposome stability. Liposome stability was improved by reducing the drug load and by including Pluronics® (PL) in the formulations. DOX did not appear to interact with the phospholipid membranes comprising the liposomes, and its release was maximized in the presence of radio frequency (RF) heating. In contrast, differential scanning calorimetry (DSC) and phosphorus-31 nuclear magnetic resonance ((31)P-NMR) analysis revealed that RAL developed strong interactions with the phospholipid membranes, most notably with lipid phosphate head groups, resulting in significant changes in membrane thermodynamics. Likewise, RAL release from liposomes was minimal, even in the presence of RF heating. These studies may offer useful insights into the design and optimization of multidrug containing liposomes. The effects of RAL on liposome characteristics and drug release performance underscore the importance of appropriate physical-chemical analysis in order to identify and characterize drug-lipid interactions that may profoundly affect liposome properties and performance early in the formulation development process

Self-assembly of nanoparticles into biomimetic capsid-like nanoshells

Nanoscale compartments are one of the foundational elements of living systems. Capsids, carboxysomes, exosomes, vacuoles and other nanoshells easily self-assemble from biomolecules such as lipids or proteins, but not from inorganic nanomaterials because of difficulties with the replication of spherical tiling. Here we show that stabilizer-free polydispersed inorganic nanoparticles (NPs) can spontaneously organize into porous nanoshells. The association of water-soluble CdS NPs into self-limited spherical capsules is the result of scale-modified electrostatic, dispersion and other colloidal forces. They cannot be accurately described by the Derjaguin–Landau–Vervey–Overbeek theory, whereas molecular-dynamics simulations with combined atomistic and coarse-grained description of NPs reveal the emergence of nanoshells and some of their stabilization mechanisms. Morphology of the simulated assemblies formed under different conditions matched nearly perfectly the transmission electron microscopy tomography data. This study bridges the gap between biological and inorganic self-assembling nanosystems and conceptualizes a new pathway to spontaneous compartmentalization for a wide range of inorganic NPs including those existing on prebiotic Earth