Getting into the brain: liposome-based strategies for effective drug delivery across the blood-brain barrier.

This review summarizes articles that have been reported in literature on liposome-based strategies for effective drug delivery across the blood-brain barrier. Due to their unique physicochemical characteristics, liposomes have been widely investigated for their application in drug delivery and in vivo bioimaging for the treatment and/or diagnosis of neurological diseases, such as Alzheimer's, Parkinson's, stroke, and glioma. Several strategies have been used to deliver drug and/or imaging agents to the brain. Covalent ligation of such macromolecules as peptides, antibodies, and RNA aptamers is an effective method for receptor-targeting liposomes, which allows their blood-brain barrier penetration and/or the delivery of their therapeutic molecule specifically to the disease site. Additionally, methods have been employed for the development of liposomes that can respond to external stimuli. It can be concluded that the development of liposomes for brain delivery is still in its infancy, although these systems have the potential to revolutionize the ways in which medicine is administered.

Hybrid materials from intermolecular associations between cationic lipid and polymers.

Intermolecular associations between a cationic lipid and two model polymers were evaluated from preparation and characterization of hybrid thin films cast on silicon wafers. The novel materials were prepared by spin-coating of a chloroformic solution of lipid and polymer on silicon wafer. Polymers tested for miscibility with the cationic lipid dioctadecyldimethylammonium bromide (DODAB) were polystyrene (PS) and poly(methyl methacrylate) (PMMA). The films thus obtained were characterized by ellipsometry, wettability, optical and atomic force microscopy, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and activity against Escherichia coli. Whereas intermolecular ion-dipole interactions were available for the PMMA-DODAB interacting pair producing smooth PMMA-DODAB films, the absence of such interactions for PS-DODAB films caused lipid segregation, poor film stability (detachment from the silicon wafer) and large rugosity. In addition, the well-established but still remarkable antimicrobial DODAB properties were transferred to the novel hybrid PMMA/DODAB coating, which is demonstrated to be highly effective against E. coli.

Cationic nanoparticles for delivery of amphotericin B: preparation, characterization and activity in vitro.

BACKGROUND: Particulate systems are well known to be able to deliver drugs with high efficiency and fewer adverse side effects, possibly by endocytosis of the drug carriers. On the other hand, cationic compounds and assemblies exhibit a general antimicrobial action. In this work, cationic nanoparticles built from drug, cationic lipid and polyelectrolytes are shown to be excellent and active carriers of amphotericin B against C. albicans. RESULTS: Assemblies of amphotericin B and cationic lipid at extreme drug to lipid molar ratios were wrapped by polyelectrolytes forming cationic nanoparticles of high colloid stability and fungicidal activity against Candida albicans. Experimental strategy involved dynamic light scattering for particle sizing, zeta-potential analysis, colloid stability, determination of AmB aggregation state by optical spectra and determination of activity against Candida albicans in vitro from cfu countings. CONCLUSION: Novel and effective cationic particles delivered amphotericin B to C. albicans in vitro with optimal efficiency seldom achieved from drug, cationic lipid or cationic polyelectrolyte in separate. The multiple assembly of antibiotic, cationic lipid and cationic polyelctrolyte, consecutively nanostructured in each particle produced a strategical and effective attack against the fungus cells.

Cationic lipids and surfactants as antifungal agents: mode of action.

OBJECTIVES: To determine the mechanism of antimicrobial action for cationic lipid dioctadecyldimethylammonium bromide (DODAB) and hexadecyltrimethylammonium bromide (CTAB) against Candida albicans. METHODS: Determination of DODAB or CTAB adsorption isotherms; cell viability; cell electrophoretic mobility (EM); and leakage of small phosphorylated compounds, proteins or DNA from fungus or haemoglobin from erythrocytes. RESULTS: High affinity isotherms for CTAB and DODAB adsorption onto fungus cells (10(8) cfu/mL) yield limiting adsorption at 7.8 and 3.7 x 10(9) molecules per cell, respectively. Negatively charged C. albicans cells (10(6) cfu/mL) remain viable whereas positively charged ones die. At 0.3 mM CTAB or 0.01 mM DODAB, EM is zero and fungus viability is 50%. Cells start to die at submicellar CTAB concentrations and fungus lysis does not play a significant role in the mechanism of antifungal action. Over 0.1-10 mM CTAB or DODAB, there is no leakage of tested compounds from C. albicans cells despite the low cell viability. In contrast to the fungus, under isotonic conditions, cationic amphiphiles induce haemolysis over a range of low DODAB (>0.01 mM) and CTAB (>0.001 mM) concentrations. CONCLUSIONS: The critical phenomenon determining antifungal effect of cationic surfactants and lipids is not cell lysis but rather the change of cell surface charge from negative to positive.

Assembly of a model hydrophobic drug into cationic bilayer fragments.

Our previous work has shown that dioctadecyldimethylammonium bromide (DODAB) bilayer fragments (BF) presented antimicrobial activity, solubilized fungicides, e.g., amphotericin B and miconazole (MCZ), stabilized hydrophobic drug particles and were effective in vivo. Here, the interaction between MCZ and DODAB BF is evaluated from determination of BF loading capacity and effects of drug-to-lipid molar proportion (MP) on particle size, zeta potential and gel-to-liquid-crystalline phase transition T(m). DODAB BF solubilized MCZ over a range of MP. BF loading capacity was 0.5 mM MCZ at 5 mM DODAB. Above this limit, the drug aggregated in the dispersion. At pH 6.3, BF zeta potentials decreased with MP, suggesting insertion of deprotonated drug into the bilayer. MCZ optical spectra in BF were similar to those in best organic solvent, confirming drug solubilization. At MP 1:10, BF T(m) remained unchanged, suggesting drug capture at BF hydrophobic edges. At MP 1:10, T(m) decreased, showing MCZ insertion into DODAB bilayer. However, drug was expelled from the bilayer core upon lowering temperature. Minimal fungicidal concentrations against C. albicans were synergically reduced by 10 times for drug/BF.