Mitotane liposomes for potential treatment of adrenal cortical carcinoma: ex vivo intestinal permeation and in vivo bioavailability.

The adrenal cortical carcinoma (ACC) treatment, for which mitotane (o,p'-DDD) is the drug of choice, still remains a challenge both because of the well-known solubility problems of the drug, and its serious side effects. Mitotane is currently administered as oral tablets. The loading of mitotane into nanocarriers has been suggested as a way to circumvent the low solubility of the drug and its limited oral bioavailability. In this work, we have developed liposomes containing mitotane to enhance its intestinal absorption and oral bioavailability. Liposomes were produced by spray-drying of a mixture of phospholipids and the developed formulation was optimized by studying the degree of crystallinity, spray-drying conditions, phospholipid/mitotane ratio, and influence of mannitol in the hydrating ethanolic solution. An optimal liposomal formulation was produced with a phospholipid:mitotane combination (3.34:1), exhibiting a mean hydrodynamic diameter around 1 µm and spherical shape. The produced mitotane liposomes were re-suspended by hydrating the spray-dried powders in a stirred tank, and tested their intestinal permeability (ex vivo) and relative bioavailability (in vivo), against a free drug solution (with or without Trigliceril®CM). Our results support the conclusion that the loading of mitotane in liposomes enhanced its intestinal absorption and relative bioavailability.

Elastic liposomes containing benzophenone-3 for sun protection factor enhancement.

This work was focused on the loading of benzophenone-3 in elastic liposomes composed of egg phosphatidylcholine and cholesterol, prepared by the Bangham method. Samples were characterized in terms of particle size, polydispersity index (PI), zeta potential, encapsulation efficiency and in vitro photoprotection properties. The extrusion of liposomes loading benzophenone-3 produced reduced-size (100 nm) elastic liposomes with a PI of 0.2. The active was loaded with a concentration of 20.34% (m/m) revealing changes in the ultraviolet properties after loading. On the basis of these results, it can be anticipated that liposomes are able to improve sun protector factor in vitro compared the free active.

Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes.

BACKGROUND: The greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally. RESULTS: We developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65) or complexed (COMP-hsp65), and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 microg of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-gamma and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 microg). CONCLUSION: Our objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this infectious disease.

Retinyl palmitate flexible polymeric nanocapsules: characterization and permeation studies.

Polymeric nanocapsules with elastic characteristics were prepared by the pre-formed polymer interfacial deposition method. The system consists of an oily core of retinyl palmitate with Span 60 and a polymeric wall of poly(D,L-lactide) (PLA). A narrow size distribution (215 nm, P.D.I. 0.10) was showed by dynamic light scattering (DLS) analyses. Particle deformability was observed by transmission electron microscopy (TEM) images and permeation of the particles through two superposed membranes of smaller pore diameters. Permeation studies were achieved using plastic surgery abdominal human skin by Franz diffusion cell. Retinyl palmitate permeates into deep skin layers. Besides, a PLA fluorescent derivative conjugated with Nile blue dye by an amide covalent bound was additionally obtained. Permeation profile of the nanocapsules with the fluorescent polymer was evaluated by confocal laser scanning microscopy (CLSM). The CLSM showed that nanocapsules were distributed uniformly, suggesting that the permeation mechanism through skin is intercellular. Thus, the use of these nanocapsules may be a feasible strategy to enhance the permeation of actives into the skin when delivery to deep layers is aimed.