[A new therapy concept for the treatment of dry eye--the usefulness of phospholipid liposomes]. / Ein neues Therapiekonzept zur Behandlung des Trockenen Auges--die Verwendung von Phospholipid-Liposomen.

BACKGROUND: Most of the eye drops currently used replace only the aqueous phase of the tear film. But, due to the fact that, with approximately 80 % of the patients with a dry eye, a disturbance of the lipid phase is present, an approach for new treatment methods needed to be found. We examined a new therapy concept with an eye spray containing liposomes for the therapy of the "dry eye" in a long-term study. GOAL: An examination of the effectiveness of a liposome eye spray (TEARS AGAIN, Optima Pharmaceutical GmbH, Germany) in patients with "dry eye" compared with a spray containing a balanced salt solution was carried out. METHODS: Between August 2003 and May 2004 a double-blind study with 382 patients was accomplished. The treatment group (V; n = 191) was compared with the control group (K; n = 191) for a period of 6 months regarding the following examination criteria: eyelid edge parallel conjunctival folds (LIPCOF), BREAK UP time (BUT), Schirmer I test, best corrected visual acuity, as well as slit lamp findings of the cornea and conjunctiva. Follow-up was after 4 weeks and 6 months. The statistical analysis was performed with the statistical program SPSS v.11.5. RESULTS: The examined parameters such as LIPCOF, BUT and Schirmer were significantly better in the treatment group than in the control group. We found likewise significant improvements of the inflammations of the edge of eyelid with a remarkable decrease of around 89.5 %. Questioning of the patients resulted in, among other things, the belief that the liposome eye spray led altogether to a clear subjective improvement of the symptoms in 72 % of the cases, although an initial burning sensation was mentioned after the application. All patients were of the opinion that application with a spray is more favourably and more pleasant than teardrops. CONCLUSION: The liposome tear substitute shows statistically significant advantages against a balanced salt solution. This new liposome eye spray represents a new, revolutionary and effective procedure in the therapy of the "dry eye". Considering the disturbance of the lipid phase in 80 % of the patients, TEARS AGAIN ought to be a first choice treatment.

Effects of phospholipid vesicles (liposomes) on cAMP levels in the rat cerebral cortex.

We studied the effects of two types of liposomes (cholate-free liposomes and cholate-containing liposomes) on control (in the presence of 3-isobutyl-1 methyl xanthine [IBMX], a phosphodiesterase inhibitor) and stimulated (IBMX plus isoprenaline) cyclic 3',5'-adenosine monophosphate (cAMP) accumulation in slices of rat cerebral cortex. Our purpose was to examine whether or not liposomes with different lipid constituents modify levels of cAMP in vitro. Liposomes at low concentrations had a significant inhibitory effect on cAMP accumulation in brain tissue. This inhibition was concentration-dependent. Cholate-containing liposomes had a greater inhibitory effect at higher concentrations. Liposomes also inhibited cAMP accumulation in a dose-dependent manner when the tissues were preincubated with ouabain, a Na(+)-K(+)-ATPase inhibitor. These results demonstrate that, in rat brain, liposomes alone modified important biochemical responses such as the adenylyl cyclase-cAMP system coupled to beta-adrenoceptors. The significance of these findings for the mechanism of the action of liposomes is discussed.

Interaction of liposomes with human epidermis reconstructed in vitro.

Upon topical application of liposomes of the large unilamellar vesicle type to human epidermis reconstructed in vitro, there is a dose-dependent alteration of the morphology of both the stratum corneum and the living part of the epidermis. In particular, shrunken lipid droplets are found between corneocytes and keratinocytes. Sometimes, corneocytes show inclusions reminiscent of 'cholesterol crystals'. Corneocytes, moreover, show a decreased density. Both corneocytes of the various layers of the stratum corneum and keratinocytes belonging to the uppermost layer of the living epidermis show particularly osmophilic membranes, indicating lipid transfer. Intact liposomes or their remnants can sometimes be seen between corneocytes of the upper strata. The presence of liposomal lipid within the stratum corneum is supported by the presence of gold particles used as a marker. There is, however, no evidence for the uptake of intact liposomes by the living epidermis, or their passage through this compartment of the skin.

Evidence for the phagocytosis of intact oligolamellar liposomes by human keratinocytes in vitro and consecutive intracellular disintegration.

While there is evidence for the use of liposomes as drug carriers upon topical application to the skin, the underlying mechanisms are far from being clear. Therefore human keratinocytes grown in vitro were exposed to large oligolamellar liposomes. After attachment and invagination these particles can be found unchanged within the cytoplasm both inside and outside of lysosomes. If incorporated into lysosomes the structural lipids can be disintegrated and spread within the entire phagolysosome. Gold labeling adds further to the hypothesis of intact uptake of liposomes by the living cells of the human epidermis.