Special Issue "Application Progress of Liposomes in Drug Development".

The second edition of the Special Issue entitled the "Application Progress of Liposomes in Drug Development" featured contributions predominantly focused on leveraging liposomes as enhancers and carriers in drug delivery in the context of cancer treatment, although this was not the initial intent of this Special Issue [...].

Liposomes: The Brave Old World.

Liposomes have been known of for about 60 years, since they were discovered by A [...].

Elastic and Ultradeformable Liposomes for Transdermal Delivery of Active Pharmaceutical Ingredients (APIs).

Administration of active pharmaceutical ingredients (APIs) through the skin, by means of topical drug delivery systems, is an advanced therapeutic approach. As the skin is the largest organ of the human body, primarily acting as a natural protective barrier against permeation of xenobiotics, specific strategies to overcome this barrier are needed. Liposomes are nanometric-sized delivery systems composed of phospholipids, which are key components of cell membranes, making liposomes well tolerated and devoid of toxicity. As their lipid compositions are similar to those of the skin, liposomes are used as topical, dermal, and transdermal delivery systems. However, permeation of the first generation of liposomes through the skin posed some limitations; thus, a second generation of liposomes has emerged, overcoming permeability problems. Various mechanisms of permeation/penetration of elastic/ultra-deformable liposomes into the skin have been proposed; however, debate continues on their extent/mechanisms of permeation/penetration. In vivo bioavailability of an API administered in the form of ultra-deformable liposomes is similar to the bioavailability achieved when the same API is administered in the form of a solution by subcutaneous or epi-cutaneous injection, which demonstrates their applicability in transdermal drug delivery.

Amyloid-ß effects on synapses and memory require AMPA receptor subunit GluA3.

Amyloid-ß (Aß) is a prime suspect for causing cognitive deficits during the early phases of Alzheimer's disease (AD). Experiments in AD mouse models have shown that soluble oligomeric clusters of Aß degrade synapses and impair memory formation. We show that all Aß-driven effects measured in these mice depend on AMPA receptor (AMPAR) subunit GluA3. Hippocampal neurons that lack GluA3 were resistant against Aß-mediated synaptic depression and spine loss. In addition, Aß oligomers blocked long-term synaptic potentiation only in neurons that expressed GluA3. Furthermore, although Aß-overproducing mice showed significant memory impairment, memories in GluA3-deficient congenics remained unaffected. These experiments indicate that the presence of GluA3-containing AMPARs is critical for Aß-mediated synaptic and cognitive deficits.

Motor Learning Requires Purkinje Cell Synaptic Potentiation through Activation of AMPA-Receptor Subunit GluA3.

Accumulating evidence indicates that cerebellar long-term potentiation (LTP) is necessary for procedural learning. However, little is known about its underlying molecular mechanisms. Whereas AMPA receptor (AMPAR) subunit rules for synaptic plasticity have been extensively studied in relation to declarative learning, it is unclear whether these rules apply to cerebellum-dependent motor learning. Here we show that LTP at the parallel-fiber-to-Purkinje-cell synapse and adaptation of the vestibulo-ocular reflex depend not on GluA1- but on GluA3-containing AMPARs. In contrast to the classic form of LTP implicated in declarative memory formation, this form of LTP does not require GluA1-AMPAR trafficking but rather requires changes in open-channel probability of GluA3-AMPARs mediated by cAMP signaling and activation of the protein directly activated by cAMP (Epac). We conclude that vestibulo-cerebellar motor learning is the first form of memory acquisition shown to depend on GluA3-dependent synaptic potentiation by increasing single-channel conductance.

Nanocarrier possibilities for functional targeting of bioactive peptides and proteins: state-of-the-art.

This review attempts to provide an updated compilation of studies reported in the literature pertaining to production of nanocarriers encasing peptides and/or proteins, in a way that helps the reader direct a bibliographic search and develop an integrated perspective of the subject. Highlights are given to bioactive proteins and peptides, with a special focus on those from dairy sources (including physicochemical characteristics and properties, and biopharmaceutical application possibilities of e.g. lactoferrin and glycomacropeptide), as well as to nanocarrier functional targeting. Features associated with micro- and (multiple) nanoemulsions, micellar systems, liposomes and solid lipid nanoparticles, together with biopharmaceutical considerations, are presented in the text in a systematic fashion.