Investigation of the Mesencephalic Astrocyte Derived Neurotrophic Factor-Endoplasmic Reticulum Stress Pathway in Mood Disorders.

Background: Bipolar disorder (BD) has been associated with impaired cellular resilience. Recent studies have shown abnormalities in the unfolded protein response (UPR) in BD. The UPR is the cellular response to endoplasmic reticulum (ER) stress.

Nose-to-brain delivery of lithium via a sprayable in situ-forming hydrogel composed of chelating starch nanoparticles.

While bipolar disorder patients can benefit from lithium therapy, high levels of lithium in the serum can induce undesirable systemic side effects. Intranasal (IN) lithium delivery offers a potential solution to this challenge given its potential to facilitate improved lithium transport to brain when delivered to the olfactory mucosa. Herein, a sprayable, in situ forming nanoparticle network hydrogel (NNH) based on Schiff base interactions between chelator-functionalized oxidized starch nanoparticles (SNPs) and carboxymethyl chitosan (CMCh) is reported that can be deployed within the nasal cavity to release ultra-small penetrative SNPs over time.

Tuning mucoadhesion and mucopenetration in self-assembled poly(lactic acid)-block-poly(oligoethylene glycol methacrylate) block copolymer nanoparticles by controlling side-chain lengths.

The capacity to tune the degree of mucoadhesion and mucopenetration of nanoparticles is essential to improving drug bioavailability, transport, and efficacy at mucosal interfaces. Herein, self-assembled nanoparticles (NPs) fabricated from amphiphilic block copolymers of poly(lactic acid) (PLA) and poly(oligo(ethylene glycol) methacrylate) (POEGMA) with various side chain lengths (PLA-POEGMA) are reported to facilitate tunable mucosal interactions. PLA-POEGMA nanoparticles with long PEG side chain lengths ( = 20, or 40) demonstrated mucoadhesive properties based on rheological synergism, calorimetric tracking of mucin-nanoparticle interactions, and the formation of larger NP-mucin hybrid structures; in contrast, NPs fabricated from block copolymers with shorter PEG side chains ( = 2/8-9 or = 8,9) showed poor mucoadhesion but penetrated through the mucin layer with significantly higher permeation rates (>80%).

Electrospun "Hard-Soft" Interpenetrating Nanofibrous Tissue Scaffolds Facilitating Enhanced Mechanical Strength and Cell Proliferation.

"Soft" hydrogel-based macroporous scaffolds have been widely used in tissue engineering and drug delivery applications due to their hydrated interfaces and macroporous structures, but have drawbacks related to their weak mechanics and often weak adhesion to cells. In contrast, "hard" poly(caprolactone) (PCL) electrospun fibrous networks have desirable mechanical strength and ductility but offer minimal interfacial hydration and thus limited capacity for cell proliferation. Herein, we demonstrate the fabrication of interpenetrating nanofibrous networks based on coelectrospun PCL and poly(oligoethylene glycol methacrylate) (POEGMA) nanofibers that exhibit the mechanical benefits of PCL but the interfacial hydration benefits of hydrogels.

Corked Microcapsules Enabling Controlled Ultrasound-Mediated Protein Delivery.

While ultrasound represents a facile, portable, and noninvasive trigger for drug delivery vehicles, most reported ultrasound-triggered drug delivery vehicles predominately present "burst" release profiles that are hard to control after the initial activation stimulus. Herein, we report a submerged electrospraying technique to fabricate protein-loaded microcapsules in which silica "corks" are embedded within the microcapsule shell. Upon the application of an ultrasound trigger, the corks can be perturbed within the shell, allowing for the release of the protein payload through a phantom tissue mimic to a degree proportional to the number/time of pulses applied.