Comparative investigation of sublingual tablets containing oleic acid-conjugated leuprolide nanoparticles and permeation enhancers on disintegration, release rate, permeability and pharmacokinetics in beagle dogs.

To overcome invasive injectables and low oral bioavailability issues of peptide drug, leuprolide (LEU), sublingual tablets was challenged by forming deformable and self-assembled LEU nanoparticles with permeation enhancers (PEs). LEU-oleic acid (OA) nanoparticles (LON) was prepared via self-assembly of LEU-OA conjugates (LOC), whereas deformable LON (d-LON) was prepared by incorporating α-phosphatidylcholine (PC) into LON. Effect of LEU forms (LEU, LOC, LON, and d-LON) and seven GRAS (Generally Recognized As Safe)-listed permeation enhancers (PEs) were screened using a Franz diffusion cell with PermeaPad® membrane.

Albumin Corona Overturns Long-Acting Behaviors of Myristic Acid-Conjugated Quetiapine Nanosuspension.

This work aimed to investigate the interaction of a self-assembled myristic acid-conjugated quetiapine nanosuspension (QMN) with human serum albumin and its overturning effect on QMN's long-acting performance. Albumin corona formation modified the physicochemical properties and pharmacokinetic profile of QMN by overturning its pH-responsiveness and nano-aggregation behavior. The adsorption of albumin on QMN is initially triggered by electrostatic forces and later by hydrophobic-hydrophobic interactions with the conformational change of the albumin structure.

Triple synergistic cancer targeting strategies utilizing redox-sensitive fattigated hyaluronic acid nanoparticles encapsulating doxorubicin.

Antitumor potentials of dietary oleic acid (OA), primarily through enhancing intracellular lipid accumulation in various human cancers are hindered by poor selectivity and tumor targetability. Cancer cells are also challenged by high concentration of glutathione (GSH) and favorable binding affinity of hyaluronic acid (HA) to the CD44 (acidic cell surface adhesion protein) receptor. A novel conjugate (HA-CYS-OA, HOC) was synthesized by linking GSH-sensitive cystamine (CYS) to OA and HA.

Comparative stabilization mechanism of self-assembling fattigated gelatin, micellar polyethylene glycol hexadecyl ether, and electrostatic interactive xanthan gum for aqueous labile decitabine.

Decitabine (DCB) is very unstable in aqueous solutions because of the opening of the N-5 and C-6 aza-ring. The objective of this study was to investigate a stabilization mechanism of aqueous-labile decitabine (DCB) with three different materials by preparing binary spray dried powders (SDs): self-assembling fattigated gelatin-oleic acid conjugate (GOC), micellar polyethylene glycol hexadecyl ether (Brij® 58), nonionic surfactant and electrostatically interactive xanthan gum (XA), an anionic polysaccharide. GOC was synthesized by covalently conjugating oleic acid with gelatin.

Long-term controlled release with reduced initial burst release utilizing calcium ion-triggering nanoaggregates of pasireotide-loaded fattigated albumin nanoparticles.

The aim of this study was to investigate the long-term controlled release of peptide-loaded fattigated albumin nanoparticles via calcium ion-triggering nanoaggregation with minimal initial burst release. Fattigated albumin nanoparticles were prepared via sonication by the self-assembly of human serum albumin (HSA)-oleic acid conjugates (AOC) with three different substitution ratios of oleic acid (OA) to modulate hydrophobicity. Then, pasireotide pamoate (PAS) as a model peptide was encapsulated into the hydrophobic core of HSA-OA nanoparticles (PAS-AONs).

Novel pH-Responsive Structural Rearrangement of Myristic Acid-Conjugated Quetiapine Nanosuspension for Enhanced Long-Acting Delivery Performance.

Quetiapine myristate (QM), an ester-bonded lipophilic prodrug of quetiapine (QTP), is synthesized and converted into an amphiphilic structure in acidic pH to trigger a novel self-assembled QM nanosuspension (QMN). Following injection, this QMN rearranges within physiological pH to form nanoaggregates in structure, resulting in enhanced physicochemical properties and in vivo therapeutic performance without an initial burst release. The 200-nm-sized QMN exhibits less invasive injection, higher drug content, and better storage stability profile than conventional poly(lactide-co-glycolide) (PLGA) nanosuspensions containing QTP or QM.