flash-nanoprecipitation-for-encapsulation-hydrophobic-hydrophilic

Flash NanoPrecipitation for the Encapsulation of Hydrophobic and Hydrophilic Compounds in Polymeric Nanoparticles

The formulation of a therapeutic compound into nanoparticles (NPs) can impart unique properties. For poorly water-soluble drugs, NP formulations can ...

synthesizing-lipid-nanoparticles-turbulent-flow-confined-impinging

Synthesizing Lipid Nanoparticles by Turbulent Flow in Confined Impinging Jet Mixers

Lipid nanoparticles (LNPs) have demonstrated their enormous potential as therapeutic delivery vehicles, as evidenced by the approval and global usage of ...

Princeton University

Dense fluorescent pigments used for inkjet printing of UV and IR-readable non-photobleaching security features require stabilizers to prevent aggregation/sedimentation and inkjet head clogging at high resolution. A study of small molecule adsorption to α-alumina, a model system for security pigments, is presented. Alumina is dispersed by two methods yielding different zeta potentials but identical isoelectric points. Essentially complete dispersion is obtained in water at pH 3 but aggregation occurs at pH 6 where the surface charging is lower. Adsorption studies focus on the naphthyl-phosphate, -sulfate, and hydroxyl (triethylene glycol) groups. Phosphate adsorption was strongest with a 1.2 molecules/nm plateau, close to the titratable exchange capacity of 1.3 OH groups/nm on the alumina surface with ΔH=-7.58±1.63kJ/mol determined by calorimetry. Sulfate adsorption was weaker with a more linear adsorption isotherm. The adsorption/exchange process yields a rise in pH that is correlated with the binding strength. Hydroxyl binding is weakest, being driven by hydrogen bonding, and showed no rise in pH during adsorption. A polyphosphate-poly(ethylene glycol) block copolymer is expected to be advantageous for the dispersion of such inkjet colloids.

Adsorption characteristics of charged and nonionic small molecules to colloidal alumina.

Pseudomonas aeruginosa is an opportunistic gram-negative pathogen that causes a wide range of infections; it is becoming increasingly difficult to treat due to antibiotic resistance. Quorum-sensing (QS) based therapeutics, which function by disabling pathogen virulence without killing pathogens, are a promising class of drugs that may be used to treat bacterial infections without eliciting resistance development. The use of QS drugs to treat pulmonary P. aeruginosa infections, however, has been greatly limited due to the inability to deliver QS drugs at sufficiently high concentrations past physiological barriers such as pulmonary mucus. Here we apply a block copolymer-directed self-assembly process, Flash NanoPrecipitation, to develop a series of QS-active formulations that are fully water dispersible, stable, and mucus-penetrating. These formulations inhibit P. aeruginosa virulence without inhibiting cell growth. Particle size (70 nm-400 nm) and release rate (1 h-14 days) can be tuned by altering constructs' physical properties and formulation excipients. We also demonstrate, to the best of our knowledge, the first instance of a QS nanocarrier platform technology that can penetrate through human cystic fibrosis pulmonary mucus. This work highlights the need to incorporate nanoformulation strategies into the development of next-generation antimicrobial therapeutics.

Pseudomonas aeruginosa pyocyanin production reduced by quorum-sensing inhibiting nanocarriers.

Flash NanoPrecipitation is a scalable approach to generate polymeric nanoparticles using rapid micromixing in specially designed geometries such as a confined impinging jets mixer or a Multi-Inlet Vortex Mixer (MIVM). A major limitation of formulation screening using the MIVM is that a single run requires tens of milligrams of the therapeutic. To overcome this, we have developed a scaled-down version of the MIVM, requiring as little as 0.2 mg of therapeutic, for formulation screening. The redesigned mixer can then be attached to pumps for scale-up of the identified formulation. It was shown that Reynolds number allowed accurate scaling between the 2 MIVM designs. The utility of the small-scale MIVM for formulation development was demonstrated through the encapsulation of a number of hydrophilic macromolecules using inverse Flash NanoPrecipitation with target loadings as high as 50% by mass.

Design of a Small-Scale Multi-Inlet Vortex Mixer for Scalable Nanoparticle Production and Application to the Encapsulation of Biologics by Inverse Flash NanoPrecipitation.

ArticleTotal : 2	Year
Publication title Cited by 72	2019
Publication title Cited by 20	2024

Article	Year
Adsorption characteristics of charged and nonionic small molecules to colloidal alumina. Journal of colloid and interface science\| PubMed ID: 29054004	2018
Pseudomonas aeruginosa pyocyanin production reduced by quorum-sensing inhibiting nanocarriers. International journal of pharmaceutics\| PubMed ID: 29608955	2018
Design of a Small-Scale Multi-Inlet Vortex Mixer for Scalable Nanoparticle Production and Application to the Encapsulation of Biologics by Inverse Flash NanoPrecipitation. Journal of pharmaceutical sciences\| PubMed ID: 29772223	2018

Robert K. Prud'homme

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