Targeting pentamidine towards CD44-overexpressing cells using hyaluronated lipid-polymer hybrid nanoparticles.

Biodegradable nanocarriers possess enormous potential for use as drug delivery systems that can accomplish controlled and targeted drug release, and a wide range of nanosystems have been reported for the treatment and/or diagnosis of various diseases and disorders. Of the various nanocarriers currently available, liposomes and polymer nanoparticles have been extensively studied and some formulations have already reached the market. However, a combination of properties to create a single hybrid system can give these carriers significant advantages, such as improvement in encapsulation efficacy, higher stability, and active targeting towards specific cells or tissues, over lipid or polymer-based platforms. To this aim, this work presents the formulation of poly(lactic-co-glycolic) acid (PLGA) nanoparticles in the presence of a hyaluronic acid (HA)-phospholipid conjugate (HA-DPPE), which was used to anchor HA onto the nanoparticle surface and therefore create an actively targeted hybrid nanosystem. Furthermore, ionic interactions have been proposed for drug encapsulation, leading us to select the free base form of pentamidine (PTM-B) as the model drug. We herein report the preparation of hybrid nanocarriers that were loaded via ion-pairing between the negatively charged PLGA and HA and the positively charged PTM-B, demonstrating an improved loading capacity compared to PLGA-based nanoparticles. The nanocarriers displayed a size of below 150 nm, a negative zeta potential of -35 mV, a core-shell internal arrangement and high encapsulation efficiency (90%). Finally, the ability to be taken up and exert preferential and receptor-mediated cytotoxicity on cancer cells that overexpress the HA specific receptor (CD44) has been evaluated. Competition assays supported the hypothesis that PLGA/HA-DPPE nanoparticles deliver their cargo within cells in a CD44-dependent manner.

Phenolation of cyclodextrin polymers controls their lead and organic micropollutant adsorption.

Porous ß-cyclodextrin polymers linked with tetrafluoroterephthalonitrile (TFN-CDPs) have shown promise for adsorbing organic micropollutants (MPs) more quickly and effectively than conventional adsorbents. Prior to their discovery, the nucleophilic aromatic substitution (SNAr) reaction used to prepare TFN-CDP was nearly unknown for the aliphatic alcohol nucleophiles, and the low isolated yields of TFN-CDP motivated model studies of the reaction between TFN and n-butanol. These experiments reveal a previously undescribed substitution reaction of TFN in which a fluorine is substituted by a hydroxyl group. This process is responsible for the low yields of the polymerization and incorporates phenolate groups into the polymer network. Phenolation and polymerization (etherification) are competing processes, and the level of phenolate incorporation was controlled by varying the rate of base addition and initial monomer concentrations. TFN-CDPs with varying phenolate content were prepared and evaluated as adsorbents for both Pb2+ ions and 83 MPs. More heavily phenolated polymers showed increased capacity to bind Pb2+ ions. Phenolation was also correlated with increased binding affinity for almost all of the 83 MPs tested, including neutral, cationic, and anionic substances. These results leverage a newly discovered side reaction during SNAr reactions of electron-poor aryl fluorides to improve both the yield and the uptake affinity for both lead and organic MPs of TFN-CDPs.