Rational Mitomycin Nanocarriers Based on Hydrophobically Functionalized Polyelectrolytes and Poly(lactide-co-glycolide)

Abstract

Encapsulation of hydrophilic and amphiphilic drugs in appropriate colloidal carrier systems for sustained release is an emerging problem. In general, hydrophobic bioactive substances tend to accumulate in water-immiscible polymeric domains, and the release process is controlled by their low aqueous solubility and limited diffusion from the nanocarrier matrix. Conversely, hydrophilic/amphiphilic drugs are typically water-soluble and insoluble in numerous polymers. Therefore, a core–shell approach—nanocarriers comprising an internal core and external shell microenvironments of different properties—can be exploited for hydrophilic/amphiphilic drugs. To produce colloidally stable poly(lactic- co -glycolic) (PLGA) nanoparticles for mitomycin C (MMC) delivery and controlled release, a unique class of amphiphilic polymers—hydrophobically functionalized polyelectrolytes—were utilized as shell-forming materials, comprising both stabilization via electrostatic repulsive forces and anchoring to the core via hydrophobic interactions. Undoubtedly, the use of these polymeric building blocks for the core–shell approach contributes to the enhancement of the payload chemical stability and sustained release profiles. The studied nanoparticles were prepared via nanoprecipitation of the PLGA polymer and were dissolved in acetone as a good solvent and in an aqueous solution containing hydrophobically functionalized poly(4-styrenesulfonic- co -maleic acid) and poly(acrylic acid) of differing hydrophilic–lipophilic balance values. The type of the hydrophobically functionalized polyelectrolyte (HF-PE) was crucial for the chemical stability of the payload—derivatives of poly(acrylic acid) were found to cause very rapid degradation (hydrolysis) of MMC, in contrast to poly(4-styrenesulfonic- co -maleic acid). The present contribution allowed us to gain crucial information about novel colloidal nanocarrier systems for MMC delivery, especially in the fields of optimal HF-PE concentrations, appropriate core and shell building materials, and the colloidal and chemical stability of the system.

Regulation of Immune Inflammation and Promotion of Periodontal Bone Regeneration by Irisin-Loaded Bioactive Glass Nanoparticles

“…Bioactive materials including bioactive glasses, hydrogels, bioceramics, and biopolymers have been increasingly used in the medical field as biological substitutes to help achieving the reconstruction, maintenance, and improvement of damaged tissues. , Hydrogels are widely used as ideal materials for articular cartilage repair due to high water content . Bioceramics are biologically active and mechanically strong materials, including ceramic composites, amorphous glasses, and crystalline ceramics. , However, the hardness and brittleness of bioceramics are so high that they might exhibit undesirable degradation/resorption rates .…”

Lipase-Responsive Lignin Composite Nanoparticles for the Delivery of Insoluble Bioactives

“…4 An encapsulated delivery system offers a promising solution to address these issues. 5 It not only safeguards the active substances, enhancing their stability, but also improves the aqueous solubility of insoluble compounds and enables targeted and controlled release, thereby enhancing bioavailability. 1,6,7 Carotenoids, which are biologically active substances, find wide applications as coloring agents in food, cosmetics, and feed.…”

“…The poor solubility and chemical stability of insoluble bioactives pose challenges, which is also a major obstacle to improving bioavailability . An encapsulated delivery system offers a promising solution to address these issues . It not only safeguards the active substances, enhancing their stability, but also improves the aqueous solubility of insoluble compounds and enables targeted and controlled release, thereby enhancing bioavailability. ,, …”

Effect of Temperature and Composition on the Loading of Curcumin into PLGA/PLLA Core–Shell Nanoparticles Stabilized by Hydrophobically Functionalized Polyelectrolytes

“…16−19 On the other hand, ionic compounds adsorbed at the nanocarrier surface provide the formation of an electrically charged layer, stabilizing the material by electrostatic repulsive forces. 8,12,16,20 The aforementioned ionic compounds most often include surfactants and polyelectrolyte molecules, which have a high tendency to adsorb at interfaces due to their amphiphilic character. 16 Sometimes polyelectrolytes may be additionally modified, e.g., by coupling with hydrophobic compounds, to assume sufficient anchoring to hydrophobic surfaces.…”

“…16 Sometimes polyelectrolytes may be additionally modified, e.g., by coupling with hydrophobic compounds, to assume sufficient anchoring to hydrophobic surfaces. 12,20 These types of modified polyanions and polycations are known as hydrophobically functionalized polyelectrolytes (HF-PEs) when nonpolar side groups are grafted to the charged backbone. 21,22 It should be noted that electrostatic repulsion stabilization may be expressed quantitatively by the ζ-potential of colloidal nanoparticles; negative or positive values of this parameter, below −30 mV or above 30 mV, respectively, are considered to provide stability against coalescence.…”