Spray‐dried lipid‐hyaluronan‐polymethacrylate microparticles for drug delivery in the peritoneum

Abstract

Application of controlled release technology to the peritoneum would allow for sustained drug levels. However, some polymeric systems either create adhesions, or rapidly exit the peritoneum; neither result is desirable. Here we have produced particles based on sphyngomyelin, a phospholipid that occurs naturally in the peritoneum, along with hyaluronic acid and the polymethacrylate Eudragit E100 (to modulate drug release). Particles with a low proportion of E100 (5% (w/w); "high SPM") release albumin rapidly over 2 days, then more slowly; increasing the E100 to 20% (w/w; high "E100") slowed drug release markedly. When injected in the murine peritoneum, high SPM particles were disseminated as free particles, without forming collections. There was a mild inflammatory response but no formation of adhesions. High E100 particles formed collections in all animals, with an intense inflammatory response. Even so, there were very few adhesions. These results suggest that microparticulate formulations can be produced that have acceptable drug-releasing properties and are suitable for use in the peritoneum from the standpoint of biocompatibility.

Genipin-crosslinked gelatin microspheres as a strategy to prevent postsurgical peritoneal adhesions: In vitro and in vivo characterization

“…Furthermore, particle size will affect the spatial distribution in the abdominal cavity. Previous studies show that smaller microparticles are evenly distributed throughout the abdominal cavity whereas larger microparticles are mainly localized in the lower abdomen [16], [18], [20], [22]- [25] .…”

“…They can distribute throughout the entire peritoneal cavity. Due to their size, they can remain in the peritoneal cavity and locally provide an extended release of a drug, such as a chemotherapeutic agent [16], [18]- [21] . The size range of the microspheres is crucial as size determines the residence time in the peritoneal cavity.…”

Hyaluronic acid-based hydrogels: from a natural polysaccharide to complex networks

“…126 Because HA was not crosslinked in the particles, exposure to aqueous media can lead to the rapid dissolution of the particles. In fact, when preparing the particles via spray drying, HA is frequently mixed with other polymers (PEG 127 or Eudragit 128 ), lipid or surfactant molecules to stablize the particles and to modulate the drug release. Relatively well defined HA HGPs were prepared by reactive spray drying of a dilute HA-SH precursor solution containing sodium tetrathionate.…”

Microencapsulation of nanoparticles with enhanced drug loading for pH‐sensitive oral drug delivery for the treatment of colon cancer

“…When hydrophilic therapeutic agents are encapsulated into hydrophobic materials, there is a great repulsion between the two phases. It is challenging for hydrophilic drug to be encapsulated into hydrophobic material to form NPs 11, 12. Therefore, a variety of methods for improving the DL for drug‐delivery carriers have been developed by the modification of therapeutic drugs and encapsulation materials.…”

“…Some polymeric MSs have demonstrated a strong pH dependence; this means that they only take effect in environments of a certain pH value. Eudragit S100, an anionic polymer synthesized from methacrylic acid and methacrylic acid methyl ester, is a commonly used polymer for the fabrication of functionalized MSs 11. It is insoluble in acids and pure water and only dissolves in aqueous solution at pH 7 or higher;16, 17 this is ideal for colonic drug delivery.…”