Influence of chitosan-tripolyphosphate nanoparticles on thermosensitive polymeric hydrogels: structural organization, drug release mechanisms and cytotoxicity

Chitosan-tripolyphosphate (CS-TPP) nanoparticles containing naproxen (NPX) were dispersed in poloxamer (PL) as unique (PL407) or binary (PL407-PL403) systems. Nanoparticles presented diameter of ∼250 nm and zeta potential of ∼35 mV with drug loading and encapsulation efficiency of 98.4 ± 0.3% and 36.9 ± 0.12%, respectively. NPX-CS-TPP shifted the sol-gel transition and micellization temperatures. PL407-PL403 systems presented G′ > G″ compared to PL407. SAXS patterns revealed transitions from lamellar to hexagonal phase organizations with low drug release rates, in the presence of CS-TPP nanoparticles. NPX-CS-TPP-PL407 induced lower cytotoxicity compared to PL407-PL403 in fibroblasts and osteoblasts, making them promising systems for intra-articular delivery.