Melt-Extruded Paclitaxel Nanocrystal-Loaded Sutures for Sustained Local Drug Delivery
摘要
To develop biodegradable poly(lactic‑co‑glycolic acid) (PLGA) sutures loaded with paclitaxel (PTX) nanocrystals for sustained local drug delivery and to systematically evaluate their physicochemical, mechanical, and drug‑release properties.
MethodsPTX nanocrystals were prepared via wet media milling, yielding particles with a Z‑average size of 278.33 nm and a polydispersity index of 0.207. The nanocrystals were incorporated into PLGA sutures using a solvent‑free melt extrusion process followed by fiber drawing. Scanning electron microscopy was used to assess nanocrystal dispersion and fiber morphology, while wide‑angle X‑ray scattering evaluated PTX crystallinity and crystal orientation within the fibers. Mechanical properties were characterized by tensile testing. In vitro studies were conducted to assess fi ber shrinkage and PTX release behavior.
ResultsScanning electron microscopy confirmed homogeneous dispersion of PTX nanocrystals throughout the PLGA matrix, and wide‑angle X‑ray scattering demonstrated retention of PTX crystallinity with partial crystal orientation induced by fiber drawing. Molecular alignment of PLGA chains during stretching significantly enhanced mechanical performance, with stretched fibers exhibiting a tensile strength of 78.70 ± 11.50 MPa compared to 59.60 ± 2.50 MPa for unstretched polymer rods. Substantial fiber shrinkage was observed during in vitro studies; however, incorporation of PEG 8000 reduced shrinkage from 62% to 24%, but also reduced tensile strength to 40.33 ± 6.00 MPa. Drug‑release studies revealed a biphasic profile characterized by an initial lag phase followed by sustained PTX release, reaching approximately 60% cumulative release over 63 days.
ConclusionThese findings support the feasibility of melt‑extruded, drug‑loaded PLGA sutures as a platform for sustained local drug delivery.
Graphical Abstract