Thermogel Loaded with Low-Dose Paclitaxel as a Facile Coating to Alleviate Periprosthetic Fibrous Capsule Formation

Abstract

Medical-grade silicones as implants have been utilized for decades. However, the postoperative complications, such as capsular formation and contracture, have not yet been fully controlled and resolved. The aim of the present study is to elucidate whether the capsular formation can be alleviated by local and sustained delivery of low-dose paclitaxel (PTX) during the critical phase after the insertion of silicone implants. A biocompatible and thermogelling poly(lactic acid- co-glycolic acid)- b-poly(ethylene glycol)- b-poly(lactic acid- co-glycolic acid) triblock copolymer was synthesized by us. The micelles formed by the amphiphilic polymers in water could act as a reservoir for the solubilization of PTX, a very hydrophobic drug. The concentrated polymer aqueous solution containing PTX exhibited a sol-gel transition upon heating and formed a thermogel depot at body temperature. In vitro release tests demonstrated that the entrapped microgram-level PTX displayed a sustained release manner up to 57 days without a significant initial burst effect. Customized silicone implants coated with the PTX-loaded thermogels at various drug concentrations were inserted into the pockets of the subpanniculus carnosus plane of rats. The histological observations performed 1 month postoperation showed that the sustained release of PTX with an appropriate dose significantly reduced the peri-implant capsule thickness, production and deposition of collagen, and expression of contracture-mediating factors compared with bare silicone implants. More importantly, such an optimum dose had an excellent repeatability for the suppression of the capsular formation. Therefore, this study provides a strategic foothold regarding the sustained release of low-dose PTX to alleviate fibrotic capsule formation after implantation, and the microgram-level PTX-loaded thermogel holds great potential as an "all-purpose antifibrosis coating" for veiling the surfaces of various implantable medical devices.

Visualizing the In Vivo Evolution of an Injectable and Thermosensitive Hydrogel Using Tri‐Modal Bioimaging

“…In rheology, the temperature, where the G ′ increases to and over the G ′′, is defined as the T gel . [ 15 ] The T gel confirmed via the dynamic rheological measurement was very close to that obtained from the vial‐inverting method. The MNPs@RBGel system exhibited similar change curves of moduli upon heating, indicating that the chemical modification of RB fragment plus the loading of MNPs did not significantly impact the temperature‐induced sol–gel transition behaviors of the polymer hydrogel.…”

Injectable hydrogels for the sustained delivery of a HER2-targeted antibody for preventing local relapse of HER2+ breast cancer after breast-conserving surgery

“…Sharp increases in both G ′ and G ′′ were observed at a certain temperature, and the level of the increase in G ′ was greater than the level of the increase in G ′′, which indicated the occurrence of in situ gelation. Generally, when the G ′ is equal to the G ′′ in rheology, the corresponding temperature is defined as T g 54. The T g s, which were very close to those confirmed by the vial-inverting approach, were found to be 24 and 31 °C for mixture-A and mixture-B, respectively.…”

4D Printed Hydrogels: Fabrication, Materials, and Applications

“…The crosslinks can be chemical (covalent bonding) or physical (such as van der Waals forces, electrostatic interactions, and hydrogen bonds), enabling the structural integrity of the hydrogel networks to be maintained with significant water content. [ 33,34 ] Compared with conventional polymer materials, hydrogels have the unique advantage of softness, biocompatibility, and multifunctionality due to their large water content, [ 35 ] resulting in wide biomedical applications such as drug delivery systems, [ 36,37 ] implants, [ 38 ] contact lenses, [ 39 ] cellular scaffolds, [ 40 ] and cell cultures. [ 41 ] The stimuli‐responsive hydrogel is a unique type of hydrogel having the ability to sense changes in temperature, pH, light, or other environmental factors, exhibiting responses via changing shape, color, mechanical properties, or biological properties.…”