Peer-reviewed Articles

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Bose,S., Phan,C.-M., Rizwan,M., Tse,J. W., Yim,E., Jones,L. Fabrication and Characterization of an Enzyme-Triggered, Therapeutic-Releasing Hydrogel Bandage Contact Lens Material Pharmaceutics 2024;16(1):Article 26 [ Show Abstract ]

Purpose: The purpose of this study was to develop an enzyme-triggered, therapeutic-releasing bandage contact lens material using a unique gelatin methacrylate formulation (GelMA+).

Methods: Two GelMA+ formulations, 20% w/v, and 30% w/v concentrations, were prepared through UV polymerization. The physical properties of the material, including porosity, tensile strain, and swelling ratio, were characterized. The enzymatic degradation of the material was assessed in the presence of matrix metalloproteinase-9 (MMP-9) at concentrations ranging from 0 to 300 µg/mL. Cell viability, cell growth, and cytotoxicity on the GelMA+ gels were evaluated using the AlamarBlueTM assay and the LIVE/DEADTM Viability/Cytotoxicity kit staining with immortalized human corneal epithelial cells over 5 days. For drug release analysis, the 30% w/v gels were loaded with 3 µg of bovine lactoferrin (BLF) as a model drug, and its release was examined over 5 days under various MMP-9 concentrations.

Results: The 30% w/v GelMA+ demonstrated higher crosslinking density, increased tensile strength, smaller pore size, and lower swelling ratio (p < 0.05). In contrast, the 20% w/v GelMA+ degraded at a significantly faster rate (p < 0.001), reaching almost complete degradation within 48 h in the presence of 300 µg/mL of MMP-9. No signs of cytotoxic effects were observed in the live/dead staining assay for either concentration after 5 days. However, the 30% w/v GelMA+ exhibited significantly higher cell viability (p < 0.05). The 30% w/v GelMA+ demonstrated sustained release of the BLF over 5 days. The release rate of BLF increased significantly with higher concentrations of MMP-9 (p < 0.001), corresponding to the degradation rate of the gels.

Discussion: The release of BLF from GelMA+ gels was driven by a combination of diffusion and degradation of the material by MMP-9 enzymes. This work demonstrated that a GelMA+-based material that releases a therapeutic agent can be triggered by enzymes found in the tear fluid.

Wu,T.-Y., Huang,C.-C., Tsai,H.C., Lon,T.-K., Chen,P.-Y., Darge,H. F., Hong,Z.-X., Ham,H.-J., Lin,S.-Z., Lai,J.-Y., Chen,Y.-S. Mucin-mediated mucosal retention via end-terminal modified Pluronic F127-based hydrogel to increase drug accumulation in the lungs Biomaterials Advances 2024;Jan(156):213722 [ Show Abstract ]

Noninvasive lung drug delivery is critical for treating respiratory diseases. Pluronic-based copolymers have been used as multifunctional materials for medical and biological applications. However, the Pluronic F127-based hydrogel is rapidly degraded, adversely affecting the mechanical stability for prolonged drug release. Therefore, this study designed two thermosensitive copolymers by modifying the Pluronic F127 terminal groups with carboxyl (ADF127) or amine groups (EDF127) to improve the viscosity and storage modulus of drug formulations. β-alanine and ethylenediamine were conjugated at the terminal of Pluronic F127 using a two-step acetylation process, and the final copolymers were characterized using 1H nuclear magnetic resonance (1H NMR) and Fourier-transform infrared spectra. According to the 1H NMR spectra, Pluronic F127 was functionalized to form ADF127 and EDF127 with 85 % and 71 % functionalization degrees, respectively. Rheological studies revealed that the ADF127 (15 wt%) and EDF127 (15 wt%) viscosities increased from 1480 Pa.s (Pluronic F127) to 1700 Pa.s and 1800 Pa.s, respectively. Furthermore, the elastic modulus of ADF127 and EDF127 increased, compared with that of native Pluronic F127 with the addition of 5 % mucin, particularly for ADF127, thereby signifying the stronger adhesive nature of ADF127 and EDF127 with mucin. Additionally, ADF127 and EDF127 exhibited a decreased gelation temperature, decreasing from 33 °C (Pluronic F127 at 15 wt%) to 24 °C. Notably, the in vitro ADF127 and EDF127 drug release was prolonged (95 %; 48 h) by the hydrogel encapsulation of the liposome-Bdph combined with mucin, and the intermolecular hydrogen bonding between the mucin and the hydrogel increased the retention time and stiffness of the hydrogels. Furthermore, ADF127 and EDF127 incubated with NIH-3T3 cells exhibited biocompatibility within 2 mg/mL, compared with Pluronic F127. The nasal administration method was used to examine the biodistribution of the modified hydrogel carrying liposomes or exosomes with fluorescence using the IVIS system. Drug accumulation in the lungs decreased in the following order: ADF127 > EDF127 > liposomes or exosomes alone. These results indicated that the carboxyl group-modified Pluronic F127 enabled well-distributed drug accumulation in the lungs, which is beneficial for intranasal administration routes in treating diseases such as lung fibrosis.