Gelatin Nanoparticles for Targeted Dual Drug Release out of Alginate-di-Aldehyde-Gelatin Gels

Abstract

The aim of the present work was to develop a dual staged drug release of an antibiotic (clindamycin) and a growth factor: bone morphogenetic protein-2 (BMP-2) from a biodegradable system consisting of hydrogel and gelatin nanoparticles (GNP). Two-step de-solvation allowed us to prepare GNPs (~100 nm) as drug carriers. Fluorescein isothiocyanate (FITC)-conjugated protein A was used as a model substance for BMP-2. A 28-day release experiment was performed to determine the release kinetics from GNP for both FITC-protein A and BMP-2, and for clindamycin (CLI) from the hydrogel. The size, structure, and overall morphology of GNP samples (empty, loaded with FITC-protein A and BMP-2) were examined using an environmental scanning electron microscope (ESEM). Cell culture assays (Live/dead; cell proliferation; cytotoxicity) were performed with MG-63 cells and BMP-2-loaded GNPs. Drug release experiments using clindamycin-loaded alginate-di-aldehyde (ADA) gelatin gels containing the drug-loaded GNPs were performed for 28 days. The resulting GNPs showed an empty size of 117 ± 29 nm, 176 ± 15 nm and 216 ± 36 nm when containing 2% FITC-protein A and 1% BMP-2, respectively. No negative effects of BMP-2-loaded GNPs on MG-63 cells were observed in live/dead staining. In the proliferation assay, an increase in cell proliferation was observed for both GNPs (GNP + BMP-2 and controls). The cytotoxicity assay continuously showed very low cytotoxicity for GNPs (empty; loaded). Clindamycin release showed a concentration of 25-fold higher than the minimum inhibitory concentration (MIC) against Staphylococcus aureus throughout the 28 day period. BMP-2 showed a reduced burst release and a steady release (~2 µg/mL) over a 28 day period.

Dual release of daptomycin and BMP-2 from a composite of β-TCP ceramic and ADA gelatin

“…Comparatively, ADA gelatin gel has exhibited superior mechanical properties when incorporated into β-TCP ceramic and demonstrated higher biodegradability than pure alginate [ 32 ]. Given its prior assessment for drug release [ 31 , 33 ], ADA gelatin gel emerges as a promising hydrogel for targeted and controlled drug delivery. Daptomycin, a relatively new antibiotic in the gram-positive spectrum, and BMP-2, a substance that promotes bone healing, are of interest for local application.…”

“…This can be done by dipping, dropping or spraying [26]. The literature has previously documented a delayed in vitro drug release from a carrier system [27], comprising microporous β-TCP ceramic and alginate [28][29][30][31]. Comparatively, ADA gelatin gel has exhibited superior mechanical properties when incorporated into β-TCP ceramic and demonstrated higher biodegradability than pure alginate [32].…”

Dual Release of Daptomycin and BMP-2 from a Composite of β-TCP Ceramic and ADA Gelatin for Bone Regeneration

“…This can be done by dipping, dropping or spraying [26]. The literature has previously documented a delayed in vitro drug release from a carrier system [27], comprising microporous β-TCP ceramic and alginate [28][29][30][31]. Comparatively, ADA gelatin gel has exhibited superior mechanical properties when incorporated into β-TCP ceramic and demonstrated higher biodegradability than pure alginate [32].…”

“…Comparatively, ADA gelatin gel has exhibited superior mechanical properties when incorporated into β-TCP ceramic and demonstrated higher biodegradability than pure alginate [32]. Given its prior assessment for drug release [31,33], ADA gelatin gel emerges as a promising hydrogel for targeted and controlled drug delivery. Notably, the potential for dual drug release in this system remains unexplored, representing an avenue for enhancing patient outcomes by combining anti-infective treatment, bone growth promotion therapy, and improved bone stability facilitated by the β-TCP ceramic.…”

Special Issue: Bioceramics, Bioglasses, and Gels for Tissue Engineering

“…Another review article [33] discussed soft tissue repair using nanoparticle-modified biocompatible polymers including hydrogels. Schrade S et al [34] found that gelatin nanoparticles can be used for targeted dual drug release out of aleginate-di-aldehyde-gelatin gels. Calcium magnesium silicate (CaO-MgO-SiO 2 )-based bioceramics, containing bioactive phases of diopside, akermanite, and merwinite, were prepared by Alecu AE et al [35] using the solgel method followed by thermal treatment.…”