Design and Characterization of Surface‐Crosslinked Gelatin Nanoparticles for the Delivery of Hydrophilic Macromolecular Drugs

Abstract

For nanotechnology enabled delivery of hydrophilic protein‐based drugs, several polymer‐based carrier systems have been used in the past to protect the sensitive load and to facilitate cellular uptake and crossing of biological barriers. This study uses gelatin, a natural and biodegradable macromolecule, as carrier material which is approved for several applications. Nanoprecipitation is used to form nanoparticles and to maintain the physicochemical integrity of gelatin, hydrophilic crosslinkers, e.g., paraformaldehyde, glutaraldehyde, carbodiimide, and transglutaminase are employed. However, these crosslinkers diffuse homogenously into the carrier matrix also crosslinking the polymeric matrix with the entrapped protein‐based molecules thus rendering it inactive. Hence a hydrophobic zero‐length crosslinker, diisopropylcarbodiimide, is applied to avoid diffusion into the particles. This will provide an opportunity to encapsulate protein‐based drugs in the non‐crosslinked matrix. The hypothesis of surface crosslinking is proven by the extent of crosslinking and more importantly by encapsulation and the release of lysozyme as a model hydrophilic protein. Furthermore, essential process parameters are evaluated such as crosslinker concentration, crosslinking time and crosslinking reaction temperature with regard to the effect on particle size, size distribution and zeta‐potential of gelatin nanoparticles. The optimum formulation results in the production of gelatin nanoparticles with 200‐300 nm and a polydispersity index < 0.2.

High-Density Horizontal Stacking of Chondrocytes via the Synergy of Biocompatible Magnetic Gelatin Nanocarriers and Internal Magnetic Navigation for Enhancing Cartilage Repair

“…MAGNCs were well-dispersed in aqueous solution, and no precipitates were observed, suggesting that hydrophobic SPIONs were cladded with hydrophilic AG. In comparison to SPIONs, MAGNCs were relatively stable in the water phase due to gelatin with a large portion of hydrophilic amino acids (lysine, serine, arginine, aspartic acid, and glutamic acid) [ 21 ]. According to several reports, the colloidal particle from the green synthesis using nature biomolecules such as fruits, vegetables, or plants provided the various nanoparticles with highly effective biofunctional performance and better cytocompatibility [ 22 , 23 , 24 , 25 ]; therefore, MAGNC synthesized from the AG would not affect the native morphology of chondrocytes.…”

Design of Gelatin-Capped Plasmonic-Diatomite Nanoparticles with Enhanced Galunisertib Loading Capacity for Drug Delivery Applications

“…The type B gelatin used in this study has an Isoelectric Point (IEP) between 4.8 and 5.4, therefore it was expected for AuDNPs-LY@Gel samples to have a negative surface charge in an aqueous solution pH 6.5–7.0 (pH ). However, a shift of the IEP of the gelatin toward 6–7 can be observed as a consequence of the crosslinking mechanism between COOH and NH 2 groups in the polymer backbone [ 32 ]. Due to this slight shift, the surface charge of AuDNP-LY@Gel samples was expected to be neutral at the IEP, or slightly positive.…”

Design of Polymeric and Biocompatible Delivery Systems by Dissolving Mesoporous Silica Templates

“…As proof-of-concept, we used purified green fluorescent protein (GFP) to create HC@GFP capsules. The protein was bioconjugated on the capsules as previously described [ 43 ], and was crosslinked using a 0.25% glutaraldehyde solution, a method commonly used in pharmaceutical technology ( Figure 3 ) [ 44 , 45 ]. Similar capsules were produced using bovine serum (FBS) as a sample of alternative protein.…”