Stabilization of Gelatin Nanoparticles Without Crosslinking

Khan, Saeed Ahmad; Schneider, Marc

doi:10.1002/mabi.201400214

Cited by 16 publications

(15 citation statements)

References 57 publications

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“…But, from formulation point of view, gelatin-based drug delivery systems cannot maintain their structural integrity upon exposure to aqueous environment thus disassembling and immediately releasing the incorporated payload. [34] Hence, it is important to stabilize these gelatin-based carrier systems in order to achieve physicochemical and mechanical stabilization in aqueous environment. Ever since the discovery of gelatin nano particles (GNPs) by Oppenheim et al, [35] crosslinking has been an indispensable step for the preparation of stable GNPs.…”

Section: Surface Crosslinkingmentioning

confidence: 99%

“…Therefore, a novel strategy for the stabilization of GNPs is needed. [34] In this study, we intend to crosslink GNPs only on the interface using hydrophobic zero-length crosslinkers in order to avoid the diffusion of crosslinker inside the nanoparticle matrix. To the best of our knowledge, the stabilization of GNPs with the application of hydrophobic zero-length crosslinkers is not reported so far.…”

Section: Surface Crosslinkingmentioning

confidence: 99%

“…The drug will not be released and might also be not active after crosslinking. Therefore, a novel strategy for the stabilization of GNPs is needed …”

Section: Introductionmentioning

confidence: 99%

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

Baseer

Koenneke

Zapp

et al. 2019

Macro Chemistry & Physics

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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.

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Section: Surface Crosslinkingmentioning

confidence: 99%

Section: Surface Crosslinkingmentioning

confidence: 99%

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

Baseer

Koenneke

Zapp

et al. 2019

Macro Chemistry & Physics

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“…(Although the term crosslinking can be used to describe different physico-chemical phenomena, in the present manuscript the term crosslinking is used to describe the formation of covalent chemical bonds among gelatin macromolecules with the mediation of smaller molecules, called crosslinking agents.) However, gelatin coating has also been proposed as an alternative to gelatin crosslinking [8] . Some of the most cited gelatin crosslinking agents are glutaraldehyde [9][10][11] , formaldehyde [1,12,13] , glyoxal [13,14] and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) [15,16] .…”

Section: Introductionmentioning

confidence: 99%

Preparation of gelatin beads treated with glucose and glycerol

2018

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ObstractGelatin is employed in pharmaceutical applications because of its biodegradability, biocompatibility and low toxicity. However, it may be necessary to promote gelatin crosslinking in order to develop drug release systems and extend release times. SEC analyses are used here for the first time to monitor the evolution of molar mass distributions of gelatins during treatment with glycerol and glucose in dispersed media. Unambiguous experimental evidence of gelatin crosslinking in presence of sugars and glycerol has yet to be presented. SEC results indicate that average molar masses decrease during gelatin treatment, while FT-IR analyses indicate that gelatins are subject to structural modifications during processing, which can explain the decrease of gelatin solubility after treatment. The results presented here indicate the importance of using SEC techniques to monitor gelatin crosslinking, as they seemingly contradict previously published results that make use of indirect measures for this purpose.

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“…NP formation is a complex phenomenon controlled by the polymer–antisolvent–solvent system. The diffusion and the affinity of the antisolvent to solvent and the polymer–solvent interactions influence the particle size . Among different organic solvents (acetone, acetonitrile, isopropanol, ethanol), only methanol was suitable for AuNC‐modified GNP formation.…”

Section: Resultsmentioning

confidence: 99%

NIR‐Emitting Gold Nanoclusters–Modified Gelatin Nanoparticles as a Bioimaging Agent in Tissue

El‐Sayed

Trouillet

Clasen

et al. 2019

Adv Healthcare Materials

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Gold nanocluster (AuNC) synthesis using a well‐distinguished polymer for nanoparticle‐mediated drug delivery paves the way for developing efficient theranostics based on pharmaceutically accepted materials. Gelatin‐stabilized AuNCs are synthesized and modified by glutathione for tuning the emission spectra. Addition of silver ions enhances the fluorescence, reaching also high quantum yield (26.7%). A simplified model can be proposed describing the nanoclusters' properties–structure relationship based on X‐ray photoelectron spectroscopy data and synthesis sequence. Furthermore, these modifications improve fluorescence stability toward pH changes and enzymatic degradation, offering different AuNCs for various applications. The impact of nanocluster formation on gelatin structure integrity is investigated by Fourier transform infrared spectrometry and matrix‐assisted laser desorption/ionization time of flight mass spectroscopy, being important to further formulate gelatin nanoparticles (GNPs). The 218 nm‐sized NPs show no cytotoxicity up to 600 µg mL−1 and are imaged in skin, as a challenging autofluorescent tissue, by confocal microscopy, when transcutaneously delivered using dissolving microneedles. Linear unmixing allows simultaneous imaging of AuNCs–GNPs and skin with accurate signal separation. This underlines the great potential for bioimaging of this system to better understand nanomaterials' behavior in tissue. Additionally, it is drug delivery system also potentially serving as a theranostic system.

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Stabilization of Gelatin Nanoparticles Without Crosslinking

Cited by 16 publications

References 57 publications

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

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

Preparation of gelatin beads treated with glucose and glycerol

NIR‐Emitting Gold Nanoclusters–Modified Gelatin Nanoparticles as a Bioimaging Agent in Tissue

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