The main problem with oral drug delivery using gelatin is rapid dissolution in aqueous mediums, which results in high-speed drug release. In the present study to overcome the challenge, we used glutaraldehyde to cross-link gelatin in order to control the burst release of drug. A drug delivery system based on gelatin nanoparticles (GNPs) for carrying Gliclazide was prepared by a two-step dissolution method. FTIR spectrum showed the presence of an aldimine functional group in GNPs, which confirms that gelatin structure is cross-linked by glutaraldehyde. XRD pattern showed that the crystallinity and crystal size of GNPs were 8% and 73 nm, respectively. SEM images showed the cross-linked structure of GNPs by glutaraldehyde, and DLS analysis exhibited an average particle size of about 88 nm. Ninhydrin assay showed the GNPs completely cross-linked for all ratios of gelatin to cross-linker (8%v/v, 16%v/v, and 25%v/v). After 8 h, the highest and lowest swelling percentages were related to cross-linked samples with 8%v/v and 25%v/v glutaraldehyde (in PBS buffer, pH=7.4, and 37 °C), respectively. The nanoparticle yield and drug loading were optimized via cross-linker concentration and GNPs: GLI ratio. The drug-release behavior from GNPs was controlled by the degree of swelling. The results showed that cross-linked GNPs via 8 %v/v and 25%v/v glutaraldehyde had the highest and lowest GLI release, (70% and 34% after 480 min, respectively, in PBS buffer, pH=7.4, and 37 °C). GLI release from GNPs showed controlled behavior compared with commercial anti-diabetic drugs, including Diabezide 80 mg and Diamicron MR 30 mg. MTT assay results showed that 94.5% of cells in contact with GLI-loaded GNPs survived.
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