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Haniye Najafi,Ali Mohammad Tamaddon,Samira Sadat Abolmaali,Bahareh Owrangi,Younes Ghasemi 한국고분자학회 2015 Macromolecular Research Vol.23 No.7
To improve transfection of plasmid DNA as well as serum protein stability of polyionic complex nanoparticles of branched polyethyleneimine (bPEI), poly(ethylene glycol) (PEG)-stabilized nanoparticles were made from L-histidine substituted bPEI (PEI-Histidine) synthesized by Fmoc chemistry. The polymer was characterized by TNBS assay, 1H NMR, GFC, potentiometric titration and elemental analysis of carbon and nitrogen, DNA condensation, and the stability against extracellular matrix (heparin sulfate) was investigated by dye exclusion and agarose gel retardation assays. The nanoparticles were characterized by dynamic light scattering-zeta potential analyzer. Cytotoxicity and expression of enhanced green fluorescent protein (EGFP) were determined in hepatocellular carcinoma by MTT assay and fluorescent techniques. PEI-Histidine showed a reduced pKa without any significant loss of total primary amines. Plasmid DNA was condensed almost thoroughly with PEGylated polymers, either bPEI or PEI-Histidine, at lower critical N/P ratios. PEGylated PEI-Histidine showed the better resistance to heparin induced displacement and the lower cytotoxicity when it was compared to bPEI. Interestingly unlike bPEI, smaller and less positively charged nanoparticles were obtained from PEGylated PEI-Histidine at N/P ratio=2 that resulted in about 4 folds higher EGFP expression than bPEI without any significant cytotoxicity. These properties are consistent with the higher serum protein resistance and buffer capacity of PEGylated PEI-Histidine at endosomal acidic pH.
Vahid Alimardani,Samira Sadat Abolmaali,Gholamhossein Yousefi,Mohammad Hossein Nowroozzadeh,Ali Mohammad Tamaddon 한국공업화학회 2023 Journal of Industrial and Engineering Chemistry Vol.119 No.-
Dissolving microneedles (dMNs) are proving to be attractive minimally invasive ophthalmic delivery systemsowing to their superior ability to deliver a variety of therapeutic agents through the cornea or sclera. Nevertheless, dMN formulation is most often complicated when poorly water-soluble drugs are used,because dMNs usually contain water-soluble polymers that dissolve quickly in ocular tissues. Here, wesynthesized the thermosensitive in-situ micelle-forming poly (N-isopropyl acrylamide)-b-poly (lglutamicacid) (PNIPAAm-b-PGA) copolymer which was soluble in organic and aqueous solvents, makingit possible to prepare MNs containing hydrophilic drugs. After full characterization of the copolymer, itwas successfully used to fabricate dMNs using the micro-molding technique. Remarkably, they generatedin-situ nanomicelles (NMCs) with sizes below 100 nm allowing for efficient dexamethasone (DEX) encapsulation. In this regard, the concentration of PNIPAAm-b-PGA copolymer was optimized to producemicroneedles with acceptable properties. A series of characteristics were assessed for microneedles,including mechanical and insertion properties, drug loading, in vitro release behavior, and in vitro permeation. Overall, the findings indicated that poly PNIPAAm-b-PGA copolymer is capable of self-assemblinginto NMCs and can significantly incorporate DEX as a hydrophobic drug, improving the trans-scleral DEX)permeation across the sclera, making it a promising system for treating posterior ocular diseases.