Preparation of Effective and Safe Gene Carriers by Grafting Alkyl Chains to Generation 5 Polypropyleneimine
Journal Title: AAPS PharmSciTech - Year 2015, Vol 16, Issue 5
Abstract
Gene therapy is a novel method to treat a variety of diseases including genetic disorders and cancer. Nonviral gene carriers have now gained considerable attention as gene carrier systems. Polyamidoamine (PAMAM) and polypropyleneimine (PPI) are the two most widely used denderimers in gene delivery studies. The aim of the current study was to investigate the effects of modification of generation 5 polypropyleneimine (G5 PPI) dendrimers with alkanoate groups as hydrophobic moieties on DNA transfection and cytotoxicity. Six, 10, and 16 carbon derivatives of bromoalkanoic acids were conjugated onto PPI with 10%, 30%, and 50% of surface amine grafting. Ethidium bromide exclusion assay results proved the ability of modified carriers to condense DNA. Transfection assay showed higher DNA delivery potential for 30% and 50% grafting with decanoate moieties compared to native G5 PPI and SuperfectTM. 3-(4,5-Dimethylthiazol-2-yl)-2,5-di phenyltetrazolium bromide (MTT) and apoptosis experiments showed lower toxicity for modified carriers compared to unmodified PPI. The hemolytic effect of grafted carriers was not significantly different from G5 PPI. Size and zeta potential measurements revealed that polyplex size was less than 200 nm and electrical charges were in the range 14–25 mV. The hydrophobic modifications improved transfection activity and toxicity of G5 PPI without negatively affecting hemocompatibility. These modified carriers are therefore promising candidates for further in vivo investigations.
Authors and Affiliations
Maryam Hashemi, Hamideh Parhiz, Ahad Mokhtarzadeh, Seyed Meghdad Tabatabai, Sara Amel Farzad, Haniyeh Rezagholizadeh Shirvan, Mohammad Ramezani
Keywords
Related Articles
- EP ID EP682276
- DOI 10.1208/s12249-015-0284-2
- Views 91
- Downloads 0
A Short Term Quality Control Tool for Biodegradable Microspheres
Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches...
Proniosomal Oral Tablets for Controlled Delivery and Enhanced Pharmacokinetic Properties of Acemetacin
Free-flowing proniosomal powders of acemetacin (AC) were prepared using the slurry method and maltodextrin as carrier. Positively charged proniosomes composed of 70:20:10 of Span 60/cholesterol (Chol)/stearylamine (SA),...
A Novel Oral Preparation of Hydroxysafflor Yellow A Base on a Chitosan Complex: A Strategy to Enhance the Oral Bioavailability
Hydroxysafflor yellow A (HSYA), the main active pharmaceutical ingredient of the safflower plant (Carthamus tinctorius L.), is a hydrophilic drug with low oral bioavailability (BA). The objective of the present study was...
Development and Evaluation of Diclofenac Sodium Loaded-N-Trimethyl Chitosan Nanoparticles for Ophthalmic Use
The ophthalmic preparation of diclofenac sodium (DC) for relieving ocular inflammation is presently available in the market only as an eye drop solution. Due to its low occular bioavailability, it requires frequent appli...
Application of Quality by Design (QbD) Approach to Ultrasonic Atomization Spray Coating of Drug-Eluting Stents
The drug coating process for coated drug-eluting stents (DES) has been identified as a key source of inter- and intra-batch variability in drug elution rates. Quality-by-design (QbD) principles were applied to gain an un...