title: Microfluidic approach for highly efficient synthesis of heparin-based bioconjugates for drug delivery.
abstract: This paper demonstrates the highly efficient synthesis of amphiphilic heparin-folic acid-retinoic acid (HFR) bioconjugates with a high drug coupling ratio by a microfluidic approach. The microfluidic synthesis enabled the conjugation of 17 molecules of retinoic acid to each heparin chain with 21 possible groups for attachment after reacting for several minutes. In contrast, about 11 molecules of the drug were covalently conjugated to one heparin chain after 4 days in the bulk reaction. The microfluidic based-HFR bioconjugates readily self-assembled in aqueous media to form uniform nanoparticles, while the product from the bulk reaction formed non-uniform nanoparticles with broad size distribution. The HFR nanoparticles with high drug content effectively delivered the drug to folate receptor-positive cancer cells with superior cellular uptake and selective cytotoxicity in vitro compared to HFR nanoparticles synthesized in bulk reaction. With the ability to achieve high drug content in heparin carrier within a short reaction time, the microfluidic technique offers new alternatives for the efficient synthesis of polymer-based conjugates for drug delivery.
authors: Department of Applied Chemistry & Biological Engineering, Chungnam National University, 220 Gung-dong, Yuseong-gu, Daejeon 305-764, Korea.
authors: Thanh Huyen
authors: TH
authors: Tran
authors: Chi Thanh
authors: CT
authors: Nguyen
authors: Dong-Pyo
authors: DP
authors: Kim
authors: Yong-Kyu
authors: YK
authors: Lee
authors: Kang Moo
authors: KM
authors: Huh
mesh_terms: D019149:Bioreactors; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000096:biosynthesis; D006493:Heparin / Q000096:biosynthesis*; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000295:instrumentation / Q000379:methods*; D044085:Microfluidics / Q000295:instrumentation*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D014212:Tretinoin / Q000378:metabolism
chemical_list: D011108:Polymers; D014212:Tretinoin; D006493:Heparin; D005492:Folic Acid