title: Microfluidic Directed Synthesis of Alginate Nanogels with Tunable Pore Size for Efficient Protein Delivery.
abstract: Alginate is a biopolymer with favorable pH-sensitive properties for oral delivery of peptides and proteins. However, conventional alginate nanogels have limitations such as low encapsulation efficiency because of drug leaching during bead preparation and burst release in high pH values. These shortcomings originate from large pore size of the nanogels. In this work, we proposed an on-chip hydrodynamic flow focusing approach for synthesis of alginate nanogels with adjustable pore size to achieve fine-tunable release profile of the encapsulated bioactive agents. It is demonstrated that the microstructure of nanogels can be controlled through adjusting flow ratio and mixing time directed on microfluidic platforms consisting of cross-junction microchannels. In this study, the average pore size of alginate nanogels (i.e., average molecular weight between cross-links, Mc) was related to synthesis parameters. Mc was calculated from equations based on equilibrium swelling theory and proposed methods to modify the theory for pH-sensitive nanogels. In the equations we derived, size and compactness of nanogels are key factors, which can be adjusted by controlling the flow ratio. It was found that increase in flow ratio increases the size of nanogels and decreases their compactness. The size of on-chip generated nanogels for flow ratio of 0.02-0.2 was measured to be in the range of 68-138 nm. Moreover, a method based on the Mie theory was implemented to estimate the aggregation number (Nagg) of polymer chains inside the nanogels as an indicator of compactness. According to the size and compactness results along with equations of modified swelling theory, Mc obtained to be in the range of 0.5-0.8 kDa. The proposed method could be considered as a promising approach for efficient polypeptides encapsulation and their sustained release.
authors.affiliation: Department of Biomedical Engineering, Amirkabir University of Technology , Tehran, Iran.
authors.forename: Salime
authors.initials: S
authors.lastname: Bazban-Shotorbani
authors.affiliation: Department of Developmental Sciences, Marquette University School of Dentistry , Milwaukee, Wisconsin 53201, United States.
authors.forename: Erfan
authors.initials: E
authors.lastname: Dashtimoghadam
authors.affiliation: Department of Biomedical Engineering, Amirkabir University of Technology , Tehran, Iran.
authors.forename: Akbar
authors.initials: A
authors.lastname: Karkhaneh
authors.affiliation: Department of Biomedical Engineering, Amirkabir University of Technology , Tehran, Iran.
authors.forename: Mohammad Mahdi
authors.initials: MM
authors.lastname: Hasani-Sadrabadi
authors.forename: Karl I
authors.initials: KI
authors.lastname: Jacob
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D060326:Chemistry Techniques, Synthetic / Q000295:instrumentation*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry*; D065546:Drug Liberation; D005782:Gels; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D057446:Hydrodynamics; D006863:Hydrogen-Ion Concentration; D056656:Lab-On-A-Chip Devices; D008970:Molecular Weight; D049329:Nanostructures / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry*
chemical_list: D000464:Alginates; D004337:Drug Carriers; D005782:Gels; D006603:Hexuronic Acids; D012710:Serum Albumin, Bovine; D020723:Glucuronic Acid; D011094:Polyethyleneimine