PMID- 26938744 OWN - NLM STAT- MEDLINE DCOM- 20180529 LR - 20181202 IS - 1520-5827 (Electronic) IS - 0743-7463 (Linking) VI - 32 IP - 19 DP - 2016 May 17 TI - Microfluidic Directed Synthesis of Alginate Nanogels with Tunable Pore Size for Efficient Protein Delivery. PG - 4996-5003 LID - 10.1021/acs.langmuir.5b04645 [doi] AB - 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. FAU - Bazban-Shotorbani, Salime AU - Bazban-Shotorbani S AD - Department of Biomedical Engineering, Amirkabir University of Technology , Tehran, Iran. FAU - Dashtimoghadam, Erfan AU - Dashtimoghadam E AD - Department of Developmental Sciences, Marquette University School of Dentistry , Milwaukee, Wisconsin 53201, United States. FAU - Karkhaneh, Akbar AU - Karkhaneh A AD - Department of Biomedical Engineering, Amirkabir University of Technology , Tehran, Iran. FAU - Hasani-Sadrabadi, Mohammad Mahdi AU - Hasani-Sadrabadi MM AD - Department of Biomedical Engineering, Amirkabir University of Technology , Tehran, Iran. FAU - Jacob, Karl I AU - Jacob KI LA - eng PT - Journal Article DEP - 20160502 PL - United States TA - Langmuir JT - Langmuir : the ACS journal of surfaces and colloids JID - 9882736 RN - 0 (Alginates) RN - 0 (Drug Carriers) RN - 0 (Gels) RN - 0 (Hexuronic Acids) RN - 27432CM55Q (Serum Albumin, Bovine) RN - 8A5D83Q4RW (Glucuronic Acid) RN - 9002-98-6 (Polyethyleneimine) SB - IM MH - Alginates/*chemistry MH - Animals MH - Cattle MH - Chemistry Techniques, Synthetic/*instrumentation MH - Drug Carriers/*chemical synthesis/*chemistry MH - Drug Liberation MH - Gels MH - Glucuronic Acid/chemistry MH - Hexuronic Acids/chemistry MH - Hydrodynamics MH - Hydrogen-Ion Concentration MH - *Lab-On-A-Chip Devices MH - Molecular Weight MH - Nanostructures/*chemistry MH - Polyethyleneimine/chemistry MH - Serum Albumin, Bovine/*chemistry EDAT- 2016/03/05 06:00 MHDA- 2018/05/31 06:00 CRDT- 2016/03/04 06:00 PHST- 2016/03/04 06:00 [entrez] PHST- 2016/03/05 06:00 [pubmed] PHST- 2018/05/31 06:00 [medline] AID - 10.1021/acs.langmuir.5b04645 [doi] PST - ppublish SO - Langmuir. 2016 May 17;32(19):4996-5003. doi: 10.1021/acs.langmuir.5b04645. Epub 2016 May 2.