Journal of the American Chemical Society (JACS)2021ResearchNon-viral Gene Delivery
Dapeng Zhang, Elena N. Atochina-Vasserman, Devendra S. Maurya, Ning Huang, Qi Xiao, Nathan Ona, Matthew Liu, Hamna Shahnawaz, Houping Ni, Kyunghee Kim, Margaret M. Billingsley, Darrin J. Pochan, Michael J. Mitchell, Drew Weissman, Virgil Percec
Four-component lipid nanoparticles (LNPs) represent the leading non-viral vectors for mRNA delivery, but they have limitations including: (1) segregation of the neutral ionizable lipid as droplets in the LNP core, reducing transfection efficiency to ~1-2%; (2) the "PEG dilemma" where PEGylation increases circulation time but decreases cellular uptake and endosomal escape; and (3) instability at temperatures above -70°C. A one-component system. ### IAJD Libraries & DNP Formation | Parameter | Result | |---------------|------------| | Total IAJDs synthesized | 54 (6 libraries) | | In vitro active DNPs | 44/54 (81%) | | In vivo active DNPs | 31/54 (57%) | | DNPs.
Read the article →Nano Letters2021ResearchNon-viral Gene Delivery
Sarah J. Shepherd, Claude C. Warzecha, Sagar Yadavali, Rakan El-Mayta, Mohamad-Gabriel Alameh, Lili Wang, Drew Weissman, James M. Wilson, David Issadore, Michael J. Mitchell
Microfluidic mixing can produce precise LNPs but is limited in throughput, while bulk mixing is scalable but yields larger, heterogeneous particles with variable potency. A scalable microfluidic device is needed to produce potent RNA-LNPs across discovery and clinical scales. PMD achieved 18.4 L/h production, >100-fold higher throughput than a single microfluidic channel. - Mixing performance was uniform across 10× and 128× devices; 90% mixing channel length correlated linearly with ln(Pe).
Read the article →Nanomaterials2021ResearchNon-viral Gene Delivery
Tresa Lopez-Royo, Victor Sebastian, Laura Moreno-Martinez, Laura Uson, Cristina Yus, Teresa Alejo, Pilar Zaragoza, Rosario Osta, Manuel Arruebo, Raquel Manzano
CRISPR/Cas gene-editing components are often encoded on large plasmids (9–19 kb), which are difficult to encapsulate and transfect. Most PLGA nanoparticle (NP) gene-delivery studies use small nucleic acids (siRNA) or small plasmids (<6 kb), and the structural integrity and functional performance of large plasmids in PLGA NPs remain poorly characterized. There is a need to compare synthesis methods for encapsulating large plasmids without. pDNA stability: Batch ultrasound double emulsion completely degraded the 9.4 kb plasmid (standard) or left only 8.80% supercoiled (modified). Microfluidics-assisted double emulsion avoided degradation but produced only.
Read the article →Materials Science and Engineering: C2021ResearchDrug Delivery
Jiayu Zhou, Yishu Zhai, Jumei Xu, Tian Zhou, Lian Cen
PLGA microspheres are widely used for controlled drug release, but they often exhibit pronounced initial or mid-term burst release. A strategy is needed to finely tune drug release kinetics and suppress burst release, especially for water-soluble drugs. MSNs: Average size 119 nm; specific surface area 902.53 m²/g; pore volume 1.15 cm³/g; mean pore diameter 5.09 nm; maximum RB loading ~110 mg/g. - MSN-RB release: ~95% cumulative release within 56 h; Korsmeyer–Peppas n =.
Read the article →Biomaterials2021ReviewDrug Delivery
Shepherd Sj, Issadore D, Mitchell Mj.
Nanomedicine translation is limited by non-scalable, batch-variable bulk NP formulation methods that often produce large, polydisperse particles. Microfluidics offers precise control over microscale mixing and nanoprecipitation, enabling more reproducible NPs with controlled size, size distribution, and loading. This review summarizes microfluidic advances for lipid-, polymer-, and inorganic-based NPs. Representative quantitative findings from reviewed literature: - SHM-produced LNPs: 60–90 nm vs ~180 nm by pipette mixing; >90% hepatic gene silencing; up to 7-fold increased mRNA potency. - Parallelized SHM: 72 mL/min;.
Read the article →Biochemical Pharmacology*, Volume 173, 2020, Article 113648 DOI/2020ReviewDrug Delivery
Anne Vejux, Dehbia Abed-Vieillard, Khadija Hajji, Amira Zarrouk, John J. Mackrill, Shubhrima Ghosh, Thomas Nury, Aline Yamminse, Mohamed Zaibih, Wafa Mihoubi, Habiba Bouchabi, Boubker Nasser, Yael Grosjean, Gérard Lizard
7-Ketocholesterol (7KC) and 7β-hydroxycholesterol (7β-OHC) are major auto-oxidation products of cholesterol that accumulate in cardiovascular disease, age-related macular degeneration (ARMD), neurodegenerative disorders, and inflammatory bowel diseases. While their cytotoxicity (oxidative stress, organelle dysfunction, cell death, inflammation) is well documented in cell culture, the field lacks a consolidated understanding of how these oxysterols behave in vivo and which model systems (in vitro, animal, and emerging alternatives) are most appropriate for identifying pharmacological targets and protective molecules. This review addresses that gap by systematically surveying the models and mechanisms reported to date. --- 1. Oxiappotophagy is the dominant cell death mode: 7KC and 7β-OHC simultaneously induce oxidative stress (ROS overproduction: O₂⁻, H₂O₂), apoptosis (caspase activation, PARP cleavage, DNA fragmentation), and autophagy (
Read the article →Advanced Drug Delivery Reviews2020ReviewDrug Delivery
Nina Filipczak, Jiayi Pan, Satya Siva Kishan Yalamarty, Vladimir P. Torchilin
Liposomes remain an important nano-sized drug delivery system because of their biomimetic bilayer, ease of preparation, and biocompatibility, but clinical translation is still limited by reproducibility, scale-up, stability, and payload-specific barriers. The review updates recent advances in liposome preparation, excipients, administration routes, and novel modalities including nucleic acid therapies, CRISPR/Cas9, and immunotherapies. DOTAP-based liposome delivery of Cas9 and sgRNA plasmid achieved 39% gene-editing efficiency in knocking out a GFP reporter in HEK293 cells. - DOTAP/Chol/DOPE liposomes delivering miR-34b-5p to thyroid carcinoma reduced.
Read the article →RSC Advances2019ReviewDrug Delivery
Sima Rezvantalab And Mostafa Keshavarz Moraveji
PLGA is a biocompatible, biodegradable copolymer widely used in drug delivery systems (DDS), but conventional bulk synthesis methods suffer from poor control over particle size, broad size distribution, low drug loading/encapsulation efficiency, and burst release. Microfluidic systems offer a tightly controlled, reproducible alternative with low material consumption, but the field lacks a consolidated overview to guide researchers in selecting. ### 8.1 Microfluidic Type Determines Particle Size Scale - Droplet-based microfluidics → PLGA microparticles (typically 1–1000 μm) - Continuous microfluidics → PLGA nanoparticles (typically 10–1000 nm) - Exception: Lee.
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