Browsing by Subject "Gene delivery"

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    The diffusion-driven microfluidic process to manufacture lipid-based nanotherapeutics with stealth properties for siRNA delivery
    (Elsevier, 2022-07) Eş, Ismail; Malfatti-Gasperini, A. A.; de la Torre, L. G.
    Our study investigated the manufacturing of lipid-based nanotherapeutics with stealth properties for siRNA delivery by employing a diffusion-driven microfluidic process in one or two-steps strategies to produce siRNA-loaded lipid nanocarriers and lipoplexes, respectively. In the one-step synthesis, siRNA in the aqueous phase is introduced from one inlet, while phospholipids dispersed in anhydrous ethanol are introduced from other inlets, generating the lipid nanocarriers. In the two-steps strategies, the pre-formed liposomes are complexed with siRNA. The process configuration with an aqueous diffusion barrier exerts a significant effect on the nanoaggregates synthesis. Dynamic light scattering data showed that lipid nanocarriers had a bigger particle diameter (298 ± 24 nm) and surface charge (43 ± 6 mV) compared to lipoplexes (194 ± 7 nm and 37.0 ± 0.4 mV). Moreover, DSPE-PEG(2000) was included in the formulation to synthesize lipid-based nanotherapeutics containing siRNA with stealth characteristics. The inclusion of PEG-lipid resulted in an increase in the surface charge of lipoplexes (from 33.7 ± 4.4–54.3 ± 1.6 mV), while a significant decrease was observed in the surface charge of lipid nanocarriers (30.3 ± 8.7 mV). The different structural assemblies were identified for lipoplex and lipid nanocarriers using Synchrotron SAXS. Lipid nanocarriers present a lower amount of multilayers than lipoplexes. Lipid-PEG insertion significantly influenced lipid nanocarriers’ characteristics, drastically decreasing the number of multilayers. This effect was not observed in lipoplexes. The association between process configuration, lipid composition, and its effect on the characteristics of lipid-based vector systems can generate fundamental insights, contributing to gene-based nanotherapeutics development.
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    Nanosized delivery systems for tissue regeneration
    (John Wiley & Sons, 2016-03-11) Çınar, Göksu; Mumcuoğlu, Didem; Tekinay, Ayşe B.; Güler, Mustafa O.; Güler, Mustafa O.; Tekinay, Ayşe B.
    This chapter focuses on advanced delivery of biologics including growth factors (GFs), cytokines, genes, or siRNAs using a variety of nanosized systems for different regeneration applications focusing on bone, cartilage, nervous system, and muscle regeneration strategies. Gene therapy provides permanent genetic alteration, but only transient actions of protein therapeutics can be needed for tissue regeneration applications. The limitations of biologics delivery and alternative strategies for overcoming recent problems are underlined presenting recent examples from the literature. In addition, specific targeting and cellular internalization strategies of biologies delivery for tissue regeneration are discussed for providing future perspectives to the readers in this field. Overall, it is believed that advanced nanosized delivery systems integrated with multicomponent designs will open new opportunities in delivery technologies and strategies for tissue regeneration.
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    Smart co-delivery of plasmid DNA and doxorubicin using MCM-chitosan-PEG polymerization functionalized with MUC-1 aptamer against breast cancer
    (Elsevier, 2024-03-19) Esmaeili, Yasaman; Dabiri, Arezou; Mashayekhi, Fariba; Rahimmanesh, Ilnaz; Bidram, Elham; Karbasi, Saeed; Rafienia, Mohammad; Javanmard, Shaghayegh Haghjooy; Ertaş, Yavuz Nuri; Zarrabi, Ali; Shariati, Laleh
    This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the copolymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies.