7 research outputs found
Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery
Instilling segregated cationic and lipophilic domains with an angular disposition in a trehalose-based trifaceted macrocyclic scaffold allows engineering patchy molecular nanoparticles leveraging directional interactions that emulate those controlling self-assembling processes in viral capsids. The resulting trilobular amphiphilic derivatives, featuring a Mickey Mouse architecture, can electrostatically interact with plasmid DNA (pDNA) and further engage in hydrophobic contacts to promote condensation into transfectious nanocomplexes. Notably, the topology and internal structure of the cyclooligosaccharide/pDNA co-assemblies can be molded by fine-tuning the valency and characteristics of the cationic and lipophilic patches, which strongly impacts the transfection efficacy in vitro and in vivo. Outstanding organ selectivities can then be programmed with no need of incorporating a biorecognizable motif in the formulation. The results provide a versatile strategy for the construction of fully synthetic and perfectly monodisperse nonviral gene delivery systems uniquely suited for optimization schemes by making cyclooligosaccharide patchiness the focus.Ministerio de Ciencia, Innovación y Universidades y Agencia Estatal de Investigación de España. RTI2018-097609-B-C21, RTI2018-097609-B-C22 y PID2019-105858RB-I00Universidad de Alcalá de Henares, Madrid. CCG19/CC-03
Trehalose-based Siamese twin amphiphiles with tunable self-assembling, DNA nanocomplexing and gene delivery properties
An original family of multivalent vectors encompassing gemini and facial amphiphilicity, namely cationic Siamese twin surfactants, has been prepared from the disaccharide trehalose; molecular engineering lets us modulate the self-assembling properties and the topology of the nanocomplexes with plasmid DNA for efficient gene delivery in vitro and in vivo.MINECO SAF2016-76083-R CTQ2015- 64425-C2-1-R CTQ2015-64425-C2-2-R RTI2018-097609-B-C21 RTI2018-097609-B-C22MCIU SAF2016-76083-R CTQ2015- 64425-C2-1-R CTQ2015-64425-C2-2-R RTI2018-097609-B-C21 RTI2018-097609-B-C22Junta de Andalucía FQM2012-1467FEDERFS
Trehalose-based siamese twin amphiphiles with tunable self-assembling, DNA nanocomplexing and gene delivery properties
An original family of multivalent vectors encompassing gemini and facial amphiphilicity, namely cationic Siamese twin surfactants, has been prepared fromthe disaccharide trehalose; molecular engineering lets us modulate the self-assembling properties and the topology of the nanocomplexes with plasmid DNA for efficient gene delivery in vitro and in vivo
Trifaceted Mickey Mouse Amphiphiles for Programmable Self-Assembly, DNA Complexation and Organ-Selective Gene Delivery
Instilling segregated cationic and lipophilic domains
with an angular disposition in a trehalose-based trifaceted
macrocyclic scaffold allows engineering patchy molecular
nanoparticles leveraging directional interactions that emulate
those controlling self-assembling processes in viral capsids.
The resulting trilobular amphiphilic derivatives, featuring a
Mickey Mouse architecture, can electrostatically interact with
plasmid DNA (pDNA) and further engage in hydrophobic
contacts to promote condensation into transfectious nanocomplexes.
Notably, the topology and internal structure of
the cyclooligosaccharide/pDNA co-assemblies can be molded
by fine-tuning the valency and characteristics of the cationic
and lipophilic patches, which strongly impacts the transfection
efficacy in vitro and in vivo. Outstanding organ
selectivities can then be programmed with no need of
incorporating a biorecognizable motif in the formulation. The
results provide a versatile strategy for the construction of fully
synthetic and perfectly monodisperse nonviral gene delivery
systems uniquely suited for optimization schemes by making
cyclooligosaccharide patchiness the focus.Peer reviewe
Biodegradable Guar-Gum-Based Super-Porous Matrices for Gastroretentive Controlled Drug Release in the Treatment of Helicobacter pylori: A Proof of Concept
An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices
Trehalose-based Siamese twin amphiphiles with tunable self-assembling, DNA nanocomplexing and gene delivery properties
An original family of multivalent vectors encompassing gemini and facial amphiphilicity, namely cationic Siamese twin surfactants, has been prepared fromthe disaccharide trehalose;molecular engineering lets us modulate the self-assembling properties and the topology of the nanocomplexes with plasmid DNA for efficient gene delivery in vitro and in vivo.The authors thank MINECO/MCIU (SAF2016-76083-R, CTQ2015-64425-C2-1-R, CTQ2015-64425-C2-2-R, RTI2018-097609-B-C21 and RTI2018-097609-B-C22), the Junta de Andalucía (FQM2012-1467) and the European Regional Development Funds (FEDER and FSE) for financial support. We acknowledge the CSIC (URICI) for supporting open access publication and the CITIUS (Univ. Seville) for technical support
Trifaceted Mickey Mouse Amphiphiles for Programmable Self‐Assembly, DNA Complexation and Organ‐Selective Gene Delivery
Instilling segregated cationic and lipophilic domains
with an angular disposition in a trehalose-based trifaceted
macrocyclic scaffold allows engineering patchy molecular
nanoparticles leveraging directional interactions that emulate
those controlling self-assembling processes in viral capsids.
The resulting trilobular amphiphilic derivatives, featuring a
Mickey Mouse architecture, can electrostatically interact with
plasmid DNA (pDNA) and further engage in hydrophobic
contacts to promote condensation into transfectious nanocomplexes.
Notably, the topology and internal structure of
the cyclooligosaccharide/pDNA co-assemblies can be molded
by fine-tuning the valency and characteristics of the cationic
and lipophilic patches, which strongly impacts the transfection
efficacy in vitro and in vivo. Outstanding organ
selectivities can then be programmed with no need of
incorporating a biorecognizable motif in the formulation. The
results provide a versatile strategy for the construction of fully
synthetic and perfectly monodisperse nonviral gene delivery
systems uniquely suited for optimization schemes by making
cyclooligosaccharide patchiness the focus.Peer reviewe