Self-Organizing Nanovectors for Drug Delivery

A special issue of Pharmaceutics (ISSN 1999-4923).

Deadline for manuscript submissions: closed (30 April 2019) | Viewed by 45591

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Department of Pharmacy, Università degli Studi di Napoli Federico II, via Domenico Montesano 49, 80131 Naples, Italy
Interests: drug delivery; nanomedicine; drug targeting; liposomes; self-assembling nanoparticles; systemic delivery; brain delivery; wound healing
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Department of Drug Chemistry and Technologies, Faculty of Pharmacy and Medicine, "Sapienza" University of Rome, 000185 Rome, Italy
Interests: polysaccharide; hydrogels; nanohydrogels; drug delivery; tissue engineering
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Special Issue Information

Dear Colleagues,

Nanomedicines have been largely investigated as a useful tool for drug delivery and drug targeting. Despite the vast amount of literature on this subject and the growing number of formulations on the market or in clinical trials, the success rate of nanomedicines from bench to bed side is still low. Among the proposed approaches aiming to facilitate the technology transfer of nanomedicines, biomaterials and formulations able to spontaneously form nanoscale systems are very attractive. In this context, lipids and polymers have been largely proposed for the delivery of nucleic acids; polypeptides have been studied as building materials for drug delivery systems; inorganic or polymeric biomaterials have been combined to assemble in hybrid nanosystems, by mixing two or more components or by layer-by-layer strategy. Finally, formulations prepared by self-emulsifying have been proposed, especially for oral administration. All these approaches do not require high energy for the preparation and should be easy to transfer to large scale production with limited costs of production.

The aim of this Special Issue is to highlight the most recent innovations in the field of self-assembling and self-emulsifying delivery systems, thus providing an updated landscape of the state-of-art in the field, focusing both on the biomaterials and the applications.

Prof. Giuseppe De Rosa
Dr. Pietro Matricardi
Guest Editors

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Keywords

  • self-assembling
  • self-emulsifying
  • drug delivery systems
  • nanoparticles
  • lipoplexes
  • polyplexes
  • nanogels

Published Papers (11 papers)

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Research

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13 pages, 24605 KiB  
Article
Intracellular Delivery of Natural Antioxidants via Hyaluronan Nanohydrogels
by Elita Montanari, Chiara Di Meo, Tommasina Coviello, Virginie Gueguen, Graciela Pavon-Djavid and Pietro Matricardi
Pharmaceutics 2019, 11(10), 532; https://doi.org/10.3390/pharmaceutics11100532 - 14 Oct 2019
Cited by 18 | Viewed by 3209
Abstract
Natural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive molecules that show a number of therapeutic effects. However, their applications are remarkably limited by their poor water solubility, physico-chemical instability and low bioavailability. In the present work, it is [...] Read more.
Natural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive molecules that show a number of therapeutic effects. However, their applications are remarkably limited by their poor water solubility, physico-chemical instability and low bioavailability. In the present work, it is shown that self-assembled hyaluronan (HA)-based nanohydrogels (NHs) are taken up by endothelial cells (Human Umbilical Vein Endothelial Cells, HUVECs), preferentially accumulating in the perinuclear area of oxidatively stressed HUVECs, as evidenced by flow cytometry and confocal microscopy analyses. Furthermore, NHs are able to physically entrap and to significantly enhance the apparent water solubility of AX, RV and CU in aqueous media. AX/NHs, RV/NHs and CU/NHs systems showed good hydrodynamic diameters (287, 214 and 267 nm, respectively), suitable ζ-potential values (−45, −43 and −37 mV, respectively) and the capability to neutralise reactive oxygen species (ROS) in tube. AX/NHs system was also able to neutralise ROS in vitro and did not show any toxicity against HUVECs. This research suggests that HA-based NHs can represent a kind of nano-carrier suitable for the intracellular delivery of antioxidant agents, for the treatment of oxidative stress in endothelial cells. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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16 pages, 2537 KiB  
Article
Nanocarrier Lipid Composition Modulates the Impact of Pulmonary Surfactant Protein B (SP-B) on Cellular Delivery of siRNA
by Roberta Guagliardo, Pieterjan Merckx, Agata Zamborlin, Lynn De Backer, Mercedes Echaide, Jesus Pérez-Gil, Stefaan C. De Smedt and Koen Raemdonck
Pharmaceutics 2019, 11(9), 431; https://doi.org/10.3390/pharmaceutics11090431 - 23 Aug 2019
Cited by 13 | Viewed by 5006
Abstract
Two decades since the discovery of the RNA interference (RNAi) pathway, we are now witnessing the approval of the first RNAi-based treatments with small interfering RNA (siRNA) drugs. Nevertheless, the widespread use of siRNA is limited by various extra- and intracellular barriers, requiring [...] Read more.
Two decades since the discovery of the RNA interference (RNAi) pathway, we are now witnessing the approval of the first RNAi-based treatments with small interfering RNA (siRNA) drugs. Nevertheless, the widespread use of siRNA is limited by various extra- and intracellular barriers, requiring its encapsulation in a suitable (nanosized) delivery system. On the intracellular level, the endosomal membrane is a major barrier following endocytosis of siRNA-loaded nanoparticles in target cells and innovative materials to promote cytosolic siRNA delivery are highly sought after. We previously identified the endogenous lung surfactant protein B (SP-B) as siRNA delivery enhancer when reconstituted in (proteo) lipid-coated nanogels. It is known that the surface-active function of SP-B in the lung is influenced by the lipid composition of the lung surfactant. Here, we investigated the role of the lipid component on the siRNA delivery-promoting activity of SP-B proteolipid-coated nanogels in more detail. Our results clearly indicate that SP-B prefers fluid membranes with cholesterol not exceeding physiological levels. In addition, SP-B retains its activity in the presence of different classes of anionic lipids. In contrast, comparable fractions of SP-B did not promote the siRNA delivery potential of DOTAP:DOPE cationic liposomes. Finally, we demonstrate that the beneficial effect of lung surfactant on siRNA delivery is not limited to lung-related cell types, providing broader therapeutic opportunities in other tissues as well. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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17 pages, 5775 KiB  
Article
Nanolipid-Trehalose Conjugates and Nano-Assemblies as Putative Autophagy Inducers
by Eleonora Colombo, Michele Biocotino, Giulia Frapporti, Pietro Randazzo, Michael S. Christodoulou, Giovanni Piccoli, Laura Polito, Pierfausto Seneci and Daniele Passarella
Pharmaceutics 2019, 11(8), 422; https://doi.org/10.3390/pharmaceutics11080422 - 20 Aug 2019
Cited by 14 | Viewed by 4207
Abstract
The disaccharide trehalose is an autophagy inducer, but its pharmacological application is severely limited by its poor pharmacokinetics properties. Thus, trehalose was coupled via suitable spacers with squalene (in 1:2 and 1:1 stoichiometry) and with betulinic acid (1:2 stoichiometry), in order to yield [...] Read more.
The disaccharide trehalose is an autophagy inducer, but its pharmacological application is severely limited by its poor pharmacokinetics properties. Thus, trehalose was coupled via suitable spacers with squalene (in 1:2 and 1:1 stoichiometry) and with betulinic acid (1:2 stoichiometry), in order to yield the corresponding nanolipid-trehalose conjugates 1-Sq-mono, 2-Sq-bis and 3-Be-mono. The conjugates were assembled to produce the corresponding nano-assemblies (NAs) Sq-NA1, Sq-NA2 and Be-NA3. The synthetic and assembly protocols are described in detail. The resulting NAs were characterized in terms of loading and structure, and tested in vitro for their capability to induce autophagy. Our results are presented and thoroughly commented upon. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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16 pages, 4420 KiB  
Article
The Use of Artificial Gel Forming Bolalipids as Novel Formulations in Antimicrobial and Antifungal Therapy
by Nathalie Goergen, Matthias Wojcik, Simon Drescher, Shashank Reddy Pinnapireddy, Jana Brüßler, Udo Bakowsky and Jarmila Jedelská
Pharmaceutics 2019, 11(7), 307; https://doi.org/10.3390/pharmaceutics11070307 - 01 Jul 2019
Cited by 16 | Viewed by 3748
Abstract
The alarming growth of multi-drug resistant bacteria has led to a quest for alternative antibacterial therapeutics. One strategy to circumvent the already existing resistance is the use of photodynamic therapy. Antimicrobial photodynamic therapy (aPDT) involves the use of non-toxic photosensitizers in combination with [...] Read more.
The alarming growth of multi-drug resistant bacteria has led to a quest for alternative antibacterial therapeutics. One strategy to circumvent the already existing resistance is the use of photodynamic therapy. Antimicrobial photodynamic therapy (aPDT) involves the use of non-toxic photosensitizers in combination with light and in situ oxygen to generate toxic radical species within the microbial environment which circumvents the resistance building mechanism of the bacteria. Hydrogels are used ubiquitously in the biological and pharmaceutical fields, e.g., for wound dressing material or as drug delivery systems. Hydrogels formed by water-insoluble low-molecular weight gelators may potentially provide the much-needed benefits for these applications. Bolalipids are a superior example of such gelators. In the present work, two artificial bolalipids were used, namely PC-C32-PC and Me2PE-C32-Me2PE, which self-assemble in water into long and flexible nanofibers leading to a gelation of the surrounding solvent. The aim of the study was to create stable hydrogel formulations of both bolalipids and to investigate their applicability as a novel material for drug delivery systems. Furthermore, methylene blue—a well-known photosensitizer—was incorporated into the hydrogels in order to investigate the aPDT for the treatment of skin and mucosal infections using a custom designed LED device. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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19 pages, 1880 KiB  
Article
Antimicrobial Effect of Thymus capitatus and Citrus limon var. pompia as Raw Extracts and Nanovesicles
by Roberto Pinna, Enrica Filigheddu, Claudia Juliano, Alessandra Palmieri, Maria Manconi, Guy D’hallewin, Giacomo Petretto, Margherita Maioli, Carla Caddeo, Maria Letizia Manca, Giuliana Solinas, Antonella Bortone, Vincenzo Campanella and Egle Milia
Pharmaceutics 2019, 11(5), 234; https://doi.org/10.3390/pharmaceutics11050234 - 14 May 2019
Cited by 45 | Viewed by 4107
Abstract
In view of the increasing interest in natural antimicrobial molecules, this study screened the ability of Thymus capitatus (TC) essential oil and Citrus limon var. pompia (CLP) extract as raw extracts or incorporated in vesicular nanocarriers against Streptococcus mutans and Candida albicans. [...] Read more.
In view of the increasing interest in natural antimicrobial molecules, this study screened the ability of Thymus capitatus (TC) essential oil and Citrus limon var. pompia (CLP) extract as raw extracts or incorporated in vesicular nanocarriers against Streptococcus mutans and Candida albicans. After fingerprint, TC or CLP were mixed with lecithin and water to produce liposomes, or different ratios of water/glycerol or water/propylene glycol (PG) to produce glycerosomes and penetration enhancer vesicles (PEVs), respectively. Neither the raw extracts nor the nanovesicles showed cytotoxicity against human gingival fibroblasts at all the concentrations tested (1, 10, 100 μg/mL). The disc diffusion method, MIC-MBC/MFC, time-kill assay, and transmission electron microscopy (TEM) demonstrated the highest antimicrobial potential of TC against S. mutans and C. albicans. The very high presence of the phenol, carvacrol, in TC (90.1%) could explain the lethal effect against the yeast, killing up to 70% of Candida and not just arresting its growth. CLP, rich in polyphenols, acted in a similar way to TC in reducing S. mutans, while the data showed a fungistatic rather than a fungicidal activity. The phospholipid vesicles behaved similarly, suggesting that the transported extract was not the only factor to be considered in the outcomes, but also their components had an important role. Even if other investigations are necessary, TC and CLP incorporated in nanocarriers could be a promising and safe antimicrobial in caries prevention. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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15 pages, 1299 KiB  
Article
Exploring Light-Sensitive Nanocarriers for Simultaneous Triggered Antibiotic Release and Disruption of Biofilms Upon Generation of Laser-Induced Vapor Nanobubbles
by Eline Teirlinck, Alexandre Barras, Jing Liu, Juan C. Fraire, Tatu Lajunen, Ranhua Xiong, Katrien Forier, Chengnan Li, Arto Urtti, Rabah Boukherroub, Sabine Szunerits, Stefaan C. De Smedt, Tom Coenye and Kevin Braeckmans
Pharmaceutics 2019, 11(5), 201; https://doi.org/10.3390/pharmaceutics11050201 - 01 May 2019
Cited by 25 | Viewed by 4062
Abstract
Impaired penetration of antibiotics through bacterial biofilms is one of the reasons for failure of antimicrobial therapy. Hindered drug diffusion is caused on the one hand by interactions with the sticky biofilm matrix and on the other hand by the fact that bacterial [...] Read more.
Impaired penetration of antibiotics through bacterial biofilms is one of the reasons for failure of antimicrobial therapy. Hindered drug diffusion is caused on the one hand by interactions with the sticky biofilm matrix and on the other hand by the fact that bacterial cells are organized in densely packed clusters of cells. Binding interactions with the biofilm matrix can be avoided by encapsulating the antibiotics into nanocarriers, while interfering with the integrity of the dense cell clusters can enhance drug transport deep into the biofilm. Vapor nanobubbles (VNB), generated from laser irradiated nanoparticles, are a recently reported effective way to loosen up the biofilm structure in order to enhance drug transport and efficacy. In the present study, we explored if the disruptive force of VNB can be used simultaneously to interfere with the biofilm structure and trigger antibiotic release from light-responsive nanocarriers. The antibiotic tobramycin was incorporated in two types of light-responsive nanocarriers—liposomes functionalized with gold nanoparticles (Lip-AuNP) and graphene quantum dots (GQD)—and their efficacy was evaluated on Pseudomonas aeruginosa biofilms. Even though the anti-biofilm efficacy of tobramycin was improved by liposomal encapsulation, electrostatic functionalization with 70 nm AuNP unfortunately resulted in premature leakage of tobramycin in a matter of hours. Laser-irradiation consequently did not further improve P. aeruginosa biofilm eradication. Adsorption of tobramycin to GQD, on the other hand, did result in a stable formulation with high encapsulation efficiency, without burst release of tobramycin from the nanocarriers. However, even though laser-induced VNB formation from GQD resulted in biofilm disruption, an enhanced anti-biofilm effect was not achieved due to tobramycin not being efficiently released from GQD. Even though this study was unsuccessful in designing suitable nanocarriers for simultaneous biofilm disruption and light-triggered release of tobramycin, it provides insights into the difficulties and challenges that need to be considered for future developments in this regard. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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13 pages, 2218 KiB  
Article
Dual pH/Redox-Responsive Mixed Polymeric Micelles for Anticancer Drug Delivery and Controlled Release
by Yongle Luo, Xujun Yin, Xi Yin, Anqi Chen, Lili Zhao, Gang Zhang, Wenbo Liao, Xiangxuan Huang, Juan Li and Can Yang Zhang
Pharmaceutics 2019, 11(4), 176; https://doi.org/10.3390/pharmaceutics11040176 - 11 Apr 2019
Cited by 57 | Viewed by 5339
Abstract
Stimuli-responsive polymeric micelles (PMs) have shown great potential in drug delivery and controlled release in cancer chemotherapy. Herein, inspired by the features of the tumor microenvironment, we developed dual pH/redox-responsive mixed PMs which are self-assembled from two kinds of amphiphilic diblock copolymers (poly(ethylene [...] Read more.
Stimuli-responsive polymeric micelles (PMs) have shown great potential in drug delivery and controlled release in cancer chemotherapy. Herein, inspired by the features of the tumor microenvironment, we developed dual pH/redox-responsive mixed PMs which are self-assembled from two kinds of amphiphilic diblock copolymers (poly(ethylene glycol) methyl ether-b-poly(β-amino esters) (mPEG-b-PAE) and poly(ethylene glycol) methyl ether-grafted disulfide-poly(β-amino esters) (PAE-ss-mPEG)) for anticancer drug delivery and controlled release. The co-micellization of two copolymers is evaluated by measurement of critical micelle concentration (CMC) values at different ratios of the two copolymers. The pH/redox-responsiveness of PMs is thoroughly investigated by measurement of base dissociation constant (pKb) value, particle size, and zeta-potential in different conditions. The PMs can encapsulate doxorubicin (DOX) efficiently, with high drug-loading efficacy. The DOX was released due to the swelling and disassembly of nanoparticles triggered by low pH and high glutathione (GSH) concentrations in tumor cells. The in vitro results demonstrated that drug release rate and cumulative release are obviously dependent on pH values and reducing agents. Furthermore, the cytotoxicity test showed that the mixed PMs have negligible toxicity, whereas the DOX-loaded mixed PMs exhibit high cytotoxicity for HepG2 cells. Therefore, the results demonstrate that the dual pH/redox-responsive PMs self-assembled from PAE-based diblock copolymers could be potential anticancer drug delivery carriers with pH/redox-triggered drug release, and the fabrication of stimuli-responsive mixed PMs could be an efficient strategy for preparation of intelligent drug delivery platform for disease therapy. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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14 pages, 2136 KiB  
Article
Syringeable Self-Organizing Gels that Trigger Gold Nanoparticle Formation for Localized Thermal Ablation
by Sonia Cabana-Montenegro, Silvia Barbosa, Pablo Taboada, Angel Concheiro and Carmen Alvarez-Lorenzo
Pharmaceutics 2019, 11(2), 52; https://doi.org/10.3390/pharmaceutics11020052 - 26 Jan 2019
Cited by 5 | Viewed by 3018
Abstract
Block copolymer dispersions that form gels at body temperature and that additionally are able to reduce a gold salt to nanoparticles (AuNPs) directly in the final formulation under mild conditions were designed as hybrid depots for photothermal therapy. The in situ gelling systems [...] Read more.
Block copolymer dispersions that form gels at body temperature and that additionally are able to reduce a gold salt to nanoparticles (AuNPs) directly in the final formulation under mild conditions were designed as hybrid depots for photothermal therapy. The in situ gelling systems may retain AuNPs in the application zone for a long time so that localized elevations of temperature can be achieved each time the zone is irradiated. To carry out the work, dispersions were prepared covering a wide range of poloxamine Tetronic 1307:gold salt molar ratios in NaCl media (also varying from pure water to hypertonic solution). Even at copolymer concentrations well above the critical micelle concentration, the reducing power of the copolymer was maintained, and AuNPs were formed in few hours without extra additives. Varying the copolymer and NaCl concentrations allowed a fine tuning of nanoparticles’ shape from spherical to triangular nanoplates, which determined that the surface plasmon resonance showed a maximum intensity at 540 nm or at 1000 nm, respectively. The information gathered on the effects of (i) the poloxamine concentration on AuNPs’ size and shape under isotonic conditions, (ii) the AuNPs on the temperature-induced gelling transition, and (iii) the gel properties on the photothermal responsiveness of the AuNPs during successive irradiation cycles may help the rational design of one-pot gels with built-in temperature and light responsiveness. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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22 pages, 2895 KiB  
Article
Novel Formulations of C-Peptide with Long-Acting Therapeutic Potential for Treatment of Diabetic Complications
by Natalia Zashikhina, Vladimir Sharoyko, Mariia Antipchik, Irina Tarasenko, Yurii Anufrikov, Antonina Lavrentieva, Tatiana Tennikova and Evgenia Korzhikova-Vlakh
Pharmaceutics 2019, 11(1), 27; https://doi.org/10.3390/pharmaceutics11010027 - 11 Jan 2019
Cited by 26 | Viewed by 4216
Abstract
The development and application of novel nanospheres based on cationic and anionic random amphiphilic polypeptides with prolonged stability were proposed. The random copolymers, e.g., poly(l-lysine-co-d-phenylalanine) (P(Lys-co-dPhe)) and poly(l-glutamic acid-co- [...] Read more.
The development and application of novel nanospheres based on cationic and anionic random amphiphilic polypeptides with prolonged stability were proposed. The random copolymers, e.g., poly(l-lysine-co-d-phenylalanine) (P(Lys-co-dPhe)) and poly(l-glutamic acid-co-d-phenylalanine) (P(Glu-co-dPhe)), with different amount of hydrophilic and hydrophobic monomers were synthesized. The polypeptides obtained were able to self-assemble into nanospheres. Such characteristics as size, PDI and ζ-potential of the nanospheres were determined, as well as their dependence on pH was also studied. Additionally, the investigation of their biodegradability and cytotoxicity was performed. The prolonged stability of nanospheres was achieved via introduction of d-amino acids into the polypeptide structure. The cytotoxicity of nanospheres obtained was tested using HEK-293 cells. It was proved that no cytotoxicity up to the concentration of 500 µg/mL was observed. C-peptide delivery systems were realized in two ways: (1) peptide immobilization on the surface of P(Glu-co-dPhe) nanospheres; and (2) peptide encapsulation into P(Lys-co-dPhe) systems. The immobilization capacity and the dependence of C-peptide encapsulation efficiency, as well as maximal loading capacity, on initial drug concentration was studied. The kinetic of drug release was studied at model physiological conditions. Novel formulations of a long-acting C-peptide exhibited their effect ex vivo by increasing activity of erythrocyte Na+/K+-adenosine triphosphatase. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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12 pages, 1132 KiB  
Article
Chitosan-Based Polyelectrolyte Complexes for Doxorubicin and Zoledronic Acid Combined Therapy to Overcome Multidrug Resistance
by Simona Giarra, Silvia Zappavigna, Virginia Campani, Marianna Abate, Alessia Maria Cossu, Carlo Leonetti, Manuela Porru, Laura Mayol, Michele Caraglia and Giuseppe De Rosa
Pharmaceutics 2018, 10(4), 180; https://doi.org/10.3390/pharmaceutics10040180 - 09 Oct 2018
Cited by 9 | Viewed by 3031
Abstract
This study aimed to develop nanovectors co-encapsulating doxorubicin (Doxo) and zoledronic acid (Zol) for a combined therapy against Doxo-resistant tumors. Chitosan (CHI)-based polyelectrolyte complexes (PECs) prepared by ionotropic gelation technique were proposed. The influence of some experimental parameters was evaluated in order to [...] Read more.
This study aimed to develop nanovectors co-encapsulating doxorubicin (Doxo) and zoledronic acid (Zol) for a combined therapy against Doxo-resistant tumors. Chitosan (CHI)-based polyelectrolyte complexes (PECs) prepared by ionotropic gelation technique were proposed. The influence of some experimental parameters was evaluated in order to optimize the PECs in terms of size and polydispersity index (PI). PEC stability was studied by monitoring size and zeta potential over time. In vitro studies were carried out on wild-type and Doxo-resistant cell lines, to assess both the synergism between Doxo and Zol, as well as the restoring of Doxo sensitivity. Polymer concentration, incubation time, and use of a surfactant were found to be crucial to achieving small size and monodisperse PECs. Doxo and Zol, only when encapsulated in PECs, showed a synergistic antiproliferative effect in all the tested cell lines. Importantly, the incubation of Doxo-resistant cell lines with Doxo/Zol co-encapsulating PECs resulted in the restoration of Doxo sensitivity. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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Review

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16 pages, 2143 KiB  
Review
Latest Advances in the Development of Eukaryotic Vaults as Targeted Drug Delivery Systems
by Amanda Muñoz-Juan, Aida Carreño, Rosa Mendoza and José L. Corchero
Pharmaceutics 2019, 11(7), 300; https://doi.org/10.3390/pharmaceutics11070300 - 28 Jun 2019
Cited by 20 | Viewed by 4611
Abstract
The use of smart drug delivery systems (DDSs) is one of the most promising approaches to overcome some of the drawbacks of drug-based therapies, such as improper biodistribution and lack of specific targeting. Some of the most attractive candidates as DDSs are naturally [...] Read more.
The use of smart drug delivery systems (DDSs) is one of the most promising approaches to overcome some of the drawbacks of drug-based therapies, such as improper biodistribution and lack of specific targeting. Some of the most attractive candidates as DDSs are naturally occurring, self-assembling protein nanoparticles, such as viruses, virus-like particles, ferritin cages, bacterial microcompartments, or eukaryotic vaults. Vaults are large ribonucleoprotein nanoparticles present in almost all eukaryotic cells. Expression in different cell factories of recombinant versions of the “major vault protein” (MVP) results in the production of recombinant vaults indistinguishable from native counterparts. Such recombinant vaults can encapsulate virtually any cargo protein, and they can be specifically targeted by engineering the C-terminus of MVP monomer. These properties, together with nanometric size, a lumen large enough to accommodate cargo molecules, biodegradability, biocompatibility and no immunogenicity, has raised the interest in vaults as smart DDSs. In this work we provide an overview of eukaryotic vaults as a new, self-assembling protein-based DDS, focusing in the latest advances in the production and purification of this platform, its application in nanomedicine, and the current preclinical and clinical assays going on based on this nanovehicle. Full article
(This article belongs to the Special Issue Self-Organizing Nanovectors for Drug Delivery)
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