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Pharmaceutics
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Smart Polymeric Nanocarriers for Drug and Gene Delivery
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Smart Polymeric Nanocarriers for Drug and Gene Delivery

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (20 November 2021) | Viewed by 28421

Special Issue Editor

Prof. Dr. Kostas Karatasos

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Guest Editor
Physical Chemistry Laboratory, Chemical Engineering Department, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: physicochemical properties of soft matter systems; structure/property relation; drug and gene delivery; composite materials and biopolymers; biomedical applications of polymers; molecular simulations
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recently, the development of smart polymer-based nanosized carriers has been among the most active areas of pharmaceutical and biomedical research. Numerous efforts have been focused on the improvement of synthetic protocols for the production of multifunctional and responsive polymeric nanocarriers, their physicochemical characterization, and the optimization of their properties towards the efficient delivery of their cargo. The aim of this Special Issue is to highlight recent advances in all aspects relevant to the use of polymeric nanosystems in drug and gene delivery technology. Strategies related to their cost-effective fabrication, problems and challenges associated with controlled and targeted delivery, their potential for multifaceted action in theranostics and nanomedicine, and prospects related to the molecular-level engineering of their properties are among the topics that will be of particular interest for this Special Issue.

Prof. Kostas Karatasos
Guest Editor

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Keywords

  • nanomedicine
  • theranostics
  • targeted delivery
  • polymer-based multifunctional nanocarriers
  • gene therapy
  • drug and gene complexation
  • controlled release
  • responsive polymeric hosts
  • molecular-level engineering

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Published Papers (7 papers)

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Research

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28 pages, 4190 KiB  
Article
Multi-Walled Carbon Nanotubes Decorated with Guanidinylated Dendritic Molecular Transporters: An Efficient Platform for the Selective Anticancer Activity of Doxorubicin
by Kyriaki-Marina Lyra, Archontia Kaminari, Katerina N. Panagiotaki, Konstantinos Spyrou, Sergios Papageorgiou, Elias Sakellis, Fotios K. Katsaros and Zili Sideratou
Pharmaceutics 2021, 13(6), 858; https://doi.org/10.3390/pharmaceutics13060858 - 9 Jun 2021
Cited by 14 | Viewed by 3074
Abstract
An efficient doxorubicin (DOX) drug delivery system with specificity against tumor cells was developed, based on multi-walled carbon nanotubes (MWCNTs) functionalized with guanidinylated dendritic molecular transporters. Acid-treated MWCNTs (oxCNTs) interacted both electrostatically and through hydrogen bonding and van der Waals attraction forces with [...] Read more.
An efficient doxorubicin (DOX) drug delivery system with specificity against tumor cells was developed, based on multi-walled carbon nanotubes (MWCNTs) functionalized with guanidinylated dendritic molecular transporters. Acid-treated MWCNTs (oxCNTs) interacted both electrostatically and through hydrogen bonding and van der Waals attraction forces with guanidinylated derivatives of 5000 and 25,000 Da molecular weight hyperbranched polyethyleneimine (GPEI5K and GPEI25K). Chemical characterization of these GPEI-functionalized oxCNTs revealed successful decoration with GPEIs all over the oxCNTs sidewalls, which, due to the presence of guanidinium groups, gave them aqueous compatibility and, thus, exceptional colloidal stability. These GPEI-functionalized CNTs were subsequently loaded with DOX for selective anticancer activity, yielding systems of high DOX loading, up to 99.5% encapsulation efficiency, while the DOX-loaded systems exhibited pH-triggered release and higher therapeutic efficacy compared to that of free DOX. Most importantly, the oxCNTs@GPEI5K-DOX system caused high and selective toxicity against cancer cells in a non-apoptotic, fast and catastrophic manner that cancer cells cannot recover from. Therefore, the oxCNTs@GPEI5K nanocarrier was found to be a potent and efficient nanoscale DOX delivery system, exhibiting high selectivity against cancerous cells, thus constituting a promising candidate for cancer therapy. Full article
(This article belongs to the Special Issue Smart Polymeric Nanocarriers for Drug and Gene Delivery)
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17 pages, 2555 KiB  
Article
HPMA-Based Copolymers Carrying STAT3 Inhibitor Cucurbitacin-D as Stimulus-Sensitive Nanomedicines for Oncotherapy
by Marina R. Tavares, Klára Hrabánková, Rafał Konefał, Martin Kaňa, Blanka Říhová, Tomáš Etrych, Milada Šírová and Petr Chytil
Pharmaceutics 2021, 13(2), 179; https://doi.org/10.3390/pharmaceutics13020179 - 28 Jan 2021
Cited by 6 | Viewed by 2301
Abstract
The study describes the synthesis, physicochemical properties, and biological evaluation of polymer therapeutics based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers intended for a tumor-targeted immuno-oncotherapy. Water-soluble linear and cholesterol-containing HPMA precursors were synthesized using controlled reversible addition–fragmentation chain transfer polymerization to reach molecular weight [...] Read more.
The study describes the synthesis, physicochemical properties, and biological evaluation of polymer therapeutics based on N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers intended for a tumor-targeted immuno-oncotherapy. Water-soluble linear and cholesterol-containing HPMA precursors were synthesized using controlled reversible addition–fragmentation chain transfer polymerization to reach molecular weight Mn about 2 × 104 g·mol−1 and low dispersity. These linear or self-assembled micellar conjugates, containing immunomodulatory agent cucurbitacin-D (CuD) or the anticancer drug doxorubicin (Dox) covalently bound by the hydrolytically degradable hydrazone bond, showed a hydrodynamic size of 10–30 nm in aqueous solutions. The CuD-containing conjugates were stable in conditions mimicking blood. Importantly, a massive release of active CuD in buffer mimicking the acidic tumor environment was observed. In vitro, both the linear (LP-CuD) and the micellar (MP-CuD) conjugates carrying CuD showed cytostatic/cytotoxic activity against several cancer cell lines. In a murine metastatic and difficult-to-treat 4T1 mammary carcinoma, only LP-CuD showed an anticancer effect. Indeed, the co-treatment with Dox-containing micellar polymer conjugate and LP-CuD showed potentiation of the anticancer effect. The results indicate that the binding of CuD, characterized by prominent hydrophobic nature and low bioavailability, to the polymer carrier allows a safe and effective delivery. Therefore, the conjugate could serve as a potential component of immuno-oncotherapy schemes within the next preclinical evaluation. Full article
(This article belongs to the Special Issue Smart Polymeric Nanocarriers for Drug and Gene Delivery)
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14 pages, 2196 KiB  
Article
Hyperthermia-Induced Controlled Local Anesthesia Administration Using Gelatin-Coated Iron–Gold Alloy Nanoparticles
by Chien-Kun Ting, Udesh Dhawan, Ching-Li Tseng, Cihun-Siyong Alex Gong, Wai-Ching Liu, Huai-De Tsai and Ren-Jei Chung
Pharmaceutics 2020, 12(11), 1097; https://doi.org/10.3390/pharmaceutics12111097 - 16 Nov 2020
Cited by 4 | Viewed by 2914
Abstract
The lack of optimal methods employing nanoparticles to administer local anesthesia often results in posing severe risks such as non-biocompatibility, in vivo cytotoxicity, and drug overdose to patients. Here, we employed magnetic field-induced hyperthermia to achieve localized anesthesia. We synthesized iron–gold alloy nanoparticles [...] Read more.
The lack of optimal methods employing nanoparticles to administer local anesthesia often results in posing severe risks such as non-biocompatibility, in vivo cytotoxicity, and drug overdose to patients. Here, we employed magnetic field-induced hyperthermia to achieve localized anesthesia. We synthesized iron–gold alloy nanoparticles (FeAu Nps), conjugated an anesthetic drug, Lidocaine, and coated the product with gelatin to increase the biocompatibility, resulting in a FeAu@Gelatin–Lidocaine nano-complex formation. The biocompatibility of this drug–nanoparticle conjugate was evaluated in vitro, and its ability to trigger local anesthesia was also evaluated in vivo. Upon exposure to high-frequency induction waves (HFIW), 7.2 ± 2.8 nm sized superparamagnetic nanoparticles generated heat, which dissociated the gelatin coating, thereby triggering Lidocaine release. MTT assay revealed that 82% of cells were viable at 5 mg/mL concentration of Lidocaine, indicating that no significant cytotoxicity was induced. In vivo experiments revealed that unless stimulated with HFIW, Lidocaine was not released from the FeAu@Gelatin–Lidocaine complex. In a proof-of-concept experiment, an intramuscular injection of FeAu@Gelatin–Lidocaine complex was administered to the rat posterior leg, which upon HFIW stimulation triggered an anesthetic effect to the injected muscle. Based on our findings, the FeAu@Gelatin–Lidocaine complex can deliver hyperthermia-induced controlled anesthetic drug release and serve as an ideal candidate for site-specific anesthesia administration. Full article
(This article belongs to the Special Issue Smart Polymeric Nanocarriers for Drug and Gene Delivery)
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29 pages, 4121 KiB  
Article
Chitosan Derivatives with Mucoadhesive and Antimicrobial Properties for Simultaneous Nanoencapsulation and Extended Ocular Release Formulations of Dexamethasone and Chloramphenicol Drugs
by Aikaterini Karava, Maria Lazaridou, Stavroula Nanaki, Georgia Michailidou, Evi Christodoulou, Margaritis Kostoglou, Hermis Iatrou and Dimitrios N. Bikiaris
Pharmaceutics 2020, 12(6), 594; https://doi.org/10.3390/pharmaceutics12060594 - 26 Jun 2020
Cited by 52 | Viewed by 4615
Abstract
The aim of this work was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with 2-acrylamido-2-methyl-1-propanesulfonic acid (AAMPS) and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSP) as appropriate nanocarriers for the simultaneous ocular administration of dexamethasone sodium phosphate (DxP) and chloramphenicol (CHL). The derivatives [...] Read more.
The aim of this work was to evaluate the effectiveness of neat chitosan (CS) and its derivatives with 2-acrylamido-2-methyl-1-propanesulfonic acid (AAMPS) and [2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (MEDSP) as appropriate nanocarriers for the simultaneous ocular administration of dexamethasone sodium phosphate (DxP) and chloramphenicol (CHL). The derivatives CS-AAMPS and CS-MEDSP have been synthesized by free-radical polymerization and their structure has been proved by Fourier-Transformed Infrared Spectroscopy (FT-IR) spectroscopy. Both derivatives exhibited low cytotoxicity, enhanced mucoadhesive properties and antimicrobial activity against Staphylococcus aureus (S.aureus) and Escherichia coli (E. coli). Encapsulation was performed via ionic crosslinking gelation using sodium tripolyphosphate (TPP) as the crosslinking agent. Dynamic light scattering measurements (DLS) showed that the prepared nanoparticles had bimodal distribution and sizes ranging from 50–200 nm and 300–800 nm. Drugs were encapsulated in their crystalline (CHL) or amorphous (DexSP) form inside nanoparticles and their release rate was dependent on the used polymer. The CHL dissolution rate was substantially enhanced compared to the neat drug and the release time was extended up to 7 days. The release rate of DexSP was much faster than that of CHL and was prolonged up to 3 days. Drug release modeling unveiled that diffusion is the main release mechanism for both drugs. Both prepared derivatives and their drug-loaded nanoparticles could be used for extended and simultaneous ocular release formulations of DexSP and CHL drugs. Full article
(This article belongs to the Special Issue Smart Polymeric Nanocarriers for Drug and Gene Delivery)
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17 pages, 3127 KiB  
Article
Formulation and In-Vitro Characterization of Chitosan-Nanoparticles Loaded with the Iron Chelator Deferoxamine Mesylate (DFO)
by Maria Lazaridou, Evi Christodoulou, Maria Nerantzaki, Margaritis Kostoglou, Dimitra A. Lambropoulou, Angeliki Katsarou, Kostas Pantopoulos and Dimitrios N. Bikiaris
Pharmaceutics 2020, 12(3), 238; https://doi.org/10.3390/pharmaceutics12030238 - 7 Mar 2020
Cited by 70 | Viewed by 5817
Abstract
The objective of this study was to develop chitosan (CS) nanoparticles (NPs) loaded with deferoxamine mesylate (DFO) for slow release of this iron-chelating drug. Drug nanoencapsulation was performed via ionic gelation of chitosan using sodium tripolyphosphate (TPP) as cross-linker. Nanoparticles with a size [...] Read more.
The objective of this study was to develop chitosan (CS) nanoparticles (NPs) loaded with deferoxamine mesylate (DFO) for slow release of this iron-chelating drug. Drug nanoencapsulation was performed via ionic gelation of chitosan using sodium tripolyphosphate (TPP) as cross-linker. Nanoparticles with a size ranging between 150 and 400 nm were prepared for neat CS/TPP with a 2/1 molar ratio while their yield was directly dependent on the applied stirring rate during the preparation process. DFO at different content (20, 45 and 75 wt %) was encapsulated into these nanoparticles. We found that drug loading correlates with increasing DFO content while the entrapment efficiency has an opposite behavior due to the high solubility of DFO. Hydrogen-bonding between amino and hydroxyl groups of DFO with reactive groups of CS were detected using FT-IR spectroscopy while X-ray diffraction revealed that DFO was entrapped in amorphous form in the CS nanoparticles. DFO release is directly dependent on the content of loaded drug, while model analysis revealed that the release mechanism of DFO for the CS/TPP nanoparticles is by diffusion. Treatment of murine RAW 264.7 macrophages with nanoencapsulated DFO promoted an increased expression of transferrin receptor 1 (TfR1) mRNA, a typical homeostatic response to iron deficiency. These data provide preliminary evidence for release of pharmacologically active DFO from the chitosan nanoparticles. Full article
(This article belongs to the Special Issue Smart Polymeric Nanocarriers for Drug and Gene Delivery)
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Review

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27 pages, 2166 KiB  
Review
An Overview of siRNA Delivery Strategies for Urological Cancers
by Nadia Halib, Nicola Pavan, Carlo Trombetta, Barbara Dapas, Rossella Farra, Bruna Scaggiante, Mario Grassi and Gabriele Grassi
Pharmaceutics 2022, 14(4), 718; https://doi.org/10.3390/pharmaceutics14040718 - 27 Mar 2022
Cited by 7 | Viewed by 3423
Abstract
The treatment of urological cancers has been significantly improved in recent years. However, for the advanced stages of these cancers and/or for those developing resistance, novel therapeutic options need to be developed. Among the innovative strategies, the use of small interfering RNA (siRNA) [...] Read more.
The treatment of urological cancers has been significantly improved in recent years. However, for the advanced stages of these cancers and/or for those developing resistance, novel therapeutic options need to be developed. Among the innovative strategies, the use of small interfering RNA (siRNA) seems to be of great therapeutic interest. siRNAs are double-stranded RNA molecules which can specifically target virtually any mRNA of pathological genes. For this reason, siRNAs have a great therapeutic potential for human diseases including urological cancers. However, the fragile nature of siRNAs in the biological environment imposes the development of appropriate delivery systems to protect them. Thus, ensuring siRNA reaches its deep tissue target while maintaining structural and functional integrity represents one of the major challenges. To reach this goal, siRNA-based therapies require the development of fine, tailor-made delivery systems. Polymeric nanoparticles, lipid nanoparticles, nanobubbles and magnetic nanoparticles are among nano-delivery systems studied recently to meet this demand. In this review, after an introduction about the main features of urological tumors, we describe siRNA characteristics together with representative delivery systems developed for urology applications; the examples reported are subdivided on the basis of the different delivery materials and on the different urological cancers. Full article
(This article belongs to the Special Issue Smart Polymeric Nanocarriers for Drug and Gene Delivery)
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37 pages, 5316 KiB  
Review
Miktoarm Star Polymers: Branched Architectures in Drug Delivery
by Victor Lotocki and Ashok Kakkar
Pharmaceutics 2020, 12(9), 827; https://doi.org/10.3390/pharmaceutics12090827 - 30 Aug 2020
Cited by 51 | Viewed by 5386
Abstract
Delivering active pharmaceutical agents to disease sites using soft polymeric nanoparticles continues to be a topical area of research. It is becoming increasingly evident that the composition of amphiphilic macromolecules plays a significant role in developing efficient nanoformulations. Branched architectures with asymmetric polymeric [...] Read more.
Delivering active pharmaceutical agents to disease sites using soft polymeric nanoparticles continues to be a topical area of research. It is becoming increasingly evident that the composition of amphiphilic macromolecules plays a significant role in developing efficient nanoformulations. Branched architectures with asymmetric polymeric arms emanating from a central core junction have provided a pivotal venue to tailor their key parameters. The build-up of miktoarm stars offers vast polymer arm tunability, aiding in the development of macromolecules with adjustable properties, and allows facile inclusion of endogenous stimulus-responsive entities. Miktoarm star-based micelles have been demonstrated to exhibit denser coronae, very low critical micelle concentrations, high drug loading contents, and sustained drug release profiles. With significant advances in chemical methodologies, synthetic articulation of miktoarm polymer architecture, and determination of their structure-property relationships, are now becoming streamlined. This is helping advance their implementation into formulating efficient therapeutic interventions. This review brings into focus the important discoveries in the syntheses of miktoarm stars of varied compositions, their aqueous self-assembly, and contributions their formulations are making in advancing the field of drug delivery. Full article
(This article belongs to the Special Issue Smart Polymeric Nanocarriers for Drug and Gene Delivery)
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