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Pharmaceutics
Special Issues
Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting
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Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (30 September 2022) | Viewed by 18057

Special Issue Editors

Dr. Angela Bonaccorso

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Guest Editor
Department of Drug and Health Sciences, University of Catania, V.le Andrea Doria, 6, 95125 Catania, Italy
Interests: drug delivery; nanocarriers; nanocrystals; nose-to-brain delivery; brain targeting; design of experiment; quality by design
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Rosario Pignatello

E-Mail Website
Guest Editor
Department of Drug and Health Sciences, University of Catania, V.le Andrea Doria, 6, 95125 Catania, Italy
Interests: drug delivery; nanomedicine; nanocarriers; biopolymers; pharmaceutical technology; ocular drug delivery; oral drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

Over the last fifty years, the development of biodegradable polymeric materials for pharmaceutical applications has advanced significantly. In the same way, the development of drug delivery systems based on natural and synthetic polymers exhibits exponential growth in pharmaceutical and biomedical fields.

Thanks to the tunable properties of polymeric biomaterials, carriers with different structure, size, shape, and surface charge can be obtained. Therefore, different kinds of micro- and nanosystems can be produced from polymeric materials using a wide variety of fabrication techniques. Micelles, dendrimers, micro- and nanoparticles, hydrogels, and nanogels are some of the most typical examples.  Polymers play a crucial role in modulating the delivery of active agents, providing a controlled release by means of different mechanisms. The pharmaceutical application of polymeric carriers is becoming increasingly crucial in diagnostics as well as in prophylaxis (vaccines) and therapy for various pathological conditions. Research efforts should progress and shed light on a robust understanding of polymer product interactions with biological systems. Based on the current and continuing relevance of this category of drug delivery systems, and looking ahead, this Special Issue will give readers a concise overview of the recent innovative design and application of controlled-release polymeric drug delivery systems. Topics including detailed physico-chemical and technological characterization of innovative polymeric systems and in vitro/in vivo correlations are warmly welcomed.                                                                         

Dr. Angela Bonaccorso
Prof. Dr. Rosario Pignatello
Guest Editors

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Keywords

  • cancer
  • biopolymers
  • gene complexation
  • ocular application
  • brain delivery
  • oral delivery
  • tissue regeneration
  • formulation
  • drug release
  • natural biomolecules
  • functional foods
  • targeted delivery
  • stimuli-responsive carriers
  • cellular interactions
  • antigens
  • nanovaccines

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Published Papers (6 papers)

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Research

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22 pages, 3071 KiB  
Article
Development of Lyophilised Eudragit® Retard Nanoparticles for the Sustained Release of Clozapine via Intranasal Administration
by Rosamaria Lombardo, Marika Ruponen, Jarkko Rautio, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Laura Calosi, Daniele Bani, Riikka Lampinen, Katja M. Kanninen, Anne M. Koivisto, Elina Penttilä, Heikki Löppönen and Rosario Pignatello
Pharmaceutics 2023, 15(5), 1554; https://doi.org/10.3390/pharmaceutics15051554 - 21 May 2023
Cited by 5 | Viewed by 2182
Abstract
Clozapine (CZP) is the only effective drug in schizophrenia resistant to typical antipsychotics. However, existing dosage forms (oral or orodispersible tablets, suspensions or intramuscular injection) show challenging limitations. After oral administration, CZP has low bioavailability due to a large first-pass effect, while the [...] Read more.
Clozapine (CZP) is the only effective drug in schizophrenia resistant to typical antipsychotics. However, existing dosage forms (oral or orodispersible tablets, suspensions or intramuscular injection) show challenging limitations. After oral administration, CZP has low bioavailability due to a large first-pass effect, while the i.m. route is often painful, with low patient compliance and requiring specialised personnel. Moreover, CZP has a very low aqueous solubility. This study proposes the intranasal route as an alternative route of administration for CZP, through its encapsulation in polymeric nanoparticles (NPs) based on Eudragit® RS100 and RL100 copolymers. Slow-release polymeric NPs with dimensions around 400–500 nm were formulated to reside and release CZP in the nasal cavity, where it can be absorbed through the nasal mucosa and reach the systemic circulation. CZP-EUD-NPs showed a controlled release of CZP for up to 8 h. Furthermore, to reduce mucociliary clearance and increase the residence time of NPs in the nasal cavity to improve drug bioavailability, mucoadhesive NPs were formulated. This study shows that the NPs already exhibited strong electrostatic interactions with mucin at time zero due to the presence of the positive charge of the used copolymers. Furthermore, to improve the solubility, diffusion and adsorption of CZPs and the storage stability of the formulation, it was lyophilised using 5% (w/v) HP-β-CD as a cryoprotectant. It ensured the preservation of the NPs’ size, PDI and charge upon reconstitution. Moreover, physicochemical characterisation studies of solid-state NPs were performed. Finally, toxicity studies were performed in vitro on MDCKII cells and primary human olfactory mucosa cells and in vivo on the nasal mucosa of CD-1 mice. The latter showed non-toxicity of B-EUD-NPs and mild CZP-EUD-NP-induced tissue abnormalities. Full article
(This article belongs to the Special Issue Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting)
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22 pages, 5045 KiB  
Article
Biotinylated Polymer-Ruthenium Conjugates: In Vitro and In Vivo Studies in a Triple-Negative Breast Cancer Model
by Leonor Côrte-Real, Ana Rita Brás, Adhan Pilon, Nuno Mendes, Ana Sofia Ribeiro, Tiago D. Martins, José Paulo S. Farinha, M. Conceição Oliveira, Fátima Gärtner, M. Helena Garcia, Ana Preto and Andreia Valente
Pharmaceutics 2022, 14(7), 1388; https://doi.org/10.3390/pharmaceutics14071388 - 30 Jun 2022
Cited by 13 | Viewed by 2688
Abstract
The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive [...] Read more.
The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(η5-CpR)(P)(2,2′-bipy-4,4′-PLA-biotin)][CF3SO3], where R is -H or -CH3 and P is P(C6H5)3, P(C6H4F)3 or P(C6H4OCH3)3, were tested against triple-negative breast cancer cells MDA-MB-231 showing IC50 values between 2.3–14.6 µM, much better than cisplatin, a classical chemotherapeutic drug, in the same experimental conditions. We selected compound 1 (where R is H and P is P(C6H5)3), for further studies as it was the one showing the best biological effect. In a competitive assay with biotin, we showed that cell uptake via SMVT receptors seems to be the main transport route into the cells for this compound, validating the strategy of including biotin in the design of the compound. The effects of the compound on the hallmarks of cancer show that the compound leads to apoptosis, interferes with proliferation by affecting the formation of cell colonies in a dose-dependent manner and disrupts the cell cytoskeleton. Preliminary in vivo assays in N: NIH(S)II-nu/nu mice show that the concentrations of compound 1 used in this experiment (maximum 4 mg/kg) are safe to use in vivo, although some signs of liver toxicity are already found. In addition, the new compound shows a tendency to control tumor growth, although not significantly. In sum, we showed that compound 1 shows promising anti-cancer effects, bringing a new avenue for triple-negative breast cancer therapy. Full article
(This article belongs to the Special Issue Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting)
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22 pages, 3126 KiB  
Article
Developing Novel Hydroxypropyl-β-Cyclodextrin-Based Nanosponges as Carriers for Anticancer Hydrophobic Agents: Overcoming Limitations of Host–Guest Complexes in a Comparative Evaluation
by Shohreh Peimanfard, Ali Zarrabi, Francesco Trotta, Adrián Matencio, Claudio Cecone and Fabrizio Caldera
Pharmaceutics 2022, 14(5), 1059; https://doi.org/10.3390/pharmaceutics14051059 - 15 May 2022
Cited by 11 | Viewed by 2779
Abstract
This study aimed to design and fabricate novel hydroxypropyl-β-cyclodextrin-based hypercrosslinked polymers, called nanosponges, as carriers for anticancer hydrophobic agents and compare them with host–guest complexes of hydroxypropyl-β-cyclodextrin, a remarkable solubilizer, to investigate their application in improving the pharmaceutical properties of the flavonoid naringenin, [...] Read more.
This study aimed to design and fabricate novel hydroxypropyl-β-cyclodextrin-based hypercrosslinked polymers, called nanosponges, as carriers for anticancer hydrophobic agents and compare them with host–guest complexes of hydroxypropyl-β-cyclodextrin, a remarkable solubilizer, to investigate their application in improving the pharmaceutical properties of the flavonoid naringenin, a model hydrophobic nutraceutical with versatile anticancer effects. For this purpose, three new nanosponges, crosslinked with pyromellitic dianhydride, citric acid, and carbonyldiimidazole, were fabricated. The carbonate nanosponge synthesized by carbonyldiimidazole presented the highest naringenin loading capacity (≈19.42%) and exerted significantly higher antiproliferative effects against MCF-7 cancer cells compared to free naringenin. Additionally, this carbonate nanosponge formed a stable nanosuspension, providing several advantages over the naringenin/hydroxypropyl-β-cyclodextrin host–guest complex, including an increase of about 3.62-fold in the loading capacity percentage, sustained released pattern (versus the burst pattern of host–guest complex), and up to an 8.3-fold increase in antiproliferative effects against MCF-7 cancer cells. Both naringenin-loaded carriers were less toxic to L929 murine fibroblast normal cells than MCF-7 cancer cells. These findings suggest that hydroxypropyl-β-cyclodextrin-based carbonate nanosponges could be a good candidate as a drug delivery system with potential applications in cancer treatment. Full article
(This article belongs to the Special Issue Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting)
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20 pages, 3153 KiB  
Article
Chitosan-Hyaluronan Nanoparticles for Vinblastine Sulfate Delivery: Characterization and Internalization Studies on K-562 Cells
by Carmela Cannavà, Federica De Gaetano, Rosanna Stancanelli, Valentina Venuti, Giuseppe Paladini, Francesco Caridi, Corneliu Ghica, Vincenza Crupi, Domenico Majolino, Guido Ferlazzo, Silvana Tommasini and Cinzia Anna Ventura
Pharmaceutics 2022, 14(5), 942; https://doi.org/10.3390/pharmaceutics14050942 - 26 Apr 2022
Cited by 18 | Viewed by 2815
Abstract
In the present study, we developed chitosan/hyaluronan nanoparticles (CS/HY NPs) for tumor targeting with vinblastine sulfate (VBL), that can be directed to the CD44 transmembrane receptor, over-expressed in cancer cells. NPs were prepared by coating with HY-preformed chitosan/tripolyphosphate (CS/TPP) NPs, or by polyelectrolyte [...] Read more.
In the present study, we developed chitosan/hyaluronan nanoparticles (CS/HY NPs) for tumor targeting with vinblastine sulfate (VBL), that can be directed to the CD44 transmembrane receptor, over-expressed in cancer cells. NPs were prepared by coating with HY-preformed chitosan/tripolyphosphate (CS/TPP) NPs, or by polyelectrolyte complexation of CS with HY. NPs with a mean hydrodynamic radius (RH) of 110 nm, 12% polydispersity index and negative zeta potential values were obtained by a direct complexation process. Transmission Electron Microscopy (TEM) images showed spherical NPs with a non-homogeneous matrix, probably due to a random localization of CS and HY interacting chains. The intermolecular interactions occurring between CS and HY upon NPs formation were experimentally evidenced by micro-Raman (µ-Raman) spectroscopy, through the analysis of the spectral changes of characteristic vibrational bands of HY during NP formation, in order to reveal the involvement of specific chemical groups in the process. Optimized NP formulation efficiently encapsulated VBL, producing a drug sustained release for 20 h. In vitro studies demonstrated a fast internalization of labeled CS/HY NPs (within 6 h) on K-562 human myeloid leukemia cells. Pre-saturation of CD44 by free HY produced a slowing-down of NP uptake over 24 h, demonstrating the need of CD44 for the internalization of HY-based NPs. Full article
(This article belongs to the Special Issue Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting)
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27 pages, 6160 KiB  
Article
Shell-Sheddable Micelles Based on Poly(ethylene glycol)-hydrazone-poly[R,S]-3-hydroxybutyrate Copolymer Loaded with 8-Hydroxyquinoline Glycoconjugates as a Dual Tumor-Targeting Drug Delivery System
by Adrian Domiński, Monika Domińska, Magdalena Skonieczna, Gabriela Pastuch-Gawołek and Piotr Kurcok
Pharmaceutics 2022, 14(2), 290; https://doi.org/10.3390/pharmaceutics14020290 - 26 Jan 2022
Cited by 14 | Viewed by 2802
Abstract
The development of selective delivery of anticancer drugs into tumor tissues to avoid systemic toxicity is a crucial challenge in cancer therapy. In this context, we evaluated the efficacy of a combination of nanocarrier pH-sensitivity and glycoconjugation of encapsulated drugs, since both vectors [...] Read more.
The development of selective delivery of anticancer drugs into tumor tissues to avoid systemic toxicity is a crucial challenge in cancer therapy. In this context, we evaluated the efficacy of a combination of nanocarrier pH-sensitivity and glycoconjugation of encapsulated drugs, since both vectors take advantage of the tumor-specific Warburg effect. Herein, we synthesized biodegradable diblock copolymer, a poly(ethylene glycol)-hydrazone linkage-poly[R,S]-3-hydroxybutyrate, which could further self-assemble into micelles with a diameter of ~55 nm. The hydrazone bond was incorporated between two copolymer blocks under an acidic pH, causing the shell-shedding of micelles which results in the drug’s release. The micelles were stable at pH 7.4, but decompose in acidic pH, as stated by DLS studies. The copolymer was used as a nanocarrier for 8-hydroxyquinoline glucose and galactose conjugates as well as doxorubicin, and exhibited pH-dependent drug release behavior. In vitro cytotoxicity, apoptosis, and life cycle assays studies of blank and drug-loaded micelles were performed on Normal Human Dermal Fibroblasts-Neonatal (NHDF-Neo), colon carcinoma (HCT-116), and breast cancer (MCF-7) for 24, 48, and 72 h. A lack of toxicity of blank micelles was demonstrated, whereas the glycoconjugates-loaded micelles revealed enhanced selectivity to inhibit the proliferation of cancer cells. The strategy of combining pH-responsive nanocarriers with glycoconjugation of the drug molecule provides an alternative to the modus operandi of designing multi-stimuli nanocarriers to increase the selectivity of anticancer therapy. Full article
(This article belongs to the Special Issue Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting)
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Review

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17 pages, 3273 KiB  
Review
PLGA-Gold Nanocomposite: Preparation and Biomedical Applications
by Alaaldin M. Alkilany, Ousama Rachid, Mahmoud Y. Alkawareek, Nashiru Billa, Anis Daou and Catherine J. Murphy
Pharmaceutics 2022, 14(3), 660; https://doi.org/10.3390/pharmaceutics14030660 - 17 Mar 2022
Cited by 14 | Viewed by 3707
Abstract
A composite system consisting of both organic and inorganic nanoparticles is an approach to prepare a new material exhibiting “the best of both worlds”. In this review, we highlight the recent advances in the preparation and applications of poly(lactic-co-glycolic acid)-gold nanoparticles (PLGA-GNP). With [...] Read more.
A composite system consisting of both organic and inorganic nanoparticles is an approach to prepare a new material exhibiting “the best of both worlds”. In this review, we highlight the recent advances in the preparation and applications of poly(lactic-co-glycolic acid)-gold nanoparticles (PLGA-GNP). With its current clinically use, PLGA-based nanocarriers have promising pharmaceutical applications and can “extract and utilize” the fascinating optical and photothermal properties of encapsulated GNP. The resulting “golden polymeric nanocarrier” can be tracked, analyzed, and visualized using the encapsulated gold nanoprobes which facilitate a better understanding of the hosting nanocarrier’s pharmacokinetics and biological fate. In addition, the “golden polymeric nanocarrier” can reveal superior nanotherapeutics that combine both the photothermal effect of the encapsulated gold nanoparticles and co-loaded chemotherapeutics. To help stimulate more research on the development of nanomaterials with hybrid and exceptional properties, functionalities, and applications, this review provides recent examples with a focus on the available chemistries and the rationale behind encapsulating GNP into PLGA nanocarriers that has the potential to be translated into innovative, clinically applicable nanomedicine. Full article
(This article belongs to the Special Issue Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting)
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