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Advances on Pharmaceutical Nanotechnology at the Interface with Biological Barriers
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Advances on Pharmaceutical Nanotechnology at the Interface with Biological Barriers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Nanochemistry".

Deadline for manuscript submissions: closed (15 May 2021) | Viewed by 19054

Special Issue Editors

Prof. Dr. Fabio Sonvico

E-Mail Website
Guest Editor
Interdept Ctr Biopharmanet TEC, Univ Parma, Parco Area delle Scienze 27-A, I-43124 Parma, Italy
Interests: pharmaceutical nanotechnology; nasal delivery; brain delivery; lung cancer; polysaccharides
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Sara Nicoli

E-Mail Website
Guest Editor
Department of Food and Drug, University of Parma, 43124 Parma, Italy
Interests: ocular drug delivery; dermal and transdermal drug delivery; innovative drug delivery systems for topical application; enhancement of drug absorption across biological tissues
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pharmaceutical nanotechnologies, over the past twenty years, have shown great potential for drug delivery due to their unique biopharmaceutical properties. The first breakthrough applications were related to the intravenous administration of anticancer drugs-loaded liposomes, opening the possibility to target tumor parenchyma via the enhanced-permeability and retention effect. However, more recently, the development of nanocarriers starting from biomimetic materials and with more or less complex surface modifications has widened the possibilities of drug-loaded nanoparticles, allowing for administration via different administration routes, stimuli or environment responsive drug delivery, active targeting of organs or specific cells and multiple actions, as in the case of theranostics. Still, the behavior of such complex delivery systems at the interface with biological barriers and their mechanism of action as delivery or carrier systems is often not completely elucidated.

The aim of this Special Issue is to go deep inside these challenges offered by pharmaceutical nanotechnologies, presenting recent innovations in nanomaterials for drug delivery, including biodegradable, surface-modified, stimuli-responsive or targeted nanoparticles, liposomes, and micelles designed to cross and investigated for their interactions with biological interfaces when administered via nonparenteral administration routes. As the Guest Editors, we cordially invite you to contribute a research paper or comprehensive review on any aspect related to this topic.

Prof. Fabio Sonvico
Prof. Sara Nicoli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Nanoparticles
  • Liposomes
  • Micelles
  • Biocompatible
  • Biodegradable
  • Stimuli-responsive
  • Targeting
  • Nonparenteral administration
  • Oral delivery
  • Nasal delivery
  • Pulmonary delivery
  • Topical delivery

Published Papers (6 papers)

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Research

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15 pages, 2979 KiB  
Article
Design and Characterization of Maltoheptaose-b-Polystyrene Nanoparticles, as a Potential New Nanocarrier for Oral Delivery of Tamoxifen
by Marcos Antonio Villetti, Adryana Rocha Clementino, Ilaria Dotti, Patricia Regina Ebani, Eride Quarta, Francesca Buttini, Fabio Sonvico, Annalisa Bianchera and Redouane Borsali
Molecules 2021, 26(21), 6507; https://doi.org/10.3390/molecules26216507 - 28 Oct 2021
Cited by 4 | Viewed by 1867
Abstract
Tamoxifen citrate (TMC), a non-steroidal antiestrogen drug used for the treatment of breast cancer, was loaded in a block copolymer of maltoheptaose-b-polystyrene (MH-b-PS) nanoparticles, a potential drug delivery system to optimize oral chemotherapy. The nanoparticles were obtained from self-assembly [...] Read more.
Tamoxifen citrate (TMC), a non-steroidal antiestrogen drug used for the treatment of breast cancer, was loaded in a block copolymer of maltoheptaose-b-polystyrene (MH-b-PS) nanoparticles, a potential drug delivery system to optimize oral chemotherapy. The nanoparticles were obtained from self-assembly of MH-b-PS using the standard and reverse nanoprecipitation methods. The MH-b-PS@TMC nanoparticles were characterized by their physicochemical properties, morphology, drug loading and encapsulation efficiency, and release kinetic profile in simulated intestinal fluid (pH 7.4). Finally, their cytotoxicity towards the human breast carcinoma MCF-7 cell line was assessed. The standard nanoprecipitation method proved to be more efficient than reverse nanoprecipitation to produce nanoparticles with small size and narrow particle size distribution. Moreover, tamoxifen-loaded nanoparticles displayed spherical morphology, a positive zeta potential and high drug content (238.6 ± 6.8 µg mL−1) and encapsulation efficiency (80.9 ± 0.4 %). In vitro drug release kinetics showed a burst release at early time points, followed by a sustained release profile controlled by diffusion. MH-b-PS@TMC nanoparticles showed higher cytotoxicity towards MCF-7 cells than free tamoxifen citrate, confirming their effectiveness as a delivery system for administration of lipophilic anticancer drugs. Full article
(This article belongs to the Special Issue Advances on Pharmaceutical Nanotechnology at the Interface with Biological Barriers)
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19 pages, 4850 KiB  
Article
Enhanced Oral Absorption of Icaritin by Using Mixed Polymeric Micelles Prepared with a Creative Acid-Base Shift Method
by Cheng Tang, Xiaoming Chen, Hua Yao, Haiyan Yin, Xiaoping Ma, Mingji Jin, Xin Lu, Quntao Wang, Kun Meng and Qipeng Yuan
Molecules 2021, 26(11), 3450; https://doi.org/10.3390/molecules26113450 - 06 Jun 2021
Cited by 14 | Viewed by 2578
Abstract
The purpose of this study was to develop mixed polymeric micelles with high drug loading capacity to improve the oral bioavailability of icaritin with Soluplus® and Poloxamer 407 using a creative acid-base shift (ABS) method, which exhibits the advantages of exclusion of [...] Read more.
The purpose of this study was to develop mixed polymeric micelles with high drug loading capacity to improve the oral bioavailability of icaritin with Soluplus® and Poloxamer 407 using a creative acid-base shift (ABS) method, which exhibits the advantages of exclusion of organic solvents, high drug loading and ease of scaling-up. The feasibility of the ABS method was successfully demonstrated by studies of icaritin-loaded polymeric micelles (IPMs). The prepared IPMs were characterized to have a spherical shape with a size of 72.74 ± 0.51 nm, and 13.18% drug loading content. In vitro release tests confirmed the faster release of icaritin from IPMs compared to an oil suspension. Furthermore, bioavailability of icaritin in IPMs in beagle dogs displayed a 14.9-fold increase when compared with the oil suspension. Transcellular transport studies of IPMs across Caco-2 cell monolayers confirmed that the IPMs were endocytosed in their intact forms through macropinocytosis, clathrin-, and caveolae-mediated pathways. In conclusion, the results suggested that the mixed micelles of Soluplus® and Poloxamer 407 could be a feasible drug delivery system to enhance oral bioavailability of icaritin, and the ABS method might be a promising technology for the preparation of polymeric micelles to encapsulate poorly water-soluble weakly acidic and alkaline drugs. Full article
(This article belongs to the Special Issue Advances on Pharmaceutical Nanotechnology at the Interface with Biological Barriers)
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10 pages, 8942 KiB  
Article
In-Vitro Cytotoxicity Study: Cell Viability and Cell Morphology of Carbon Nanofibrous Scaffold/Hydroxyapatite Nanocomposites
by Asmaa M. Abd El-Aziz, Azza El-Maghraby, Andrea Ewald and Sherif H. Kandil
Molecules 2021, 26(6), 1552; https://doi.org/10.3390/molecules26061552 - 11 Mar 2021
Cited by 8 | Viewed by 2546
Abstract
Electrospun carbon nanofibers (CNFs), which were modified with hydroxyapatite, were fabricated to be used as a substrate for bone cell proliferation. The CNFs were derived from electrospun polyacrylonitrile (PAN) nanofibers after two steps of heat treatment: stabilization and carbonization. Carbon nanofibrous (CNF)/hydroxyapatite (HA) [...] Read more.
Electrospun carbon nanofibers (CNFs), which were modified with hydroxyapatite, were fabricated to be used as a substrate for bone cell proliferation. The CNFs were derived from electrospun polyacrylonitrile (PAN) nanofibers after two steps of heat treatment: stabilization and carbonization. Carbon nanofibrous (CNF)/hydroxyapatite (HA) nanocomposites were prepared by two different methods; one of them being modification during electrospinning (CNF-8HA) and the second method being hydrothermal modification after carbonization (CNF-8HA; hydrothermally) to be used as a platform for bone tissue engineering. The biological investigations were performed using in-vitro cell counting, WST cell viability and cell morphology after three and seven days. L929 mouse fibroblasts were found to be more viable on the hydrothermally-modified CNF scaffolds than on the unmodified CNF scaffolds. The biological characterizations of the synthesized CNF/HA nanofibrous composites indicated higher capability of bone regeneration. Full article
(This article belongs to the Special Issue Advances on Pharmaceutical Nanotechnology at the Interface with Biological Barriers)
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23 pages, 7700 KiB  
Article
Nucleic Acid Delivery by Solid Lipid Nanoparticles Containing Switchable Lipids: Plasmid DNA vs. Messenger RNA
by Itziar Gómez-Aguado, Julen Rodríguez-Castejón, Mónica Vicente-Pascual, Alicia Rodríguez-Gascón, Ana del Pozo-Rodríguez and María Ángeles Solinís Aspiazu
Molecules 2020, 25(24), 5995; https://doi.org/10.3390/molecules25245995 - 18 Dec 2020
Cited by 28 | Viewed by 4557
Abstract
The development of safe and effective nucleic acid delivery systems remains a challenge, with solid lipid nanoparticle (SLN)-based vectors as one of the most studied systems. In this work, different SLNs were developed, by combination of cationic and ionizable lipids, for delivery of [...] Read more.
The development of safe and effective nucleic acid delivery systems remains a challenge, with solid lipid nanoparticle (SLN)-based vectors as one of the most studied systems. In this work, different SLNs were developed, by combination of cationic and ionizable lipids, for delivery of mRNA and pDNA. The influence of formulation factors on transfection efficacy, protein expression and intracellular disposition of the nucleic acid was evaluated in human retinal pigment epithelial cells (ARPE-19) and human embryonic kidney cells (HEK-293). A long-term stability study of the vectors was also performed. The mRNA formulations induced a higher percentage of transfected cells than those containing pDNA, mainly in ARPE-19 cells; however, the pDNA formulations induced a greater protein production per cell in this cell line. Protein production was conditioned by energy-dependent or independent entry mechanisms, depending on the cell line, SLN composition and kind of nucleic acid delivered. Vectors containing 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as unique cationic lipid showed better stability after seven months, which improved with the addition of a polysaccharide to the vectors. Transfection efficacy and long-term stability of mRNA vectors were more influenced by formulation-related factors than those containing pDNA; in particular, the SLNs containing only DOTAP were the most promising formulations for nucleic acid delivery. Full article
(This article belongs to the Special Issue Advances on Pharmaceutical Nanotechnology at the Interface with Biological Barriers)
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Review

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21 pages, 1703 KiB  
Review
Organic Nanocarriers for Bevacizumab Delivery: An Overview of Development, Characterization and Applications
by Aline de Cristo Soares Alves, Franciele Aline Bruinsmann, Silvia Stanisçuaski Guterres and Adriana Raffin Pohlmann
Molecules 2021, 26(14), 4127; https://doi.org/10.3390/molecules26144127 - 07 Jul 2021
Cited by 6 | Viewed by 3472
Abstract
Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In [...] Read more.
Bevacizumab (BCZ) is a recombinant humanized monoclonal antibody against the vascular endothelial growth factor, which is involved in the angiogenesis process. Pathologic angiogenesis is observed in several diseases including ophthalmic disorders and cancer. The multiple administrations of BCZ can cause adverse effects. In this way, the development of controlled release systems for BCZ delivery can promote the modification of drug pharmacokinetics and, consequently, decrease the dose, toxicity, and cost due to improved efficacy. This review highlights BCZ formulated in organic nanoparticles providing an overview of the physicochemical characterization and in vitro and in vivo biological evaluations. Moreover, the main advantages and limitations of the different approaches are discussed. Despite difficulties in working with antibodies, those nanocarriers provided advantages in BCZ protection against degradation guaranteeing bioactivity maintenance. Full article
(This article belongs to the Special Issue Advances on Pharmaceutical Nanotechnology at the Interface with Biological Barriers)
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16 pages, 541 KiB  
Review
Insights into Multifunctional Nanoparticle-Based Drug Delivery Systems for Glioblastoma Treatment
by Mohd Khan, Subuhi Sherwani, Saif Khan, Sultan Alouffi, Mohammad Alam, Khalid Al-Motair and Shahper Khan
Molecules 2021, 26(8), 2262; https://doi.org/10.3390/molecules26082262 - 14 Apr 2021
Cited by 10 | Viewed by 3286
Abstract
Glioblastoma (GB) is an aggressive cancer with high microvascular proliferation, resulting in accelerated invasion and diffused infiltration into the surrounding brain tissues with very low survival rates. Treatment options are often multimodal, such as surgical resection with concurrent radiotherapy and chemotherapy. The development [...] Read more.
Glioblastoma (GB) is an aggressive cancer with high microvascular proliferation, resulting in accelerated invasion and diffused infiltration into the surrounding brain tissues with very low survival rates. Treatment options are often multimodal, such as surgical resection with concurrent radiotherapy and chemotherapy. The development of resistance of tumor cells to radiation in the areas of hypoxia decreases the efficiency of such treatments. Additionally, the difficulty of ensuring drugs effectively cross the natural blood–brain barrier (BBB) substantially reduces treatment efficiency. These conditions concomitantly limit the efficacy of standard chemotherapeutic agents available for GB. Indeed, there is an urgent need of a multifunctional drug vehicle system that has potential to transport anticancer drugs efficiently to the target and can successfully cross the BBB. In this review, we summarize some nanoparticle (NP)-based therapeutics attached to GB cells with antigens and membrane receptors for site-directed drug targeting. Such multicore drug delivery systems are potentially biodegradable, site-directed, nontoxic to normal cells and offer long-lasting therapeutic effects against brain cancer. These models could have better therapeutic potential for GB as well as efficient drug delivery reaching the tumor milieu. The goal of this article is to provide key considerations and a better understanding of the development of nanotherapeutics with good targetability and better tolerability in the fight against GB. Full article
(This article belongs to the Special Issue Advances on Pharmaceutical Nanotechnology at the Interface with Biological Barriers)
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