Biomaterials-Based Drug and Gene Delivery Systems

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

Deadline for manuscript submissions: closed (20 November 2020) | Viewed by 21067

Special Issue Editor


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Guest Editor
Department of Agriculture, Forestry and Bioresources, College of Agriculture and Life Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Republic of Korea
Interests: drug and gene delivery systems; biopolymers; nanomedicine

Special Issue Information

Dear Colleagues,

Over several decades, many drug and gene delivery systems based on diverse materials such as polymers, ceramics, and nanostructures have been developed for the improvement of bioavailability and pharmaceutical efficacy. Biomaterials (peptides, polysaccharides, nucleic acids, etc.) are usually biocompatible and possess their own inherent biological functionality (cell signal stimulation, targeting ability, anticancer activity, etc.), environmental (pH, temperature, salt, etc.) responsiveness, and chemical modifiability. Drugs and genes can be directly conjugated to the biomaterial-based delivery systems or loaded in biomaterial-based nanodelivery systems via hydrophobic or electrostatic interactions. Nowadays, novel biomaterials and their undiscovered properties are being continually discovered and, therefore, the application of biomaterials to drug and gene delivery systems would make breakthroughs in the development of efficient delivery systems by overcoming their current drawbacks.

Prof. Tae-il Kim
Guest Editor

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Keywords

  • biomaterials
  • drug and gene delivery systems
  • biocompatibility
  • biological functionality
  • environmental responsiveness
  • chemical modification
  • nanodelivery systems

Published Papers (7 papers)

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Research

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15 pages, 3965 KiB  
Article
Highly Osmotic Oxidized Sucrose-Crosslinked Polyethylenimine for Gene Delivery Systems
by Jaehong Park, Kyusik Kim, Sohee Jeong, Migyeom Lee and Tae-il Kim
Pharmaceutics 2021, 13(1), 87; https://doi.org/10.3390/pharmaceutics13010087 - 11 Jan 2021
Cited by 5 | Viewed by 2067
Abstract
In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by [...] Read more.
In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by 1H NMR and FTIR. The synthesized SP2K polymers could form positively charged (~40 mV zeta-potential) and nano-sized (150–200 nm) spherical polyplexes with plasmid DNA (pDNA). They showed lower cytotoxicity than PEI25K but concentration-dependent cytotoxicity. Among them, SP2K7 and SP2K10 showed higher transfection efficiency than PEI25K in both serum and serum-free conditions, revealing the good serum stability. It was found that SP2K polymers possessed high osmolality and endosome buffering capacity. The transfection experiments with cellular uptake inhibitors suggest that the transfection of SP2K polymers would progress by multiple pathways, including caveolae-mediated endocytosis. It was also thought that caveolae-mediated endocytosis of SP2K polyplexes would be facilitated through cyclooxygenase-2 (COX-2) expression induced by high osmotic pressure of SP2K polymers. Confocal microscopy results also supported that SP2K polyplexes would be internalized into cells via multiple pathways and escape endosomes efficiently via high osmolality and endosome buffering capacity. These results demonstrate the potential of SP2K polymers for gene delivery systems. Full article
(This article belongs to the Special Issue Biomaterials-Based Drug and Gene Delivery Systems)
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15 pages, 38611 KiB  
Article
Evaluation of Direct and Cell-Mediated Lactoferrin Gene Therapy for the Maxillofacial Area Abscesses in Rats
by Elima Agatieva, Said Ksembaev, Mikhail Sokolov, Vage Markosyan, Ilnaz Gazizov, Dmitry Tsyplakov, Maxim Shmarov, Irina Tutykhina, Boris Naroditsky, Denis Logunov, Oskar Pozdeev, Lidiya Morozova, Kamilya Yapparova and Rustem Islamov
Pharmaceutics 2021, 13(1), 58; https://doi.org/10.3390/pharmaceutics13010058 - 04 Jan 2021
Cited by 5 | Viewed by 2024
Abstract
Resistance to antibacterial therapy requires the discovery of new methods for the treatment of infectious diseases. Lactoferrin (LTF) is a well-known naïve first-line defense protein. In the present study, we suggested the use of an adenoviral vector (Ad5) carrying the human gene encoding [...] Read more.
Resistance to antibacterial therapy requires the discovery of new methods for the treatment of infectious diseases. Lactoferrin (LTF) is a well-known naïve first-line defense protein. In the present study, we suggested the use of an adenoviral vector (Ad5) carrying the human gene encoding LTF for direct and cell-mediated gene therapy of maxillofacial area phlegmon in rats. Abscesses were developed by injection of the purulent peritoneal exudate in the molar region of the medial surface of the mandible. At 3–4 days after phlegmon maturation, all rats received ceftriaxone and afterward were subcutaneously injected around the phlegmon with: (1) Ad5 carrying reporter gfp gene encoding green fluorescent protein (Ad5-GFP control group), (2) Ad5 carrying LTF gene (Ad5-LTF group), (3) human umbilical cord blood mononuclear cells (UCBC) transduced with Ad5-GFP (UCBC + Ad5-GFP group), and (4) UCBC transduced with Ad5-LTF (UCBC + Ad5-LTF group). Control rats developed symptoms considered to be related to systemic inflammation and were euthanized at 4–5 days from the beginning of the treatment. Rats from therapeutic groups demonstrated wound healing and recovery from the fifth to seventh day based on the type of therapy. Histological investigation of cervical lymph nodes revealed purulent lymphadenitis in control rats and activated lymphatic tissue in rats from the UCBC + Ad5-LTF group. Our results propose that both approaches of LTF gene delivery are efficient for maxillofacial area phlegmon recovery in rats. However, earlier wound healing and better outcomes in cervical lymph node remodeling in the UCBC + Ad5-LTF group, as well as the lack of direct exposure of the viral vector to the organism, which may cause toxic and immunogenic effects, suggest the benefit of cell-mediated gene therapy. Full article
(This article belongs to the Special Issue Biomaterials-Based Drug and Gene Delivery Systems)
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14 pages, 2333 KiB  
Article
Physicochemical Properties and Hematocompatibility of Layered Double Hydroxide-Based Anticancer Drug Methotrexate Delivery System
by Sang-Yong Jung, Hyoung-Mi Kim, Soonjae Hwang, Do-Gak Jeung, Ki-Jong Rhee and Jae-Min Oh
Pharmaceutics 2020, 12(12), 1210; https://doi.org/10.3390/pharmaceutics12121210 - 14 Dec 2020
Cited by 10 | Viewed by 2352
Abstract
A layered double hydroxide (LDH)-based anticancer delivery system was investigated in terms of crystalline phase, particle size, hydrodynamic radius, zeta potential, etc. through in vitro and in vivo study. Size controlled LDH with anticancer drug methotrexate (MTX) incorporation was successfully prepared through step-by-step [...] Read more.
A layered double hydroxide (LDH)-based anticancer delivery system was investigated in terms of crystalline phase, particle size, hydrodynamic radius, zeta potential, etc. through in vitro and in vivo study. Size controlled LDH with anticancer drug methotrexate (MTX) incorporation was successfully prepared through step-by-step hydrothermal reaction and ion-exchange reaction. The MTX-LDH was determined to have a neutral surface charge and strong agglomeration in the neutral aqueous condition due to the surface adsorbed MTX; however, the existence of proteins in the media dramatically reduced agglomeration, resulting in the hydrodynamic radius of MTX-LDH being similar to the primary particle size. The protein fluorescence quenching assay exhibited that MTX readily reduced the fluorescence of proteins, suggesting that the interaction between MTX and proteins was strong. On the other hand, MTX-LDH showed much less binding constant to proteins compared with MTX, implying that the protein interaction of MTX was effectively blocked by the LDH carrier. The in vivo hemolysis assay after intravenous injection of MTX-LDH showed neither significant reduction in red blood cell number nor membrane damage. Furthermore, the morphology of red blood cells in a mouse model did not change upon MTX-LDH injection. Scanning electron microscopy showed that the MTX-LDH particles were attached on the blood cells without serious denaturation of cellular morphology, taking advantage of the cell hitchhiking property. Full article
(This article belongs to the Special Issue Biomaterials-Based Drug and Gene Delivery Systems)
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12 pages, 4174 KiB  
Article
Cathepsin B-Responsive Liposomes for Controlled Anticancer Drug Delivery in Hep G2 Cells
by Seulgi Lee, Su Jeong Song, Jeil Lee, Tai Hwan Ha and Joon Sig Choi
Pharmaceutics 2020, 12(9), 876; https://doi.org/10.3390/pharmaceutics12090876 - 14 Sep 2020
Cited by 26 | Viewed by 3437
Abstract
In recent decades, several types of anticancer drugs that inhibit cancer cell growth and cause cell death have been developed for chemotherapeutic application. However, these agents are usually associated with side effects resulting from nonspecific delivery, which may induce cytotoxicity in healthy cells. [...] Read more.
In recent decades, several types of anticancer drugs that inhibit cancer cell growth and cause cell death have been developed for chemotherapeutic application. However, these agents are usually associated with side effects resulting from nonspecific delivery, which may induce cytotoxicity in healthy cells. To reduce the nonspecific delivery issue, nanoparticles have been successfully used for the delivery of anticancer drugs to specific target sites. In this study, a functional polymeric lipid, PEG-GLFG-K(C16)2 (PEG-GLFG, polyethylene glycol-Gly-Leu-Phe-Gly-Lys(C16)2), was synthesized to enable controlled anticancer drug delivery using cathepsin B enzyme-responsive liposomes. The liposomes composed of PEG-GLFG/DOTAP (1,2-dioleoyl-3-trimethylammonium-propane (chloride salt))/DPPC (dipalmitoylphosphatidylcholine)/cholesterol were prepared and characterized at various ratios. The GLFG liposomes formed were stable liposomes and were degraded when acted upon by cathepsin B enzyme. Doxorubicin (Dox) loaded GLFG liposomes (GLFG/Dox) were observed to exert an effective anticancer effect on Hep G2 cells in vitro and inhibit cancer cell proliferation in a zebrafish model. Full article
(This article belongs to the Special Issue Biomaterials-Based Drug and Gene Delivery Systems)
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18 pages, 4531 KiB  
Article
Effects of Decomplexation Rates on Ternary Gene Complex Transfection with α-Poly(l-Lysine) or ε-Poly(l-Lysine) as a Decomplexation Controller in An Easy-To-Transfect Cell or A Hard-To-Transfect Cell
by Kyoungnam Kim, Kitae Ryu, Hana Cho, Min Suk Shim, Yong-Yeon Cho, Joo Young Lee, Hye Suk Lee and Han Chang Kang
Pharmaceutics 2020, 12(6), 490; https://doi.org/10.3390/pharmaceutics12060490 - 28 May 2020
Cited by 2 | Viewed by 2013
Abstract
The tight binding of pDNA with a cationic polymer is the crucial requirement that prevents DNA degradation from undesired DNase attack to safely deliver the pDNA to its target site. However, cationic polymer-mediated strong gene holding limits pDNA dissociation from the gene complex, [...] Read more.
The tight binding of pDNA with a cationic polymer is the crucial requirement that prevents DNA degradation from undesired DNase attack to safely deliver the pDNA to its target site. However, cationic polymer-mediated strong gene holding limits pDNA dissociation from the gene complex, resulting in a reduction in transfection efficiency. In this study, to control the decomplexation rate of pDNA from the gene complex in a hard-to-transfect cell or an easy-to-transfect cell, either α-poly(l-lysine) (APL) or ε-poly(l-lysine) (EPL) was incorporated into branched polyethylenimine (bPEI)-based nanocomplexes (NCs). Compared to bPEI/pDNA NCs, the addition of APL or EPL formed smaller bPEI-APL/pDNA NCs with similar zeta potentials or larger bPEI-EPL/pDNA NCs with reduced zeta potentials, respectively, due to the different characteristics of the primary amines in the two poly(l-lysine)s (PLs). Interestingly, although both bPEI-APL/pDNA NCs and bPEI-EPL/pDNA NCs showed similar pDNA compactness to bPEI/pDNA NCs, the addition of APL or EPL resulted in slower or faster pDNA release, respectively, from the bPEI-PL/pDNA NCs than from the bPEI/pDNA NCs. bPEI-EPL/pDNA NCs with a decomplexation enhancer (i.e., EPL) improved the transfection efficiency (TE) in both a hard-to-transfect HepG2 cell and an easy-to-transfect HEK293 cell. However, although a decomplexation inhibitor (i.e., APL) reduced the TE of bPEI-APL/pDNA NCs in both cells, the degree of reduction in the TE could be compensated by PL-mediated enhanced nuclear delivery, particularly in HepG2 cells but not HEK293 cells, because both PLs facilitate nuclear localization of the gene complex per its cellular uptake. In conclusion, a decomplexation rate controller could be a potential factor to establish a high TE and design clinically available gene complex systems. Full article
(This article belongs to the Special Issue Biomaterials-Based Drug and Gene Delivery Systems)
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11 pages, 2373 KiB  
Article
Metal-Phenolic Network-Coated Hyaluronic Acid Nanoparticles for pH-Responsive Drug Delivery
by Jung Min Shin, Gwan Hyun Choi, Seok Ho Song, Hyewon Ko, Eun Sook Lee, Jae Ah Lee, Pil J. Yoo and Jae Hyung Park
Pharmaceutics 2019, 11(12), 636; https://doi.org/10.3390/pharmaceutics11120636 - 28 Nov 2019
Cited by 15 | Viewed by 4854
Abstract
Although self-assembled nanoparticles (SNPs) have been used extensively for targeted drug delivery, their clinical applications have been limited since most of the drugs are released into the blood before they reach their target site. In this study, metal-phenolic network (MPN)-coated SNPs (MPN-SNPs), which [...] Read more.
Although self-assembled nanoparticles (SNPs) have been used extensively for targeted drug delivery, their clinical applications have been limited since most of the drugs are released into the blood before they reach their target site. In this study, metal-phenolic network (MPN)-coated SNPs (MPN-SNPs), which consist of an amphiphilic hyaluronic acid derivative, were prepared to be a pH-responsive nanocarrier to facilitate drug release in tumor microenvironments (TME). Due to their amphiphilic nature, SNPs were capable of encapsulating doxorubicin (DOX), chosen as the model anticancer drug. Tannic acid and FeCl3 were added to the surface of the DOX-SNPs, which allowed them to be readily coated with MPNs as the diffusion barrier. The pH-sensitive MPN corona allowed for a rapid release of DOX and effective cellular SNP uptake in the mildly acidic condition (pH 6.5) mimicking TME, to which the hyaluronic acid was exposed to facilitate receptor-mediated endocytosis. The DOX-loaded MPN-SNPs exhibited a higher cytotoxicity for the cancer cells, suggesting their potential use as a drug carrier in targeted cancer therapy. Full article
(This article belongs to the Special Issue Biomaterials-Based Drug and Gene Delivery Systems)
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Review

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23 pages, 4909 KiB  
Review
Functional Nanofibrous Biomaterials of Tailored Structures for Drug Delivery—A Critical Review
by Zhen Li, Shunqi Mei, Yajie Dong, Fenghua She, Yongzhen Li, Puwang Li and Lingxue Kong
Pharmaceutics 2020, 12(6), 522; https://doi.org/10.3390/pharmaceutics12060522 - 08 Jun 2020
Cited by 28 | Viewed by 3525
Abstract
Nanofibrous biomaterials have huge potential for drug delivery, due to their structural features and functions that are similar to the native extracellular matrix (ECM). A wide range of natural and polymeric materials can be employed to produce nanofibrous biomaterials. This review introduces the [...] Read more.
Nanofibrous biomaterials have huge potential for drug delivery, due to their structural features and functions that are similar to the native extracellular matrix (ECM). A wide range of natural and polymeric materials can be employed to produce nanofibrous biomaterials. This review introduces the major natural and synthetic biomaterials for production of nanofibers that are biocompatible and biodegradable. Different technologies and their corresponding advantages and disadvantages for manufacturing nanofibrous biomaterials for drug delivery were also reported. The morphologies and structures of nanofibers can be tailor-designed and processed by carefully selecting suitable biomaterials and fabrication methods, while the functionality of nanofibrous biomaterials can be improved by modifying the surface. The loading and releasing of drug molecules, which play a significant role in the effectiveness of drug delivery, are also surveyed. This review provides insight into the fabrication of functional polymeric nanofibers for drug delivery. Full article
(This article belongs to the Special Issue Biomaterials-Based Drug and Gene Delivery Systems)
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