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Intelligent Polymeric Delivery System for Biomedical Applications

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A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Polymer Applications".

Deadline for manuscript submissions: closed (20 October 2022) | Viewed by 27384

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Special Issue Editors

Prof. Dr. San-Yuan Chen

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Guest Editor

Department of Material Science and Engineering, National Chiao Tung University, Hsinchu 30010, Taiwan
Interests: nanobiomaterials; drug delivery system; theranostics

Prof. Dr. Shwu-Jen Chang

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Guest Editor

Department of Biomedical Engineering, I-Shou University, Kaohsiung City 82445, Taiwan
Interests: biomaterials; tisuue engineering

Special Issue Information

Dear Colleagues,

Intelligent delivery systems have been proven to increase biomolecules’ targeting efficacy while reducing the side effects/toxicities of payloads, which are key factors for improving patient compliance. These smart stimuli-responsive intelligent delivery systems can be well designed in response to endogenous triggers such as pH variations, hormone level, enzyme concentration, or redox gradient, which are related to disease pathological characteristics. Furthermore, the exogenous stimulus, including temperature, magnetic field, light, and electric pulse/high energy radiation, can also be used to trigger or enhance the biomolecules’ release at diseased areas. So far, there has been a strong, growing interest in the development of polymeric-based carriers for application in various biomedical areas. In the academic field, stimuli-responsive polymeric delivery systems (PDS) including bioactive, natural or synthetic polymers have demonstrated several important contributions in several clinical uses. More importantly, these polymeric delivery platforms have the capability of simultaneously carrying different pharmaceutics, gene, and growth factors for various diseases and tissue regenerations. Therefore, the PDS will play significant roles in treating cancers, neurological disorders, infectious diseases, tissue engineering, regenerative medicine, cardiovascular diseases, or nutrient-encapsulated medical beauty in the near future.

This Special Issue, “Intelligent Polymeric Delivery System for Biomedical Applications”, will collect innovative, original research and review papers that focus on the scientific discussion and practical applications in the field of functional polymeric delivery systems for various biomedical applications. Topics include modern PDS formulation design, functionalized polymer-based carrier delivery ,and new therapies applied for (a) regenerative medicine, (b) infectious diseases, (c) neurological disorders, (d) tissue engineering, and (e) nutrient-encapsulated medical beauty. Topics of special interest include but are not limited to the preparation, chemical synthesis, structural design, material selection, characterization, morphology, and applications of advanced polymer nanocomposites. We hope that this Special Issue will promote academic research exchange, as well as introduce cutting-edge science and technology to this emerging medical field.

Prof. Dr. San-Yuan Chen
Prof. Dr. Shwu-Jen Chang
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. Polymers 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

Functionalized polymer-based composite materials
Responsive polymeric carriers
Intelligent delivery systems
Formulation design and synthesis for polymeric delivery
Tissue regeneration/repairs
Disease therapies

Published Papers (9 papers)

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Research

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16 pages, 4149 KiB

Open AccessArticle

The Treatment of Keloid Scars via Modulating Heterogeneous Gelatin-Structured Composite Microneedles to Control Transdermal Dual-Drug Release

by Yong-Ji Chen, Hung-Wei Cheng, Wan-Yu Yen, Jen-Hao Tsai, Chin-Yi Yeh, Ching-Jung Chen, Jen Tsai Liu, San-Yuan Chen and Shwu-Jen Chang

Polymers 2022, 14(20), 4436; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14204436 - 20 Oct 2022

Cited by 11 | Viewed by 2952

Abstract

Keloid scarring is an abnormal scar disease characterised by excessive proliferation of fibroblasts and over-deposition of collagen during wound healing. Although various treatments for keloid scars have been developed, preventive medicine is believed to be a promising strategy. The skin barrier limits the gentle topical administration of medicaments such as creams and hydrogel dressings, resulting in reduced therapeutic efficacy. In recent years, microneedles (MNs) have been regarded as an appreciable device for topical administration without inducing side effects, and they are painless and do not cause bleeding. In this study, an MN patch with controlled transdermal dual-drug release was developed to achieve combinatory treatment of keloid scars using a heterogeneous gelatin-structured composite MN. Gelatin hydrogel was used as a substrate to load gallic acid (GA) and quercetin-loaded amphiphilic gelatin nanoparticles to fabricate dual-drug heterogeneous composite MNs. The results of the insertion test and mechanical properties of the MNs showed that the heterogeneous composite MN patches could be self-pressed into the stratum corneum and control dual-drug release at different time periods. GA was released at an earlier stage to retard the proliferation of fibroblasts, and quercetin was released at a later stage as a strong antioxidant to erase the generation of reactive oxygen species. Furthermore, real-time quantitative polymerase chain reaction data indicated that the gene expression of fibroblasts (such as Col I and III) was downregulated in the dual-drug system. The above results demonstrate that using heterogeneous composite MNs with the combination of dual-drug pharmacology is beneficial for preventing keloid scar formation. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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21 pages, 3415 KiB

Open AccessArticle

Polymeric Microparticles: Synthesis, Characterization and In Vitro Evaluation for Pulmonary Delivery of Rifampicin

by Faiqa Falak Naz, Kifayat Ullah Shah, Zahid Rasul Niazi, Mansoor Zaman, Vuanghao Lim and Mulham Alfatama

Polymers 2022, 14(12), 2491; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14122491 - 19 Jun 2022

Cited by 5 | Viewed by 2546

Abstract

Rifampicin, a potent broad-spectrum antibiotic, remains the backbone of anti-tubercular therapy. However, it can cause severe hepatotoxicity when given orally. To overcome the limitations of the current oral therapy, this study designed inhalable spray-dried, rifampicin-loaded microparticles using aloe vera powder as an immune modulator, with varying concentrations of alginate and L-leucine. The microparticles were assessed for their physicochemical properties, in vitro drug release and aerodynamic behavior. The spray-dried powders were 2 to 4 µm in size with a percentage yield of 45 to 65%. The particles were nearly spherical with the tendency of agglomeration as depicted from Carr’s index (37 to 65) and Hausner’s ratios (>1.50). The drug content ranged from 0.24 to 0.39 mg/mg, with an association efficiency of 39.28 to 96.15%. The dissolution data depicts that the in vitro release of rifampicin from microparticles was significantly retarded with a higher L-leucine concentration in comparison to those formulations containing a higher sodium alginate concentration due to its hydrophobic nature. The aerodynamic data depicts that 60 to 70% of the aerosol mass was emitted from an inhaler with MMAD values of 1.44 to 1.60 µm and FPF of 43.22 to 55.70%. The higher FPF values with retarded in vitro release could allow sufficient time for the phagocytosis of synthesized microparticles by alveolar macrophages, thereby leading to the eradication of M. tuberculosis from these cells. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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17 pages, 3695 KiB

Open AccessArticle

High-Density Horizontal Stacking of Chondrocytes via the Synergy of Biocompatible Magnetic Gelatin Nanocarriers and Internal Magnetic Navigation for Enhancing Cartilage Repair

by Shan-Wei Yang, Yong-Ji Chen, Ching-Jung Chen, Jen-Tsai Liu, Chin-Yi Yang, Jen-Hao Tsai, Huai-En Lu, San-Yuan Chen and Shwu-Jen Chang

Polymers 2022, 14(4), 809; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14040809 - 19 Feb 2022

Cited by 5 | Viewed by 2100

Abstract

Osteoarthritis (OA) is a globally occurring articular cartilage degeneration disease that adversely affects both the physical and mental well-being of the patient, including limited mobility. One major pathological characteristic of OA is primarily related to articular cartilage defects resulting from abrasion and catabolic and proinflammatory mediators in OA joints. Although cell therapy has hitherto been regarded as a promising treatment for OA, the therapeutic effects did not meet expectations due to the outflow of implanted cells. Here, we aimed to explore the repair effect of magnetized chondrocytes using magnetic amphiphilic-gelatin nanocarrier (MAGNC) to enhance cellular anchored efficiency and cellular magnetic guidance (MG) toward the superficial zone of damaged cartilage. The results of in vitro experiments showed that magnetized chondrocytes could be rapidly guided along the magnetic force line to form cellular amassment. Furthermore, the Arg-Gly-Asp (RGD) motif of gelatin in MAGNC could integrate the interaction among cells to form cellular stacking. In addition, MAGNCs upregulated the gene expression of collagen II (Col II), aggrecan, and downregulated that of collagen I (Col I) to reduce cell dedifferentiation. In animal models, the magnetized chondrocytes can be guided into the superficial zone with the interaction between the internal magnetic field and MAGNC to form cellular stacking. In vivo results showed that the intensity of N-sulfated-glycosaminoglycans (sGAG) and Col II in the group of magnetized cells with magnetic guiding was higher than that in the other groups. Furthermore, smooth closure of OA cartilage defects was observed in the superficial zone after 8 weeks of implantation. The study revealed the significant potential of MAGNC in promoting the high-density stacking of chondrocytes into the cartilage surface and retaining the biological functions of implanted chondrocytes for OA cartilage repair. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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20 pages, 4568 KiB

Open AccessArticle

Pectin–Zeolite-Based Wound Dressings with Controlled Albumin Release

by Banu Kocaaga, Ozge Kurkcuoglu, Melkon Tatlier, Gizem Dinler-Doganay, Saime Batirel and Fatma Seniha Güner

Polymers 2022, 14(3), 460; https://0-doi-org.brum.beds.ac.uk/10.3390/polym14030460 - 24 Jan 2022

Cited by 10 | Viewed by 3210

Abstract

Hypoalbuminemia can lead to poor and delayed wound healing, while it is also associated with acute myocardial infarction, heart failure, malignancies, and COVID-19. In elective surgery, patients with low albumin have high risks of postoperative wound complications. Here, we propose a novel cost-effective wound dressing material based on low-methoxy pectin and NaA-zeolite particles with controlled albumin release properties. We focused on both albumin adsorption and release phenomena for wounds with excess exudate. Firstly, we investigated albumin dynamics and calculated electrostatic surfaces at experimental pH values in water by using molecular dynamics methods. Then, we studied in detail pectin–zeolite hydrogels with both adsorption and diffusion into membrane methods using different pH values and albumin concentrations. To understand if uploaded albumin molecules preserved their secondary conformation in different formulations, we monitored the effect of pH and albumin concentration on the conformational changes in albumin after it was released from the hydrogels by using CD-UV spectroscopy analyses. Our results indicate that at pH 6.4, BSA-containing films preserved the protein’s folded structure while the protein was being released to the external buffer solutions. In vitro wound healing assay indicated that albumin-loaded hydrogels showed no toxic effects on the fibroblast cells. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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15 pages, 3813 KiB

Open AccessArticle

Redox/pH-Responsive 2-in-1 Chimeric Nanoparticles for the Co-Delivery of Doxorubicin and siRNA

by Hsi-Chin Wu and Wei-Ting Kuo

Polymers 2021, 13(24), 4362; https://0-doi-org.brum.beds.ac.uk/10.3390/polym13244362 - 13 Dec 2021

Cited by 6 | Viewed by 2408

Abstract

The co-delivery of chemotherapy drugs and gene-suppressing small interfering RNA (siRNA) show promise for cancer therapy. The key to the clinical realization of this treatment model will be the development of a carrier system enabling the simultaneous delivery (“co-delivery” instead of combinatorial delivery) of chemotherapy and siRNA agents to cancer. In this study, a co-delivery system was developed from two individual components to form one integrated nanovehicle through a redox-sensitive thiol–disulfide bond for the synergistic delivery of chemotherapy and RNA silencing: doxorubicin (Dox)-loaded N,O-carboxymethyl chitosan (NOCC) complex with a thiolated hyaluronic acid (HA-SH) nanocarrier and dopamine (Dopa)-conjugated thiolated hyaluronic acid (SH-HA-Dopa)-coated calcium phosphate (CaP)-siRNA nanocarrier. The 2-in-1 chimeric nanoparticles (NPs) were structurally stable together in the storage environment and in the circulation. This smart system selectively releases Dox and siRNA into the cytosol. Furthermore, equipped with the tumor-targeting component HA, the co-delivery system shows specific targeting and high cellular uptake efficiency by receptor-mediated endocytosis. In summary, these dual-responsive (redox and pH), tumor-targeting smart 2-in-1 chimeric NPs show promise to be employed in functional co-delivery and tumor therapy. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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13 pages, 28157 KiB

Open AccessArticle

Development and Characterization of Eudragit-RL-100-Based Aceclofenac Sustained-Release Matrix Pellets Prepared via Extrusion/Spheronization

by Mohamed Abbas Ibrahim and Doaa Hasan Alshora

Polymers 2021, 13(22), 4034; https://0-doi-org.brum.beds.ac.uk/10.3390/polym13224034 - 21 Nov 2021

Cited by 3 | Viewed by 1937

Abstract

Aceclofenac (AC) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain in conditions such as rheumatoid arthritis, with frequent administration during the day. The formulation of sustained release matrix pellets can provide a promising alternative dosage form that controls the release of the drug, with less blood fluctuation and side effects—especially those related to the gastric system. The extrusion/spheronization technique was used to formulate AC matrix pellets. The response surface methodology (version 17.2.02.; Statgraphics Centurion) was used to study the impacts of Eudragit RL 100 and PVP K90 binder solution concentrations on the pellets’ wet mass peak torque, pellet size, and the release of the drug. Statistically, a significant synergistic effect of PVP K90 concentration on the peak torque and pellet size was observed (p = 0.0156 and 0.031, respectively), while Eudragit RL 100 showed significant antagonistic effects (p = 0.042 and 0.013, respectively). The peak torque decreased from 0.513 ± 0.022 to 0.41 ± 0.021 when increasing the Eudragit RL 100 from 0 to 20%, and the pellet size decreased from 0.914 ± 0.047 to 0.789 ± 0.074 nm. The tested independent factors did not significantly affect the drug release in the acidic medium within 2 h, but these pellet formulae maintained the drug release at less than 10% in the acidic medium (pH 1.2), which may decrease gastric irritation side effects. In contrast, a highly significant synergistic effect of Eudragit and highly antagonistic effect of the PVP solution on drug release in the alkaline-pH medium were observed (p = 0.002 and 0.007, respectively). The optimized pellet formula derived from the statistical program, composed of 3.21% Eudragit and 5% PVP solution, showed peak torque of 0.861 ± 0.056 Nm and pellet size of 1090 ± 85 µm, and resulted in a significant retardation effect on the release after 8 h compared to the untreated drug. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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16 pages, 5623 KiB

Open AccessArticle

A Four-Step Cascade Drug-Release Management Strategy for Transcatheter Arterial Chemoembolization (TACE) Therapeutic Applications

by Ying-Jiun Hsieh, Hung-Wei Cheng, Hung-Yu Chen and Ming-Wei Lee

Polymers 2021, 13(21), 3701; https://0-doi-org.brum.beds.ac.uk/10.3390/polym13213701 - 27 Oct 2021

Cited by 2 | Viewed by 1744

Abstract

The purpose of this study was to develop a four-step cascade drug-release system for transcatheter arterial chemoembolization (TACE) therapeutic applications according to disease-driven and patient-focused design theories. The four steps underlying these strategies involve the blockage of nutrient supply, nanoparticles, codelivery and the cell cytotoxic effect. Calibrated spherical gellan gum (GG) and nanoparticle-containing gellan gum microspheres were prepared using a water-in-oil emulsification method. Self-assembled nanoparticles featuring amine-functionalized graphene oxide (AFGO) as the doxorubicin (Dox) carrier were prepared. The results confirm that, as a drug carrier, AFGO–Dox nanoparticles can facilitate the transport of doxorubicin into HepG2 liver cancer cells. Subsequently, AFGO–Dox was introduced into gellan gum (GG) microspheres, thus forming GG/AFGO–Dox microspheres with a mean size of 200–700 μm. After a drug release experiment lasting 28 days, the amount of doxorubicin released from 674 and 226 μm GG/AFGO–Dox microspheres was 2.31 and 1.18 μg/mg, respectively. GG/AFGO–Dox microspheres were applied in a rabbit ear embolization model, where ischemic necrosis was visible on the ear after 12 days. Our aim for the future is to provide better embolization agents for transcatheter arterial chemoembolization (TACE) using this device. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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14 pages, 4841 KiB

Open AccessArticle

Ansamitocin P3-Loaded Gold-NanoCage Conjugated with Immune Checkpoint Inhibitor to Enhance Photo-Chemo-Thermal Maturation of Dendritic Cells for Hepatocellular Carcinoma

by Hung-Wei Cheng, Yu-Ling Ou, Chia-Chi Kuo, Hsin-Yi Tsao and Huai-En Lu

Polymers 2021, 13(16), 2726; https://0-doi-org.brum.beds.ac.uk/10.3390/polym13162726 - 15 Aug 2021

Cited by 6 | Viewed by 2146

Abstract

Immunotherapy is a newly developed method for cancer treatment, but still generates limited response in partial patients for hepatocellular carcinoma (HCC) because the immunity cycle is limited by the tumor microenvironment (TME). Herein, we introduce multifunctional gold nanocages (AuNCs)-based nanocarriers with Ansamitocin P3 (AP3) loaded and anti-PDL1 binding (AP3-AuNCs-anti-PDL1) which can combine photothermal therapy, chemotherapeutic agent-triggered DCs maturation, and checkpoint immunotherapy in one platform. The AP3-AuNCs-anti-PDL1 using Avidin-biotin to bind anti-PDL1 on the surface of AP3-AuNCs showed specifically cellular targeting compared to AuNCs, which can increase the immune responses. The AP3-AuNCs+NIR-10 min exhibited the highly activated DCs maturation with two-fold higher than control+NIR, which can be attributed to the significant release of AP3. The results illustrated the synergistic effect of tumor-associated antigens (TAAs) and controlled AP3 release under near infrared (NIR) in triggering effective DCs maturation. Among them, AP3 release played the more important role than the TAAs under PTT in promoting T-cell activation. These results illustrate the promising potential of AuNCs-based nanocarriers combined with AP3 and the checkpoint inhibitors to strengthen the positive loop of immunity cycle. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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Review

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23 pages, 4723 KiB

Open AccessEditor’s ChoiceReview

Advancements in the Blood–Brain Barrier Penetrating Nanoplatforms for Brain Related Disease Diagnostics and Therapeutic Applications

by Suresh Thangudu, Fong-Yu Cheng and Chia-Hao Su

Polymers 2020, 12(12), 3055; https://0-doi-org.brum.beds.ac.uk/10.3390/polym12123055 - 20 Dec 2020

Cited by 40 | Viewed by 7415

Abstract

Noninvasive treatments to treat the brain-related disorders have been paying more significant attention and it is an emerging topic. However, overcoming the blood brain barrier (BBB) is a key obstacle to most of the therapeutic drugs to enter into the brain tissue, which significantly results in lower accumulation of therapeutic drugs in the brain. Thus, administering the large quantity/doses of drugs raises more concerns of adverse side effects. Nanoparticle (NP)-mediated drug delivery systems are seen as potential means of enhancing drug transport across the BBB and to targeted brain tissue. These systems offer more accumulation of therapeutic drugs at the tumor site and prolong circulation time in the blood. In this review, we summarize the current knowledge and advancements on various nanoplatforms (NF) and discusses the use of nanoparticles for successful cross of BBB to treat the brain-related disorders such as brain tumors, Alzheimer’s disease, Parkinson’s disease, and stroke. Full article

(This article belongs to the Special Issue Intelligent Polymeric Delivery System for Biomedical Applications)

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