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Polymeric Colloidal Materials 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 (31 August 2019) | Viewed by 57038

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Special Issue Editors

Dr. Ming-Fa Hsieh

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1. Department of Biomedical Engineering, Chung Yuan Christian University, Taoyuan 32023, Taiwan
2. Center for Minimally-Invasive Medical Devices and Technologies, Chung Yuan Christian University, Taoyuan 32023, Taiwan
Interests: biomedical polymer; polymeric micelles; polymeric nanoparticles; cartilage regeneration; near infrared medical imagings; polyermic membranes for drug delivery
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Prof. Dr. Jiashing Yu

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Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan
Interests: costumed-design of Biomaterials; surface modification of biomaterials to enhance cell and extracellular matrix interaction; antibody and peptides conjugated nanoparticles as biosensors and drug delivery vehicles for cancer therapy; Stem Cell and Tissue engineering; cell encapsulation and 3D culture; biological microbubbles for cardiac and stem cells
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Prof. Dr. Chun-Jen Huang

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Department of Chemical and Materials Engineering, National Central University, Taoyuan, Taiwan
Interests: plasmonic biosensors; functional biointerfaces; antifouling materials; zwitterionic materials
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Special Issue Information

Dear Colleagues,

Colloids is generally known as the dispersion of microscopic particles in a liquid, gas, and condensed phase. Because of the tunable molecular structures, polymeric colloids can be tailor-made to show a superlattice architecture. In recent decades, emerging technologies have enabled the fabrication of polymeric colloids in a nanoscopic scale. Classically, polymeric colloids are produced via the self-assembly of polymer chains in solution. Scientists have gained experience in engineering the architectures of colloids from naturally-occurring polymers, e.g., biomimetic approaches. Alternatively, synthetic polymers are also employed for the self-assembly of colloids. With modern technologies, high-throughput synthesis of polymeric colloids is realized by microfluidics and photolithography.

In addition to the synthesis of polymeric colloids, the physicochemical properties and featured properties, such as biological or optoelectronic behaviors, are crucial for biomedical applications. These properties should be comprehensively characterized with advanced instrumentations.

Polymeric colloids are widely applied for therapy and diagnosis, as well. For example, the nanosized liposome of doxorubicine has been used clinically for cancer therapy. With regard to advanced functionality, nanodrugs combined with diagnostic agents have been discovered and termed as theranostics. It is expected that more and more biomedical applications of polymeric colloids will be introduced in the near future.

The aim of this Special Issue is to highlight the progress and fundamental aspects for the synthesis, characterization, properties, and biomedical application of colloids made of synthetic polymers and biologically-relevant macromolecules, as well as their copolymers and nanocomposites.

Dr. Ming-Fa Hsieh
Dr. Jiashing Yu
Dr. Chun-Jen Huang
Guest Editors

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Keywords

Polymeric colloids
biomedical
nanoparticles
polymeric micelles
liposomes
solid lipid nanoparticles
theranostics

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Published Papers (12 papers)

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15 pages, 4099 KiB

Open AccessArticle

CD133 Targeted PVP/PMMA Microparticle Incorporating Levamisole for the Treatment of Ovarian Cancer

by Yu-Chi Wang, Meng-Yi Bai, Ying-Ting Yeh, Sung-Ling Tang and Mu-Hsien Yu

Polymers 2020, 12(2), 479; https://doi.org/10.3390/polym12020479 - 20 Feb 2020

Cited by 4 | Viewed by 3163

Abstract

Levamisole (LEVA) is used to treat worm infections, but it can also inhibit cancer cell growth by inhibiting the aldehyde dehydrogenase pathway. Therefore, here, we developed a drug carrier targeting CD133, a biomarker overexpressed in ovarian cancer cells. The particle structure and cytotoxicity of the prepared LEVA-containing particles—called LEVA/PVP/PMMA microparticles (MPs) (because it used matrix material polyvinylpyrrolidone (PVP) and poly(methylmethacrylate) (PMMA))—were investigated in the ovarian cancer cell lines SKOV-3 and CP70. The particle size of the MPs was determined to be 1.0–1.5 µm and to be monodispersed. The hydrophilic property of PVP created a porous MP surface after the MPs were soaked in water for 20 min, which aided the leaching of the hydrophilic LEVA out of the MPs. The encapsulation efficiency of LEVA/PVP/PMMA MPs could reach up to 20%. Free-form LEVA released 50% of drugs in <1 h and 90% of drugs in 1 day, whereas the drug release rate of LEVA/PVP/PMMA MPs was much slower; 50% released in 4 h and only 70% of drugs released in 1 day. In the in vitro cell model test, 5 mM free-form LEVA and 0.1 g/mL CD133 targeted LEVA/PVP/PMMA MPs reduced SKOV-3 cell viability by 60%; 0.1 g/mL LEVA/PVP/PMMA MPs was equivalent to a similar dosage of the free drug. In addition, the cytotoxicity of CD133-conjugated LEVA/PVP/PMMA MPs shows a different cytotoxicity response toward cell lines. For SKOV-3 cells, treatment with free-form LEVA or CD133-conjugated LEVA/PVP/PMMA MPs exerted dose-dependent cytotoxic effects on SKOV-3 cell viability. However, CD133-conjugated LEVA/PVP/PMMA MPs demonstrated no significant dose-dependent cytotoxic efficacy toward CP70 cells. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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12 pages, 3425 KiB

Open AccessArticle

Amphiphilic Block Copolymers Bearing Hydrophobic γ-Tocopherol Groups with Labile Acetal Bond

by Shotaro Yukioka, Takuya Kitadume, Suchismita Chatterjee, Gan Ning, Tooru Ooya and Shin-ichi Yusa

Polymers 2020, 12(1), 36; https://doi.org/10.3390/polym12010036 - 25 Dec 2019

Viewed by 3453

Abstract

High concentrations of γ-tocopherol (γTCP) tend to show antioxidant, anti-inflammatory, and anticancer effects. In this study, we prepared polymer micelles under acidic conditions with a controlled release of γTCP due to the decomposition of pendant acetal bonds. First, a precursor diblock copolymer composed of poly(ethylene glycol) (PEG) and acrylic acid (AA) was prepared. This was followed by the synthesis of an amphiphilic diblock copolymer (PEG₅₄-P(AA/VE6/γTCP29)₁₄₀), incorporated into hydrophobic γTCP pendant groups attached to the main chain through an acetal bond. The prepared PEG₅₄-P(AA/VE6/γTCP29)₁₄₀ was further dispersed in water to form polymer micelles composed of hydrophobic cores that were generated from a hydrophobic block containing γTCPs and hydrophilic shells on the surface. Under acidic conditions, γTCP was then released from the core of the polymer micelles due to the decomposition of the pendant acetal bonds. In addition, polymer micelles swelled under acidic conditions due to hydration of the core. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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17 pages, 4398 KiB

Open AccessArticle

Effects of Bilayer Nanofibrous Scaffolds Containing Curcumin/Lithospermi Radix Extract on Wound Healing in Streptozotocin-Induced Diabetic Rats

by Bo-Yin Yang, Chung-Hsuan Hu, Wei-Chien Huang, Chien-Yi Ho, Chun-Hsu Yao and Chiung-Hua Huang

Polymers 2019, 11(11), 1745; https://doi.org/10.3390/polym11111745 - 24 Oct 2019

Cited by 45 | Viewed by 3720

Abstract

Impaired growth factor production, angiogenic response, macrophage function, and collagen accumulation have been shown to delay wound healing. Delayed wound healing is a debilitating complication of diabetes that leads to significant morbidity. In this study, curcumin and Lithospermi radix (LR) extract, which are used in traditional Chinese herbal medicine, were added within nanofibrous membranes to improve wound healing in a streptozotocin (STZ)-induced diabetic rat model. Gelatin-based nanofibers, which were constructed with curcumin and LR extract at a flow rate of 0.1 mL/hour and an applied voltage of 20 kV, were electrospun onto chitosan scaffolds to produce bilayer nanofibrous scaffolds (GC/L/C). The wounds treated with GC/L/C exhibited a higher recovery rate and transforming growth factor-beta (TGF-β) expression in Western blot assays. The decreased levels of pro-inflammatory markers, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), provided evidence for the anti-inflammatory effects of GC/L/C treatment. Chronic wounds treated with GC/L/C achieved better performance with a 58 ± 7% increase in recovery rate on the seventh day. Based on its anti-inflammatory and wound-healing effects, the GC/L/C bilayer nanofibrous scaffolds can be potential materials for chronic wound treatment. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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13 pages, 3648 KiB

Open AccessArticle

Human Adipose-Derived Stem Cell Secreted Extracellular Matrix Incorporated into Electrospun Poly(Lactic-co-Glycolic Acid) Nanofibrous Dressing for Enhancing Wound Healing

by Kao-Chun Tang, Kai-Chiang Yang, Che-Wei Lin, Yi-Kai Chen, Ting-Yu Lu, Hsien-Yeh Chen, Nai-Chen Cheng and Jiashing Yu

Polymers 2019, 11(10), 1609; https://doi.org/10.3390/polym11101609 - 3 Oct 2019

Cited by 30 | Viewed by 3990

Abstract

Wound dressing, which prevents dehydration and provides a physical barrier against infection to wound beds, can improve wound healing. The interactions between extracellular matrix (ECM) and growth factors is critical to the healing process. Electrospun nanofibers are promising templates for wound dressings due to the structure similarity to ECM of skin. Otherwise, the ECM secreted by human adipose-derived stem cells (hASCs) is rich in growth factors known to enhance wound healing. Accordingly, we propose that the PLGA nanofibrous template incorporated with hASCs-secreted ECM may enhance wound healing. In this study, PLGA nanofibrous matrixes with an aligned or a random structure were prepared by electrospinning. Human ASCs cultured on the aligned matrix had a better viability and produced a larger amount of ECM relative to that of random one. After 7 days’ cultivation, the hASCs on aligned PLGA substrates underwent decellularization to fabricate cECM/PLGA dressings. By using immunohistochemical staining against F-actin and cell nucleus, the removal of cellular components was verified. However, the type I collagen and laminin were well preserved on the cECM/PLGA nanofibrous matrixes. In addition, this substrate was hydrophilic, with appropriate mechanical strength to act as a wound dressing. The L929 fibroblasts had good activity, survival and proliferation on the cECM/PLGA meshes. In addition, the cECM/PLGA nanofibrous dressings improved the wound healing of surgically created full-thickness skin excision in a mouse model. This hASCs-secreted ECM incorporated into electrospun PLGA nanofibrous could be a promising dressing for enhancing wound healing. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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10 pages, 1693 KiB

Open AccessArticle

Vapor-Deposited Reactive Coating with Chemically and Topographically Erasable Properties

by Yu-Chih Chiang, Cuei-Ping Ho, Yin-Lin Wang, Po-Chun Chen, Peng-Yuan Wang and Hsien-Yeh Chen

Polymers 2019, 11(10), 1595; https://doi.org/10.3390/polym11101595 - 29 Sep 2019

Cited by 5 | Viewed by 2610

Abstract

An erasable coating was prepared to modify material surfaces with accessibilities, including specific conjugation, elimination of the conjugated chemistry/function, and the reactivation of a second new chemistry/function. The coating was realized based on a vapor-deposited functional poly-p-xylylene coating composed of an integrated 3-((3-methylamido)-disulfanyl)propanoic acid functional group, resulting in not only chemical reactivity, but also a disulfide interchange mechanism. Mechanically, the coating was robust in terms of the thermal stability and adhesive property on a variety of substrate materials. Chemically, the anchoring site of carboxylic acid was accessible for specific conjugation, and a disulfide bridge moiety was used to disengage already installed functions/properties. In addition, the homogeneous nature of the vapor-phased coating technique is known for its morphology/thickness and distribution of the functional moiety, which allowed precision to address the installation or erasure of functions and properties. Characterization of the precisely confined hydrophilic/hydrophobic wetting property and the alternating reversibility of this wetting property on the same surface was achieved. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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14 pages, 7835 KiB

Open AccessArticle

Fluorinated Montmorillonite Composite Resin as a Dental Pit and Fissure Sealant

by Keng-Yuan Li, Cheng-Chia Tsai, Chih-Hsiang Fang, Yin-Lin Wang, Feng-Huei Lin and Chun-Pin Lin

Polymers 2019, 11(10), 1535; https://doi.org/10.3390/polym11101535 - 20 Sep 2019

Cited by 13 | Viewed by 3353

Abstract

Molar pits and fissures tend to be affected by caries due to cleaning difficulties. As such, the filling of pits and cracks with sealants is common to deter the onset of caries. However, current clinical practices rely on sealants that lack the ability to release and recharge fluoride ions. Thus, we herein report the development of a fluoride—montmorillonite nanocomposite resin that has the potential to provide sustained release of fluoride due to the strong adsorption of fluoride by montmorillonite. X-ray diffractometry, thermogravimetric analysis, and Fourier-transform infrared spectroscopy were employed to confirm the successful insertion of the polymer into the interlayer structure. The mechanical properties (viscosity, hardening depth, hardness, diametral tensile strength, flexural strength, and wear resistance) of the developed composite resin were then examined, and simulation of the oral environment demonstrated a good fluoride ion release and recharge ability for the effective prevention of dental caries. Finally, we demonstrated the non-cytotoxic nature of this material using the water-soluble tetrazolium salt (WST-1) test. We expect that the described fluoride-containing composite resin may become a new clinical option in the near future. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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16 pages, 3983 KiB

Open AccessArticle

Fluorescent Nanodiamonds Enable Long-Term Detection of Human Adipose-Derived Stem/Stromal Cells in an In Vivo Chondrogenesis Model Using Decellularized Extracellular Matrices and Fibrin Glue Polymer

by Yi-Chia Wu, Ya-Chin Wang, Wei-Ting Wang, Hui-Min David Wang, Hsin-Hung Lin, Long-Jyun Su, Yur-Ren Kuo, Chung-Sheng Lai, Mei-Ling Ho and John Yu

Polymers 2019, 11(9), 1391; https://doi.org/10.3390/polym11091391 - 23 Aug 2019

Cited by 9 | Viewed by 3507

Abstract

Clinically available materials, including allogeneic irradiated costal cartilage and fibrin glue polymer, were used as scaffolds for in vivo chondrogenic differentiation of human adipose-derived stem/stromal cells (hASCs) in the attempt to develop a more efficient treatment over current methods. Current studies include the use of growth-factor stimulation, tissue engineering, and biocompatible materials; however, most methods involve complicated processes and pose clinical limitations. In this report, the xenografts in the experimental group composed of a diced decellularized cartilage extracellular matrix (ECM), hASCs, and fibrin glue polymer were implanted into the subcutaneous layer of nude mice, and the results were compared with two groups of controls; one control group received implantation of decellularized cartilage ECM and fibrin glue polymer, and the other control group received implantation of hASCs mixed with fibrin glue polymer. To evaluate whether hASCs had in vivo chondrogenesis in the xenografts, hASCs were labeled with fluorescent nanodiamonds (FNDs), a biocompatible and photostable nanomaterial, to allow for long-term detection and histological analysis. Increased cellularity, glycosaminoglycan, and collagen deposition were found by the histological examination in the experimental group compared with control groups. With the background-free detection technique and time-gated fluorescence imaging, the numbers and locations of the FND-labeled hASCs could be detected by confocal microscopy. The chondrocyte-specific markers, such as aggrecan and type II collagen, were colocalized with cells containing signals of FNDs which indicated in vivo chondrogenesis of hASCs. Taken together, functional in vivo chondrogenesis of the hASCs could be achieved by clinically available decellularized cartilage ECM and fibrin glue polymer in the nude mice model without in vitro chondrogenic induction. The fluorescent signals of FNDs in hASCs can be detected in histological analysis, such as hematoxylin and eosin staining (H&E staining) without the interference of the autofluorescence. Our study may warrant future clinical applications of the combination of decellular cartilage ECM, fibrin glue polymer, and hASCs for cartilage repair. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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18 pages, 4717 KiB

Open AccessArticle

Ultrasound-Assisted Encapsulation of Sacha Inchi (Plukenetia volubilis Linneo.) Oil in Alginate-Chitosan Nanoparticles

by Mariela Elgegren, Suyeon Kim, Diego Cordova, Carla Silva, Jennifer Noro, Artur Cavaco-Paulo and Javier Nakamatsu

Polymers 2019, 11(8), 1245; https://doi.org/10.3390/polym11081245 - 27 Jul 2019

Cited by 30 | Viewed by 5635

Abstract

Sacha inchi oil is rich in essential and non-essential fatty acids and other types of bioactive agents like tocopherols and polyphenolic compounds, which are very well-known antioxidants. In this study, the encapsulation of sacha inchi oil in alginate (AL) and chitosan (CS) nanoparticles was achieved with the assistance of high-intensity ultrasound. Nanoemulsion is the most effective delivery and high stability system for lipophilic bioactive agents. Chitosan and surfactant concentrations were varied to study their effect on particle formulations. Size, zeta-potential, polydispersity, and stability of particles were determined in time to optimize the preparation conditions. Sacha inchi oil encapsulated in AL-CS nanoparticles showed a higher loading efficiency and stability for short and long periods compared with other vegetable oils such as olive and soybean. Also, because of the types of tocopherols present in sacha inchi oil (γ- and δ-tocopherols), a much higher antioxidant activity (95% of radical reduction in 15 min) was found in comparison with nanocapsules with olive oil, which contain α-tocopherols. The particles showed high efficiency of protein loading at high concentration of bovine serum albumin (BSA) and a low rate of leaching profiles in various testing media like simulated gastric and intestinal fluids with/without enzymes, that is, pepsin 0.1% (w/v) and pancreatin 0.1% (w/v), respectively. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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23 pages, 7132 KiB

Open AccessArticle

Dual Responsive Polymersomes for Gold Nanorod and Doxorubicin Encapsulation: Nanomaterials with Potential Use as Smart Drug Delivery Systems

by Melissa DiazDuarte-Rodriguez, Norma A. Cortez-Lemus, Angel Licea-Claverie, Jacob Licea-Rodriguez and Eugenio R. Méndez

Polymers 2019, 11(6), 939; https://doi.org/10.3390/polym11060939 - 30 May 2019

Cited by 25 | Viewed by 5241

Abstract

In the present study, poly(ethylene glycol)-b-poly(N,N-diethylaminoethyl methacrylate) (PEG-b-PDEAEM) amphiphilic block copolymers were synthetized by reversible addition-fragmentation chain transfer (RAFT) polymerization using two different macro chain transfer agents containing PEG of 2000 and 5000 g/mol and varying the length of the PDEAEM segment. From the obtained block copolymers, polymersome type nanometric aggregates were obtained by two different techniques. By direct dispersion, particle diameters around 200 nm were obtained, while by solvent exchange using THF and water, the obtained diameters were around 100 nm. These block copolymers were used to encapsulate gold nanorods and doxorubicin (DOX) with good efficiencies to obtain nanomaterials with potential use as dual stimuli-sensitive drug delivery systems for combined anticancer therapies. Drug delivery studies showed that the release rate of DOX was accelerated when the pH was lowered from 7.4 to 5.8 and also when the systems were irradiated with a NIR laser at pH 7.4. The combination of lower pH and near infrared (NIR) irradiation resulted in higher drug release only in the case of polymersomes with lower molecular weight PEG. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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13 pages, 2441 KiB

Open AccessArticle

Dual-responsive Gemini Micelles for Efficient Delivery of Anticancer Therapeutics

by Young In Choi, Eun-sook Choi, Kwan Ho Mun, Se Guen Lee, Sung Jun Lee, Sang Won Jeong, Seung Woo Lee and Hyun-Chul Kim

Polymers 2019, 11(4), 604; https://doi.org/10.3390/polym11040604 - 2 Apr 2019

Cited by 3 | Viewed by 3152

Abstract

Polymeric micelles as drug delivery vehicles are popular owing to several advantages. In this study, a gemini amphiphile (gemini mPEG-Cys-PMT) consisting of hydrophilic poly(ethylene glycol) and hydrophobic poly(methionine) with cystine disulfide spacer was synthesized and its micellar properties for thiol- or reactive oxygen species (ROS)-dependent intracellular drug delivery were described. The cleavage of cystine linkage in a redox environment or the oxidation of methionine units in a ROS environment caused the destabilization of micelles. Such redox- or ROS-triggered micellar destabilization led to enhanced release of encapsulated doxorubicin (DOX) to induce cytotoxicity against cancer cells. Further, the therapeutic effects of the DOX-loaded micelles were demonstrated using the KB cell line. This study shows that thiol and ROS dual-responsive gemini micelles are promising platforms for nano-drug delivery in various cancer therapies. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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32 pages, 1301 KiB

Open AccessEditor’s ChoiceReview

Progress in Polymeric Nano-Medicines for Theranostic Cancer Treatment

by Imran Ali, Mosa Alsehli, Luciana Scotti, Marcus Tullius Scotti, Shang-Ting Tsai, Ruei-Siang Yu, Ming Fa Hsieh and Jung-Chih Chen

Polymers 2020, 12(3), 598; https://doi.org/10.3390/polym12030598 - 6 Mar 2020

Cited by 88 | Viewed by 8566

Abstract

Cancer is a life-threatening disease killing millions of people globally. Among various medical treatments, nano-medicines are gaining importance continuously. Many nanocarriers have been developed for treatment, but polymerically-based ones are acquiring importance due to their targeting capabilities, biodegradability, biocompatibility, capacity for drug loading and long blood circulation time. The present article describes progress in polymeric nano-medicines for theranostic cancer treatment, which includes cancer diagnosis and treatment in a single dosage form. The article covers the applications of natural and synthetic polymers in cancer diagnosis and treatment. Efforts were also made to discuss the merits and demerits of such polymers; the status of approved nano-medicines; and future perspectives. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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27 pages, 7429 KiB

Open AccessReview

Recent Advances in Polymeric Nanocomposites of Metal-Organic Frameworks (MOFs)

by Jun Zhong, Ranjith Kumar Kankala, Shi-Bin Wang and Ai-Zheng Chen

Polymers 2019, 11(10), 1627; https://doi.org/10.3390/polym11101627 - 9 Oct 2019

Cited by 23 | Viewed by 9883

Abstract

Recently, metal-organic frameworks (MOFs) have garnered enormous attention from researchers owing to their superior physicochemical properties, which are of particular interest in various fields such as catalysis and the diverse areas of biomedicine. Despite their position in the utilization for various applications compared to other innovative nanocarriers such as dendrimers and mesoporous silica nanoparticles (MSNs), in terms of advantageous physicochemical attributes, as well as attractive textural properties, ease of characterization, and abundant surface chemistry for functionalization and other benefits, MOFs yet suffer from several issues such as poor degradability, which might lead to accumulation-induced biocompatibility risk. In addition, some of the MOFs suffer from a shortcoming of poor colloidal stability in the aqueous solution, hindering their applicability in diverse biomedical fields. To address these limitations, several advancements have been made to fabricate polymeric nanocomposites of MOFs for their utility in various biomedical fields. In this review, we aim to provide a brief emphasis on various organic polymers used for coating over MOFs to improve their physicochemical attributes considering a series of recently reported intriguing studies. Finally, we summarize with perspectives. Full article

(This article belongs to the Special Issue Polymeric Colloidal Materials for Biomedical Applications)

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