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Polymers
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Smart Polymeric Systems as Drug Delivery Carriers
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Smart Polymeric Systems as Drug Delivery Carriers

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Biobased and Biodegradable Polymers".

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 28266

Special Issue Editor

Dr. Anamarija Rogina

E-Mail Website
Guest Editor
Faculty of Chemical Engineering and Technology, University of Zagreb, Zagreb, Croatia
Interests: biodegradable polymers; chitosan; hydrogels; scaffolds; biomaterials; bone tissue engineering; materials characterization

Special Issue Information

Dear Colleagues,

This Special Issue is devoted to polymer-based materials suitable as functional vehicles for drugs. As candidates for drug delivery application, materials must be biocompatible, biodegradable, nonimmunogenic and nontoxic. One of the major concerns in systematic drug administration is the interaction of drug with healthy organs and tissues, thus increasing the risk of toxicity and adverse drug effects. The new approach for polymeric drug vehicles includes intelligent drug delivery systems, i.e., stimuli-responsive drug carriers and systems with feedback-regulated drug release. While being administrated, drug is released under specific stimulus at targeted site. Thermo-, pH, electrical or magnetic responsive drug delivery systems are being investigated as potential candidates for sustained and controllable drug release, including liposomes, nanogels, nanocapsules, hydrogel beads, micelles, and so on. Still, there are challenges to overcome: the protection of drug from enzymes, the poor permeability of some tissues and low access to the targeted sites.

This Special Issue includes both recent original research and review articles covering topics from synthesis and characterization to biological validation of polymeric materials applied as potential drug delivery systems.

Dr. Anamarija Rogina
Guest Editor

Manuscript Submission Information

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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

  • hydrogels
  • biodegradable polymers
  • liposomes
  • encapsulation
  • drug delivery
  • self-assembled hydrogels
  • nanogels
  • bioinstructive microparticles
  • injectable hydrogels
  • micelles

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Published Papers (7 papers)

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Research

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14 pages, 3595 KiB  
Article
Chitosan-Boric Acid Scaffolds for Doxorubicin Delivery in the Osteosarcoma Treatment
by Luka Dornjak, Marin Kovačić, Karla Ostojić, Ange Angaits, Joanna Szpunar, Inga Urlić and Anamarija Rogina
Polymers 2022, 14(21), 4753; https://doi.org/10.3390/polym14214753 - 6 Nov 2022
Cited by 4 | Viewed by 2431
Abstract
Biologically compatible chitosan-based scaffolds have been considered a promising platform for tissue regeneration, tumor treatment, and targeted drug delivery. Chitosan-based scaffolds can be utilized as pH-sensitive drug carriers with targeted drug delivery resulting in less invasive tumor treatments. Further improvement with bioactive ions, [...] Read more.
Biologically compatible chitosan-based scaffolds have been considered a promising platform for tissue regeneration, tumor treatment, and targeted drug delivery. Chitosan-based scaffolds can be utilized as pH-sensitive drug carriers with targeted drug delivery resulting in less invasive tumor treatments. Further improvement with bioactive ions, such as borate ions, can result in the dual functionality of chitosan carriers provided by simultaneous antitumor efficacy and tissue regeneration. Here, boric acid-containing crosslinked chitosan scaffolds were prepared as delivery systems of doxorubicin, a chemotherapy drug used in the treatment of osteosarcoma. The encapsulation of boric acid was indicated by FTIR spectroscopy, while the ICP-MS analysis indicated the rapid release of boron in phosphate buffer (pH 6.0) and phosphate-buffered saline solution (pH 7.4). The obtained chitosan-boric acid scaffolds exhibit a highly porous and interconnected structure responsible for high swelling capacity, while enzymatic degradation indicated good scaffolds stability during four weeks of incubation at pH 6.0 and 7.4. Furthermore, the release of doxorubicin investigated in phosphate buffers indicated lower doxorubicin concentrations at pH 7.4 with respect to pH 6.0. Finally, the cytotoxicity of prepared doxorubicin-encapsulated scaffolds was evaluated on human sarcoma cells indicating the scaffolds’ potential as cytostatic agents. Full article
(This article belongs to the Special Issue Smart Polymeric Systems as Drug Delivery Carriers)
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16 pages, 2857 KiB  
Article
Cytotoxicity and Genotoxicity of Azobenzene-Based Polymeric Nanocarriers for Phototriggered Drug Release and Biomedical Applications
by Maritza Londoño-Berrío, Sandra Pérez-Buitrago, Isabel Cristina Ortiz-Trujillo, Lina M. Hoyos-Palacio, Luz Yaneth Orozco, Lucelly López, Diana G. Zárate-Triviño, John A. Capobianco and Pedro Mena-Giraldo
Polymers 2022, 14(15), 3119; https://doi.org/10.3390/polym14153119 - 31 Jul 2022
Cited by 5 | Viewed by 2706
Abstract
Drug nanoencapsulation increases the availability, pharmacokinetics, and concentration efficiency for therapeutic regimes. Azobenzene light-responsive molecules experience a hydrophobicity change from a polar to an apolar tendency by trans–cis photoisomerization upon UV irradiation. Polymeric photoresponse nanoparticles (PPNPs) based on azobenzene compounds and biopolymers such [...] Read more.
Drug nanoencapsulation increases the availability, pharmacokinetics, and concentration efficiency for therapeutic regimes. Azobenzene light-responsive molecules experience a hydrophobicity change from a polar to an apolar tendency by trans–cis photoisomerization upon UV irradiation. Polymeric photoresponse nanoparticles (PPNPs) based on azobenzene compounds and biopolymers such as chitosan derivatives show prospects of photodelivering drugs into cells with accelerated kinetics, enhancing their therapeutic effect. PPNP biocompatibility studies detect the safe concentrations for their administration and reduce the chance of side effects, improving the effectiveness of a potential treatment. Here, we report on a PPNP biocompatibility evaluation of viability and the first genotoxicity study of azobenzene-based PPNPs. Cell line models from human ventricular cardiomyocytes (RL14), as well as mouse fibroblasts (NIH3T3) as proof of concept, were exposed to different concentrations of azobenzene-based PPNPs and their precursors to evaluate the consequences on mitochondrial metabolism (MTT assay), the number of viable cells (trypan blue exclusion test), and deoxyribonucleic acid (DNA) damage (comet assay). Lethal concentrations of 50 (LC50) of the PPNPs and their precursors were higher than the required drug release and synthesis concentrations. The PPNPs affected the cell membrane at concentrations higher than 2 mg/mL, and lower concentrations exhibited lesser damage to cellular genetic material. An azobenzene derivative functionalized with a biopolymer to assemble PPNPs demonstrated biocompatibility with the evaluated cell lines. The PPNPs encapsulated Nile red and dofetilide separately as model and antiarrhythmic drugs, respectively, and delivered upon UV irradiation, proving the phototriggered drug release concept. Biocompatible PPNPs are a promising technology for fast drug release with high cell interaction opening new opportunities for azobenzene biomedical applications. Full article
(This article belongs to the Special Issue Smart Polymeric Systems as Drug Delivery Carriers)
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20 pages, 3909 KiB  
Article
Development of Carboxymethyl Chitosan Nanoparticles Prepared by Ultrasound-Assisted Technique for a Clindamycin HCl Carrier
by Tanpong Chaiwarit, Sarana Rose Sommano, Pornchai Rachtanapun, Nutthapong Kantrong, Warintorn Ruksiriwanich, Mont Kumpugdee-Vollrath and Pensak Jantrawut
Polymers 2022, 14(9), 1736; https://doi.org/10.3390/polym14091736 - 24 Apr 2022
Cited by 12 | Viewed by 3233
Abstract
Polymeric nanoparticles are one method to modify the drug release of small hydrophilic molecules. In this study, clindamycin HCl was used as a model drug loaded in carboxymethyl chitosan nanoparticles cross-linked with Ca2+ ions (CMCS-Ca2+). The ultrasonication with experimental design [...] Read more.
Polymeric nanoparticles are one method to modify the drug release of small hydrophilic molecules. In this study, clindamycin HCl was used as a model drug loaded in carboxymethyl chitosan nanoparticles cross-linked with Ca2+ ions (CMCS-Ca2+). The ultrasonication with experimental design was used to produce CMCS-Ca2+ nanoparticles loading clindamycin HCl. The model showed that the size of nanoparticles decreased when amplitude and time increased. The nanoparticle size of 318.40 ± 7.56 nm, decreased significantly from 543.63 ± 55.07 nm (p < 0.05), was obtained from 75% of amplitude and 180 s of time, which was one of the optimal conditions. The clindamycin loading content in this condition was 34.68 ± 2.54%. The drug content in nanoparticles showed an inverse relationship with the size of the nanoparticles. The sodium carboxymethylcellulose film loading clindamycin HCl nanoparticles exhibited extended release with 69.88 ± 2.03% drug release at 60 min and a gradual increase to 94.99 ± 4.70% at 24 h, and demonstrated good antibacterial activity against S. aureus and C. acne with 40.72 ± 1.23 and 48.70 ± 1.99 mm of the zone of inhibition at 24 h, respectively. Thus, CMCS-Ca2+ nanoparticles produced by the ultrasound-assisted technique could be a potential delivery system to modify the drug release of small hydrophilic antibiotics. Full article
(This article belongs to the Special Issue Smart Polymeric Systems as Drug Delivery Carriers)
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26 pages, 5206 KiB  
Article
Biocompatible Nanoparticles Based on Amphiphilic Random Polypeptides and Glycopolymers as Drug Delivery Systems
by Natalia Zashikhina, Mariia Levit, Anatoliy Dobrodumov, Sergey Gladnev, Antonina Lavrentieva, Tatiana Tennikova and Evgenia Korzhikova-Vlakh
Polymers 2022, 14(9), 1677; https://doi.org/10.3390/polym14091677 - 20 Apr 2022
Cited by 12 | Viewed by 2968
Abstract
In this research, the development and investigation of novel nanoobjects based on biodegradable random polypeptides and synthetic non-degradable glycopolymer poly(2-deoxy-2-methacrylamido-d-glucose) were proposed as drug delivery systems. Two different approaches have been applied for preparation of such nanomaterials. The first one includes [...] Read more.
In this research, the development and investigation of novel nanoobjects based on biodegradable random polypeptides and synthetic non-degradable glycopolymer poly(2-deoxy-2-methacrylamido-d-glucose) were proposed as drug delivery systems. Two different approaches have been applied for preparation of such nanomaterials. The first one includes the synthesis of block-random copolymers consisting of polypeptide and glycopolymer and capable of self-assembly into polymer particles. The synthesis of copolymers was performed using sequential reversible addition-fragmentation chain transfer (RAFT) and ring-opening polymerization (ROP) techniques. Amphiphilic poly(2-deoxy-2-methacrylamido-d-glucose)-b-poly(l-lysine-co-l-phenylalanine) (PMAG-b-P(Lys-co-Phe)) copolymers were then used for preparation of self-assembled nanoparticles. Another approach for the formation of polypeptide-glycopolymer particles was based on the post-modification of preformed polypeptide particles with an oxidized glycopolymer. The conjugation of the polysaccharide on the surface of the particles was achieved by the interaction of the aldehyde groups of the oxidized glycopolymer with the amino groups of the polymer on particle surface, followed by the reduction of the formed Schiff base with sodium borohydride. A comparative study of polymer nanoparticles developed with its cationic analogues based on random P(Lys-co-d-Phe), as well as an anionic one—P(Lys-co-d-Phe) covered with heparin––was carried out. In vitro antitumor activity of novel paclitaxel-loaded PMAG-b-P(Lys-co-Phe)-based particles towards A549 (human lung carcinoma) and MCF-7 (human breast adenocarcinoma) cells was comparable to the commercially available Paclitaxel-LANS. Full article
(This article belongs to the Special Issue Smart Polymeric Systems as Drug Delivery Carriers)
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22 pages, 4740 KiB  
Article
One-Pot Synthesis of Amphiphilic Biopolymers from Oxidized Alginate and Self-Assembly as a Carrier for Sustained Release of Hydrophobic Drugs
by Zhaowen Liu, Xiuqiong Chen, Zhiqin Huang, Hongcai Wang, Shirui Cao, Chunyang Liu, Huiqiong Yan and Qiang Lin
Polymers 2022, 14(4), 694; https://doi.org/10.3390/polym14040694 - 11 Feb 2022
Cited by 16 | Viewed by 2837
Abstract
In this paper, we developed an organic solvent-free, eco-friendly, simple and efficient one-pot approach for the preparation of amphiphilic conjugates (Ugi-OSAOcT) by grafting octylamine (OCA) to oxidized sodium alginate (OSA). The optimum reaction parameters that were obtained based on the degree of substitution [...] Read more.
In this paper, we developed an organic solvent-free, eco-friendly, simple and efficient one-pot approach for the preparation of amphiphilic conjugates (Ugi-OSAOcT) by grafting octylamine (OCA) to oxidized sodium alginate (OSA). The optimum reaction parameters that were obtained based on the degree of substitution (DS) of Ugi-OSAOcT were a reaction time of 12 h, a reaction temperature of 25 °C and a molar ratio of 1:2.4:3:3.3 (OSA:OCA:HAc:TOSMIC), respectively. The chemical structure and composition were characterized by Fourier transform infrared spectroscopy (FTIR), 1H nuclear magnetic resonance (1H NMR), X-ray diffraction (XRD), thermogravimetry analyser (TGA), gel permeation chromatography (GPC) and elemental analysis (EA). It was found that the Ugi-OSAOcT conjugates with a CMC value in the range of 0.30–0.085 mg/mL could self-assemble into stable and spherical micelles with a particle size of 135.7 ± 2.4–196.5 ± 3.8 nm and negative surface potentials of −32.8 ± 0.4–−38.2 ± 0.8 mV. Furthermore, ibuprofen (IBU), which served as a model poorly water-soluble drug, was successfully incorporated into the Ugi-OSAOcT micelles by dialysis method. The drug loading capacity (%DL) and encapsulation efficiency (%EE) of the IBU-loaded Ugi-OSAOcT micelles (IBU/Ugi-OSAOcT = 3:10) reached as much as 10.9 ± 0.4–14.6 ± 0.3% and 40.8 ± 1.6–57.2 ± 1.3%, respectively. The in vitro release study demonstrated that the IBU-loaded micelles had a sustained and pH-responsive drug release behavior. In addition, the DS of the hydrophobic segment on an OSA backbone was demonstrated to have an important effect on IBU loading and drug release behavior. Finally, the in vitro cytotoxicity assay demonstrated that the Ugi-OSAOcT conjugates exhibited no significant cytotoxicity against RAW 264.7 cells up to 1000 µg/mL. Therefore, the amphiphilic Ugi-OSAOcT conjugates synthesized by the green method exhibited great potential to load hydrophobic drugs, acting as a promising nanocarrier capable of responding to pH for sustained release of hydrophobic drugs. Full article
(This article belongs to the Special Issue Smart Polymeric Systems as Drug Delivery Carriers)
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Review

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20 pages, 1007 KiB  
Review
Intravitreal Injectable Hydrogels for Sustained Drug Delivery in Glaucoma Treatment and Therapy
by Kassahun Alula Akulo, Terin Adali, Mthabisi Talent George Moyo and Tulin Bodamyali
Polymers 2022, 14(12), 2359; https://doi.org/10.3390/polym14122359 - 10 Jun 2022
Cited by 18 | Viewed by 3579
Abstract
Glaucoma is extensively treated with topical eye drops containing drugs. However, the retention time of the loaded drugs and the in vivo bioavailability of the drugs are highly influenced before reaching the targeted area sufficiently, due to physiological and anatomical barriers of the [...] Read more.
Glaucoma is extensively treated with topical eye drops containing drugs. However, the retention time of the loaded drugs and the in vivo bioavailability of the drugs are highly influenced before reaching the targeted area sufficiently, due to physiological and anatomical barriers of the eye, such as rapid nasolacrimal drainage. Poor intraocular penetration and frequent administration may also cause ocular cytotoxicity. A novel approach to overcome these drawbacks is the use of injectable hydrogels administered intravitreously for sustained drug delivery to the target site. These injectable hydrogels are used as nanocarriers to intimately interact with specific diseased ocular tissues to increase the therapeutic efficacy and drug bioavailability of the anti-glaucomic drugs. The human eye is very delicate, and is sensitive to contact with any foreign body material. However, natural biopolymers are non-reactive, biocompatible, biodegradable, and lack immunogenic and inflammatory responses to the host whenever they are incorporated in drug delivery systems. These favorable biomaterial properties have made them widely applicable in biomedical applications, with minimal adversity. This review highlights the importance of using natural biopolymer-based intravitreal hydrogel drug delivery systems for glaucoma treatment over conventional methods. Full article
(This article belongs to the Special Issue Smart Polymeric Systems as Drug Delivery Carriers)
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20 pages, 582 KiB  
Review
Natural-Based Biomaterial for Skin Wound Healing (Gelatin vs. Collagen): Expert Review
by Ruth Naomi, Hasnah Bahari, Pauzi Muhd Ridzuan and Fezah Othman
Polymers 2021, 13(14), 2319; https://doi.org/10.3390/polym13142319 - 14 Jul 2021
Cited by 105 | Viewed by 9225
Abstract
Collagen (Col) and gelatin are most extensively used in various fields, particularly in pharmaceuticals and therapeutics. Numerous researchers have proven that they are highly biocompatible to human tissues, exhibit low antigenicity and are easy to degrade. Despite their different sources both Col and [...] Read more.
Collagen (Col) and gelatin are most extensively used in various fields, particularly in pharmaceuticals and therapeutics. Numerous researchers have proven that they are highly biocompatible to human tissues, exhibit low antigenicity and are easy to degrade. Despite their different sources both Col and gelatin have almost the same effects when it comes to wound healing mechanisms. Considering this, the bioactivity and biological effects of both Col and gelatin have been, and are being, constantly investigated through in vitro and in vivo assays to obtain maximum outcomes in the future. With regard to their proven nutritional values as sources of protein, Col and gelatin products exert various possible biological activities on cells in the extracellular matrix (ECM). In addition, a vast number of novel Col and gelatin applications have been discovered. This review compared Col and gelatin in terms of their structures, sources of derivatives, physicochemical properties, results of in vitro and in vivo studies, their roles in wound healing and the current challenges in wound healing. Thus, this review provides the current insights and the latest discoveries on both Col and gelatin in their wound healing mechanisms. Full article
(This article belongs to the Special Issue Smart Polymeric Systems as Drug Delivery Carriers)
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