Polymer Therapeutics: From Synthesis to Biomedical Applications

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

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 20897

Special Issue Editors

Departamento de Química Inorgánica, Orgánica y Bioquímica, Universidad de Castilla-La Mancha, Facultad de Farmacia, Campus Universitario de Albacete, 02071 Albacete, Spain
Interests: polymeric nanoparticles; antibody conjugate nanoparticles; breast cancer; biodegradable polymers; metallodrugs
Special Issues, Collections and Topics in MDPI journals
Dapartamento de Química-Física, Facultad de Farmacia, Centro Regional de Investigaciones Biomédicas, Universidad de Castilla-La Mancha, 02071 Albacete, Spain
Interests: physical chemistry; photonics; time resolved fluorescence spectroscopy; fluorescence microscopy; nanotechnology; cancer; nanomedicine; biosensors
Special Issues, Collections and Topics in MDPI journals
Netherlands Organisation for Scientific Research (NWO), DUBBLE@ESRF, BP CS 40220, 38043 Grenoble, France
Interests: supramolecular chemistry; polymer processing; biopolymers; structure-properties relationship; x-ray scattering; SAXS/WAXS; soft matter; polymer physics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The intimate relationship between molecular design and polymer applications has been largely exploited to attain functional materials with targeted responsive properties upon specific external stimuli. Particularly, the synthesis of biocompatible polymeric systems with biomedical and pharmaceutical applications is a challenging task that requires complex molecular architectures featuring ambivalent properties to efficiently fulfil therapeutic function and smart drug administration while retaining the pharmaceutical activity at industrial processing conditions.

Primarily, the specific drug uptake and controlled therapeutic release are harnessed from both supramolecular concepts and physicochemical phenomena to entrap the therapeutic agent with concepts such as host/guest molecular recognition and binding and the posterior drug release by various mechanisms assisted by biodegradation with external local physicochemical conditions.

Likewise, therapeutic polymers emerge as polymers with pharmaceutical and biomedical applications. The definition encompasses polymeric molecules that are naturally pharmaceutically active, polymers conjugated with the drug or with biomacromolecules such as proteins, polymeric nanoparticles or polymeric micellar systems, up to targeted polymeric systems conjugated with antibodies, tissue engineering, and polymers in orthopedic implants.

Herein, the current advances in the state of the art of novel therapeutic polymers are highlighted from the design, synthesis, physicochemical characterization, and processing to applicability in pharmacy and biomedicine.

Dr. Carlos Alonso-Moreno
Dr. Iván Bravo Pérez
Dr. Daniel Hermida-Merino
Guest Editors

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Keywords

  • polymer therapeutics
  • drug delivery systems
  • supramolecular smart polymeric systems
  • biomedicine
  • polymer processing
  • biodegradation

Published Papers (8 papers)

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Research

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23 pages, 9807 KiB  
Article
Composite Drug Delivery System Based on Amorphous Calcium Phosphate–Chitosan: An Efficient Antimicrobial Platform for Extended Release of Tetracycline
Pharmaceutics 2021, 13(10), 1659; https://doi.org/10.3390/pharmaceutics13101659 - 11 Oct 2021
Cited by 3 | Viewed by 2113
Abstract
One major warning emerging during the first worldwide combat against healthcare-associated infections concerns the key role of the surface in the storage and transfer of the virus. Our study is based on the laser coating of surfaces with an inorganic/organic composite mixture of [...] Read more.
One major warning emerging during the first worldwide combat against healthcare-associated infections concerns the key role of the surface in the storage and transfer of the virus. Our study is based on the laser coating of surfaces with an inorganic/organic composite mixture of amorphous calcium phosphate–chitosan–tetracycline that is able to fight against infectious agents, but also capable of preserving its activity for a prolonged time, up to several days. The extended release in simulated fluids of the composite mixture containing the drug (tetracycline) was demonstrated by mass loss and UV–VIS investigations. The drug release profile from our composite coatings proceeds via two stages: an initial burst release (during the first hours), followed by a slower evolution active for the next 72 h, and probably more. Optimized coatings strongly inhibit the growth of tested bacteria (Enterococcus faecalis and Escherichia coli), while the drug incorporation has no impact on the in vitro composite’s cytotoxicity, the coatings proving an excellent biocompatibility sustaining the normal development of MG63 bone-like cells. One may, therefore, consider that the proposed coatings’ composition can open the prospective of a new generation of antimicrobial coatings for implants, but also for nosocomial and other large area contamination prevention. Full article
(This article belongs to the Special Issue Polymer Therapeutics: From Synthesis to Biomedical Applications)
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21 pages, 5447 KiB  
Article
Hyaluronic Acid-Binding, Anionic, Nanoparticles Inhibit ECM Degradation and Restore Compressive Stiffness in Aggrecan-Depleted Articular Cartilage Explants
Pharmaceutics 2021, 13(9), 1503; https://doi.org/10.3390/pharmaceutics13091503 - 18 Sep 2021
Cited by 4 | Viewed by 2307
Abstract
Joint trauma results in the production of inflammatory cytokines that stimulate the secretion of catabolic enzymes, which degrade articular cartilage. Molecular fragments of the degraded articular cartilage further stimulate inflammatory cytokine production, with this process eventually resulting in post-traumatic osteoarthritis (PTOA). The loss [...] Read more.
Joint trauma results in the production of inflammatory cytokines that stimulate the secretion of catabolic enzymes, which degrade articular cartilage. Molecular fragments of the degraded articular cartilage further stimulate inflammatory cytokine production, with this process eventually resulting in post-traumatic osteoarthritis (PTOA). The loss of matrix component aggrecan occurs early in the progression of PTOA and results in the loss of compressive stiffness in articular cartilage. Aggrecan is highly sulfated, associates with hyaluronic acid (HA), and supports the compressive stiffness in cartilage. Presented here, we conjugated the HA-binding peptide GAHWQFNALTVRGSG (GAH) to anionic nanoparticles (hNPs). Nanoparticles conjugated with roughly 19 GAH peptides, termed 19 GAH-hNP, bound to HA in solution and increased the dynamic viscosity by 94.1% compared to an HA solution treated with unconjugated hNPs. Moreover, treating aggrecan-depleted (AD) cartilage explants with 0.10 mg of 19 GAH-hNP restored the cartilage compressive stiffness to healthy levels six days after a single nanoparticle treatment. Treatment of AD cartilage with 0.10 mg of 19 GAH-hNP inhibited the degradation of articular cartilage. Treated AD cartilage had 409% more collagen type II and 598% more GAG content than untreated-AD explants. The 19 GAH-hNP therapeutic slowed ECM degradation in AD cartilage explants, restored the compressive stiffness of damaged cartilage, and showed promise as a localized treatment for PTOA. Full article
(This article belongs to the Special Issue Polymer Therapeutics: From Synthesis to Biomedical Applications)
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20 pages, 6054 KiB  
Article
Enhancement of Rotator Cuff Healing with Farnesol-Impregnated Gellan Gum/Hyaluronic Acid Hydrogel Membranes in a Rabbit Model
Pharmaceutics 2021, 13(7), 944; https://doi.org/10.3390/pharmaceutics13070944 - 24 Jun 2021
Cited by 9 | Viewed by 2075
Abstract
Most rotator cuff (RC) tears occur at the bone–tendon interface and cause disability and pain. Farnesol, a sesquiterpene compound, can exert antioxidative and anti-inflammatory effects and promote collagen synthesis. In this rabbit model, either commercial SurgiWrap membrane or hydrogel membranes containing various compositions [...] Read more.
Most rotator cuff (RC) tears occur at the bone–tendon interface and cause disability and pain. Farnesol, a sesquiterpene compound, can exert antioxidative and anti-inflammatory effects and promote collagen synthesis. In this rabbit model, either commercial SurgiWrap membrane or hydrogel membranes containing various compositions of gellan gum, hyaluronic acid, and farnesol (hereafter GHF membranes) were applied to the tear site, and the repair of the cuff was examined 2 and 3 weeks afterward. The designed membranes swelled rapidly and adsorbed onto the tear site more readily and closely than the SurgiWrap membrane. The membranes degraded slowly and functioned as both a barrier and a vehicle of slow farnesol release during the repair period. Farnesol enhanced collagen production in myoblasts and tenocytes, and interleukin 6 and tumor necrosis factor α levels were modulated. Gross observations and histological examinations indicated that the GHF membranes impregnated with 4 mM farnesol resulted in superior RC repair. In sum, the slow release of farnesol from hydrogel membranes can be beneficial in the repair of RC injuries. Full article
(This article belongs to the Special Issue Polymer Therapeutics: From Synthesis to Biomedical Applications)
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18 pages, 2399 KiB  
Article
Effect of Poly(L-lysine) and Heparin Coatings on the Surface of Polyester-Based Particles on Prednisolone Release and Biocompatibility
Pharmaceutics 2021, 13(6), 801; https://doi.org/10.3390/pharmaceutics13060801 - 27 May 2021
Cited by 4 | Viewed by 2520
Abstract
A plethora of micro- and nanoparticle types are currently investigated for advanced ocular treatment due to improved drug retention times, higher bioavailability and better biocompatibility. Yet, comparative studies of both physicochemical and toxicological performance of these novel drug delivery systems are still rare. [...] Read more.
A plethora of micro- and nanoparticle types are currently investigated for advanced ocular treatment due to improved drug retention times, higher bioavailability and better biocompatibility. Yet, comparative studies of both physicochemical and toxicological performance of these novel drug delivery systems are still rare. Herein, poly(L-lactic acid)- and poly(ε-caprolactone)-based micro- and nanoparticles were loaded with prednisolone as a model drug. The physicochemical properties of the particles were varied with respect to their hydrophilicity and size as well as their charge and the effect on prednisolone release was evaluated. The particle biocompatibility was assessed by a two-tier testing strategy, combining the EpiOcularTM eye irritation test and bovine corneal opacity and permeability assay. The biodegradable polyelectrolyte corona on the particles’ surface determined the surface charge and the release rate, enabling prednisolone release for at least 30 days. Thereby, the prednisolone release process was mainly governed by molecular diffusion. Finally, the developed particle formulations were found to be nontoxic in the tested range of concentrations. Full article
(This article belongs to the Special Issue Polymer Therapeutics: From Synthesis to Biomedical Applications)
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12 pages, 2502 KiB  
Article
Synergistic Photothermal-Chemotherapy Based on the Use of Biomimetic Magnetic Nanoparticles
Pharmaceutics 2021, 13(5), 625; https://doi.org/10.3390/pharmaceutics13050625 - 28 Apr 2021
Cited by 15 | Viewed by 2099
Abstract
MamC-mediated biomimetic magnetic nanoparticles (BMNPs) have emerged as one of the most promising nanomaterials due to their magnetic features (superparamagnetic character and large magnetic moment per particle), their novel surface properties determined by MamC, their biocompatibility and their ability as magnetic hyperthermia agents. [...] Read more.
MamC-mediated biomimetic magnetic nanoparticles (BMNPs) have emerged as one of the most promising nanomaterials due to their magnetic features (superparamagnetic character and large magnetic moment per particle), their novel surface properties determined by MamC, their biocompatibility and their ability as magnetic hyperthermia agents. However, the current clinical application of magnetic hyperthermia is limited due to the fact that, in order to be able to reach an effective temperature at the target site, relatively high nanoparticle concentration, as well as high magnetic field strength and/or AC frequency are needed. In the present study, the potential of BMNPs to increase the temperature upon irradiation of a laser beam in the near infrared, at a wavelength at which tissues become partially transparent, is explored. Moreover, our results also demonstrate the synergy between photothermia and chemotherapy in terms of drug release and cytotoxicity, by using BMNPs functionalized with doxorubicin, and the effectiveness of this combination therapy against tumor cells in in vitro experiments. Therefore, the findings of the present study open the possibility of a novel, alternative approach to fight localized tumors. Full article
(This article belongs to the Special Issue Polymer Therapeutics: From Synthesis to Biomedical Applications)
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Review

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36 pages, 21874 KiB  
Review
Polylactide Perspectives in Biomedicine: From Novel Synthesis to the Application Performance
Pharmaceutics 2022, 14(8), 1673; https://doi.org/10.3390/pharmaceutics14081673 - 11 Aug 2022
Cited by 7 | Viewed by 2503
Abstract
The incessant developments in the pharmaceutical and biomedical fields, particularly, customised solutions for specific diseases with targeted therapeutic treatments, require the design of multicomponent materials with multifunctional capabilities. Biodegradable polymers offer a variety of tailored physicochemical properties minimising health adverse side effects at [...] Read more.
The incessant developments in the pharmaceutical and biomedical fields, particularly, customised solutions for specific diseases with targeted therapeutic treatments, require the design of multicomponent materials with multifunctional capabilities. Biodegradable polymers offer a variety of tailored physicochemical properties minimising health adverse side effects at a low price and weight, which are ideal to design matrices for hybrid materials. PLAs emerge as an ideal candidate to develop novel materials as are endowed withcombined ambivalent performance parameters. The state-of-the-art of use of PLA-based materials aimed at pharmaceutical and biomedical applications is reviewed, with an emphasis on the correlation between the synthesis and the processing conditions that define the nanostructure generated, with the final performance studies typically conducted with either therapeutic agents by in vitro and/or in vivo experiments or biomedical devices. Full article
(This article belongs to the Special Issue Polymer Therapeutics: From Synthesis to Biomedical Applications)
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27 pages, 8128 KiB  
Review
Stimuli Responsive Nitric Oxide-Based Nanomedicine for Synergistic Therapy
Pharmaceutics 2021, 13(11), 1917; https://doi.org/10.3390/pharmaceutics13111917 - 12 Nov 2021
Cited by 21 | Viewed by 3038
Abstract
Gas therapy has received widespread attention from the medical community as an emerging and promising therapeutic approach to cancer treatment. Among all gas molecules, nitric oxide (NO) was the first one to be applied in the biomedical field for its intriguing properties and [...] Read more.
Gas therapy has received widespread attention from the medical community as an emerging and promising therapeutic approach to cancer treatment. Among all gas molecules, nitric oxide (NO) was the first one to be applied in the biomedical field for its intriguing properties and unique anti-tumor mechanisms which have become a research hotspot in recent years. Despite the great progress of NO in cancer therapy, the non-specific distribution of NO in vivo and its side effects on normal tissue at high concentrations have impaired its clinical application. Therefore, it is important to develop facile NO-based nanomedicines to achieve the on-demand release of NO in tumor tissue while avoiding the leakage of NO in normal tissue, which could enhance therapeutic efficacy and reduce side effects at the same time. In recent years, numerous studies have reported the design and development of NO-based nanomedicines which were triggered by exogenous stimulus (light, ultrasound, X-ray) or tumor endogenous signals (glutathione, weak acid, glucose). In this review, we summarized the design principles and release behaviors of NO-based nanomedicines upon various stimuli and their applications in synergistic cancer therapy. We also discuss the anti-tumor mechanisms of NO-based nanomedicines in vivo for enhanced cancer therapy. Moreover, we discuss the existing challenges and further perspectives in this field in the aim of furthering its development. Full article
(This article belongs to the Special Issue Polymer Therapeutics: From Synthesis to Biomedical Applications)
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39 pages, 4406 KiB  
Review
Chitosan-Based Biocompatible Copolymers for Thermoresponsive Drug Delivery Systems: On the Development of a Standardization System
Pharmaceutics 2021, 13(11), 1876; https://doi.org/10.3390/pharmaceutics13111876 - 05 Nov 2021
Cited by 8 | Viewed by 2579
Abstract
Chitosan is a natural polysaccharide that is considered to be biocompatible, biodegradable and non-toxic. The polymer has been used in drug delivery applications for its positive charge, which allows for adhesion with and recognition of biological tissues via non-covalent interactions. In recent times, [...] Read more.
Chitosan is a natural polysaccharide that is considered to be biocompatible, biodegradable and non-toxic. The polymer has been used in drug delivery applications for its positive charge, which allows for adhesion with and recognition of biological tissues via non-covalent interactions. In recent times, chitosan has been used for the preparation of graft copolymers with thermoresponsive polymers such as poly-N-vinylcaprolactam (PNVCL) and poly-N-isopropylamide (PNIPAM), allowing the combination of the biodegradability of the natural polymer with the ability to respond to changes in temperature. Due to the growing interest in the utilization of thermoresponsive polymers in the biological context, it is necessary to increase the knowledge of the key principles of thermoresponsivity in order to obtain comparable results between different studies or applications. In the present review, we provide an overview of the basic principles of thermoresponsivity, as well as a description of the main polysaccharides and thermoresponsive materials, with a special focus on chitosan and poly-N-Vinyl caprolactam (PNVCL) and their biomedical applications. Full article
(This article belongs to the Special Issue Polymer Therapeutics: From Synthesis to Biomedical Applications)
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