Polymeric Carriers for Biomedical and Nanomedicine Application

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

Deadline for manuscript submissions: closed (20 November 2020) | Viewed by 35882

Special Issue Editors

LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Interests: cell culture; colloids; magnetic nanoparticles; marine polysaccharides; liposomes; lipid nanoparticles; photothermal therapy; polymeric nanoparticles
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Guest Editor
Associate Professor, LAQV, REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal
Interests: medicinal chemistry; infectious, inflammatory and cancer diseases; nanotechnology and nanodelivery; development of “smart” drug systems; biophysics and drug-membrane interactions
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We would like to invite you to contribute a full article, short communication, or review article to the Special Issue entitled “Polymeric Carriers for Biomedical and Nanomedicine Applications”, which is anticipated to include topics on synthetic and natural polymers as materials for drug delivery, such as nanoparticles and hydrogels, to elicit specific biological responses. Polymers contribute to the development of carriers to improve drug delivery in a targeted and sustainable manner, but also to the optimization of disease diagnostic tools. Several advances have been described in the application of polymers in the biomedical field given their special mechanical, physical, chemical, and biological characteristics. Unravelling the mechanism of action of these polymeric biomaterials in a biological context is also important to enhance their successful translation to clinical trials.

This Special Issue will focus on the development of polymeric delivery systems towards biomedical and nanomedicine applications as well as on understanding how such biomaterials interact under biological conditions. Contributions related to the advances in materials (e.g., functionalization, responsiveness), design and characterization, cellular interactions, and assessment using in vitro, ex vivo, and in vivo disease modes, and biomedical applications will provide knowledge on the polymer–biology interface. The topics are not limited to these studies and can cover all research areas concerning polymeric materials applied in the nanomedicine field.

We would very much appreciate if you would consider being one of our authors. We look forward to your contribution.

Dr. Sofia Lima
Prof. Salette Reis
Guest Editors

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Keywords

  • Biological barriers interaction
  • Biomedical devices
  • Controlled release
  • Drug delivery systems
  • Functional nanoparticles
  • Stimuli-responsiveness
  • Targeted systems

Published Papers (11 papers)

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Editorial

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4 pages, 182 KiB  
Editorial
Polymeric Carriers for Biomedical and Nanomedicine Application
by Sofia A. Costa Lima and Salette Reis
Polymers 2021, 13(8), 1261; https://doi.org/10.3390/polym13081261 - 13 Apr 2021
Cited by 1 | Viewed by 1366
Abstract
Polymeric carriers play a key role in modern biomedical and nanomedicine applications [...] Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)

Research

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25 pages, 10156 KiB  
Article
Encapsulation of the Natural Product Tyrosol in Carbohydrate Nanosystems and Study of Their Binding with ctDNA
by Antonella Rozaria Nefeli Pontillo, Evangelia Konstanteli, Maria M. Bairaktari and Anastasia Detsi
Polymers 2021, 13(1), 87; https://doi.org/10.3390/polym13010087 - 28 Dec 2020
Cited by 9 | Viewed by 2115
Abstract
Tyrosol, a natural product present in olive oil and white wine, possesses a wide range of bioactivity. The aim of this study was to optimize the preparation of nanosystems encapsulating tyrosol in carbohydrate matrices and the investigation of their ability to bind with [...] Read more.
Tyrosol, a natural product present in olive oil and white wine, possesses a wide range of bioactivity. The aim of this study was to optimize the preparation of nanosystems encapsulating tyrosol in carbohydrate matrices and the investigation of their ability to bind with DNA. The first encapsulation matrix of choice was chitosan using the ionic gelation method. The second matrix was β-cyclodextrin (βCD) using the kneading method. Coating of the tyrosol-βCD ICs with chitosan resulted in a third nanosystem with very interesting properties. Optimal preparation parameters of each nanosystem were obtained through two three-factor, three-level Box-Behnken experimental designs and statistical analysis of the results. Thereafter, the nanoparticles were evaluated for their physical and thermal characteristics using several techniques (DLS, NMR, FT-IR, DSC, TGA). The study was completed with the investigation of the impact of the encapsulation on the ability of tyrosol to bind to calf thymus DNA. The results revealed that tyrosol and all the studied systems bind to the minor groove of ctDNA. Tyrosol interacts with ctDNA via hydrogen bond formation, as predicted via molecular modeling studies and corroborated by the experiments. The tyrosol-chitosan nanosystem does not show any binding to ctDNA whereas the βCD inclusion complex shows analogous interaction with that of free tyrosol. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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10 pages, 1700 KiB  
Article
Poly(d,l-lactide-co-glycolide) (PLGA) Nanoparticles Loaded with Proteolipid Protein (PLP)—Exploring a New Administration Route
by Alexandre Ferreira Lima, Isabel R. Amado and Liliana R. Pires
Polymers 2020, 12(12), 3063; https://doi.org/10.3390/polym12123063 - 21 Dec 2020
Cited by 19 | Viewed by 2733
Abstract
The administration of specific antigens is being explored as a mean to re-establish immunological tolerance, namely in the context of multiple sclerosis (MS). PLP139-151 is a peptide of the myelin’s most abundant protein, proteolipid protein (PLP), which has been identified as a potent [...] Read more.
The administration of specific antigens is being explored as a mean to re-establish immunological tolerance, namely in the context of multiple sclerosis (MS). PLP139-151 is a peptide of the myelin’s most abundant protein, proteolipid protein (PLP), which has been identified as a potent tolerogenic molecule in MS. This work explored the encapsulation of the peptide into poly(lactide-co-glycolide) nanoparticles and its subsequent incorporation into polymeric microneedle patches to achieve efficient delivery of the nanoparticles and the peptide into the skin, a highly immune-active organ. Different poly(d,l-lactide-co-glycolide) (PLGA) formulations were tested and found to be stable and to sustain a freeze-drying process. The presence of trehalose in the nanoparticle suspension limited the increase in nanoparticle size after freeze-drying. It was shown that rhodamine can be loaded in PLGA nanoparticles and these into poly(vinyl alcohol)–poly(vinyl pyrrolidone) microneedles, yielding fluorescently labelled structures. The incorporation of PLP into the PLGA nanoparticles resulted in nanoparticles in a size range of 200 µm and an encapsulation efficiency above 20%. The release of PLP from the nanoparticles occurred in the first hours after incubation in physiological media. When loading the nanoparticles into microneedle patches, structures were obtained with 550 µm height and 180 µm diameter. The release of PLP was detected in PLP–PLGA.H20 nanoparticles when in physiological media. Overall, the results show that this strategy can be explored to integrate a new antigen-specific therapy in the context of multiple sclerosis, providing minimally invasive administration of PLP-loaded nanoparticles into the skin. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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11 pages, 1776 KiB  
Communication
An Investigation of the Influence of PEG 400 and PEG-6-Caprylic/Capric Glycerides on Dermal Delivery of Niacinamide
by Yanling Zhang, Majella E. Lane and David J. Moore
Polymers 2020, 12(12), 2907; https://doi.org/10.3390/polym12122907 - 04 Dec 2020
Cited by 19 | Viewed by 4360
Abstract
Polyethylene glycols (PEGs) and PEG derivatives are used in a range of cosmetic and pharmaceutical products. However, few studies have investigated the influence of PEGs and their related derivatives on skin permeation, especially when combined with other solvents. Previously, we reported niacinamide (NIA) [...] Read more.
Polyethylene glycols (PEGs) and PEG derivatives are used in a range of cosmetic and pharmaceutical products. However, few studies have investigated the influence of PEGs and their related derivatives on skin permeation, especially when combined with other solvents. Previously, we reported niacinamide (NIA) skin permeation from a range of neat solvents including propylene glycol (PG), Transcutol® P (TC), dimethyl isosorbide (DMI), PEG 400 and PEG 600. In the present work, binary and ternary systems composed of PEGs or PEG derivatives combined with other solvents were investigated for skin delivery of NIA. In vitro finite dose studies were conducted (5 μL/cm2) in porcine skin over 24 h. Higher skin permeation of NIA was observed for all vehicles compared to PEG 400. However, overall permeation for the binary and ternary systems was comparatively low compared with results for PG, TC and DMI. Interestingly, values for percentage skin retention of NIA for PEG 400:DMI and PEG 400:TC were significantly higher than values for DMI, TC and PG (p < 0.05). The findings suggest that PEG 400 may be a useful component of formulations for the delivery of actives to the skin rather than through the skin. Future studies will expand the range of vehicles investigated and also look at skin absorption and residence time of PEG 400 compared to other solvents. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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19 pages, 17495 KiB  
Article
Development and Evaluation of Polymeric Nanosponge Hydrogel for Terbinafine Hydrochloride: Statistical Optimization, In Vitro and In Vivo Studies
by Aditee Ghose, Bushra Nabi, Saleha Rehman, Shadab Md, Nabil A. Alhakamy, Osama A. A. Ahmad, Sanjula Baboota and Javed Ali
Polymers 2020, 12(12), 2903; https://doi.org/10.3390/polym12122903 - 03 Dec 2020
Cited by 21 | Viewed by 3039
Abstract
Terbinafine hydrochloride, although one of the prominent antifungal agents, suffers from low drug permeation owing to its hydrophobic nature. The approach of nanosponge formulation may thus help to resolve this concern. Thus, the present research was envisioned to fabricate the nanosponge hydrogel of [...] Read more.
Terbinafine hydrochloride, although one of the prominent antifungal agents, suffers from low drug permeation owing to its hydrophobic nature. The approach of nanosponge formulation may thus help to resolve this concern. Thus, the present research was envisioned to fabricate the nanosponge hydrogel of terbinafine hydrochloride for topical delivery since nanosponge augments the skin retentivity of the drug. The optimized formulation was obtained using Box Behnken Design. The dependent and independent process parameters were also determined wherein polyvinyl alcohol (%), ethylcellulose (%), and tween 80 (%) were taken as independent process parameters and particle size, polydispersity index (PDI), and entrapment efficiency (EE) were the dependent parameters. The nanosponge was then incorporated into the hydrogel and characterized. In-vitro drug release from the hydrogel was 90.20 ± 0.1% which was higher than the drug suspension and marketed formulation. In vitro permeation potential of the developed formulation through rat skin showed a flux of 0.594 ± 0.22 µg/cm2/h while the permeability coefficient was 0.059 ± 0.022 cm/s. Nanosponge hydrogel was evaluated for non-irritancy and antifungal activity against C. albicans and T. rubrum confirming the substantial outcome. Tape stripping studies exhibited ten times stripping off the skin quantified 85.6 ± 0.21 μg/cm2. The confocal analysis justified the permeation potential of the prepared hydrogel. The mean erythemal score was 0.0, confirming that the prepared hydrogel did not cause erythema or oedema. Therefore, based on results obtained, nanosponge hydrogel formulation is a potential carrier for efficient topical delivery of terbinafine hydrochloride. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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17 pages, 2420 KiB  
Article
Three-Step Synthesis of a Redox-Responsive Blend of PEG–block–PLA and PLA and Application to the Nanoencapsulation of Retinol
by Louise Van Gheluwe, Eric Buchy, Igor Chourpa and Emilie Munnier
Polymers 2020, 12(10), 2350; https://doi.org/10.3390/polym12102350 - 14 Oct 2020
Cited by 7 | Viewed by 2335
Abstract
Smart polymeric nanocarriers have been developed to deliver therapeutic agents directly to the intended site of action, with superior efficacy. Herein, a mixture of poly(lactide) (PLA) and redox-responsive poly(ethylene glycol)–block–poly(lactide) (PEG–block–PLA) containing a disulfide bond was synthesized in three [...] Read more.
Smart polymeric nanocarriers have been developed to deliver therapeutic agents directly to the intended site of action, with superior efficacy. Herein, a mixture of poly(lactide) (PLA) and redox-responsive poly(ethylene glycol)–block–poly(lactide) (PEG–block–PLA) containing a disulfide bond was synthesized in three steps. The nanoprecipitation method was used to prepare an aqueous suspension of polymeric nanocarriers with a hydrodynamic diameter close to 100 nm. Retinol, an anti-aging agent very common in cosmetics, was loaded into these smart nanocarriers as a model to measure their capacity to encapsulate and to protect a lipophilic active molecule. Retinol was encapsulated with a high efficiency with final loading close to 10% w/w. The stimuli-responsive behavior of these nanocarriers was demonstrated in vitro, in the presence of l-Glutathione, susceptible to break of disulfide bond. The toxicity was low on human keratinocytes in vitro and was mainly related to the active molecule. Those results show that it is not necessary to use 100% of smart copolymer in a nanosystem to obtain a triggered release of their content. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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16 pages, 3648 KiB  
Article
Characterization and Therapeutic Effect of a pH Stimuli Responsive Polymeric Nanoformulation for Controlled Drug Release
by Maria Victoria Cano-Cortes, Jose Antonio Laz-Ruiz, Juan Jose Diaz-Mochon and Rosario Maria Sanchez-Martin
Polymers 2020, 12(6), 1265; https://doi.org/10.3390/polym12061265 - 01 Jun 2020
Cited by 10 | Viewed by 2891
Abstract
Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with [...] Read more.
Despite the large number of polymeric nanodelivery systems that have been recently developed, there is still room for improvement in terms of therapeutic efficiency. Most reported nanodevices for controlled release are based on drug encapsulation, which can lead to undesired drug leakage with a consequent reduction in efficacy and an increase in systemic toxicity. Herein, we present a strategy for covalent drug conjugation to the nanodevice to overcome this drawback. In particular, we characterize and evaluate an effective therapeutic polymeric PEGylated nanosystem for controlled pH-sensitive drug release on a breast cancer (MDA-MB-231) and two lung cancer (A549 and H520) cell lines. A significant reduction in the required drug dose to reach its half maximal inhibitory concentration (IC50 value) was achieved by conjugation of the drug to the nanoparticles, which leads to an improvement in the therapeutic index by increasing the efficiency. The genotoxic effect of this nanodevice in cancer cells was confirmed by nucleus histone H2AX specific immunostaining. In summary, we successfully characterized and validated a pH responsive therapeutic polymeric nanodevice in vitro for controlled anticancer drug release. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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13 pages, 3015 KiB  
Article
Investigating Novel Syntheses of a Series of Unique Hybrid PLGA-Chitosan Polymers for Potential Therapeutic Delivery Applications
by Jason Thomas Duskey, Cecilia Baraldi, Maria Cristina Gamberini, Ilaria Ottonelli, Federica Da Ros, Giovanni Tosi, Flavio Forni, Maria Angela Vandelli and Barbara Ruozi
Polymers 2020, 12(4), 823; https://doi.org/10.3390/polym12040823 - 04 Apr 2020
Cited by 17 | Viewed by 4145
Abstract
Discovering new materials to aid in the therapeutic delivery of drugs is in high demand. PLGA, a FDA approved polymer, is well known in the literature to form films or nanoparticles that can load, protect, and deliver drug molecules; however, its incompatibility with [...] Read more.
Discovering new materials to aid in the therapeutic delivery of drugs is in high demand. PLGA, a FDA approved polymer, is well known in the literature to form films or nanoparticles that can load, protect, and deliver drug molecules; however, its incompatibility with certain drugs (due to hydrophilicity or charge repulsion interactions) limits its use. Combining PLGA or other polymers such as polycaprolactone with other safe and positively-charged molecules, such as chitosan, has been sought after to make hybrid systems that are more flexible in terms of loading ability, but often the reactions for polymer coupling use harsh conditions, films, unpurified products, or create a single unoptimized product. In this work, we aimed to investigate possible innovative improvements regarding two synthetic procedures. Two methods were attempted and analytically compared using nuclear magnetic resonance (NMR), fourier-transform infrared spectroscopy (FT-IR), and dynamic scanning calorimetry (DSC) to furnish pure, homogenous, and tunable PLGA-chitosan hybrid polymers. These were fully characterized by analytical methods. A series of hybrids was produced that could be used to increase the suitability of PLGA with previously non-compatible drug molecules. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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23 pages, 4869 KiB  
Article
A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design
by Hazem Abdul Kader Sabbagh, Samer Hasan Hussein-Al-Ali, Mohd Zobir Hussein, Zead Abudayeh, Rami Ayoub and Suha Mujahed Abudoleh
Polymers 2020, 12(4), 772; https://doi.org/10.3390/polym12040772 - 01 Apr 2020
Cited by 22 | Viewed by 3294
Abstract
The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (21 × 31 × 21) × 3 = 36 full factorial design (FFD) to [...] Read more.
The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (21 × 31 × 21) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl2) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl2 concentrations, whereas zeta potential depends only on the Alg and CaCl2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (−9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm−1, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model (R2 between 0.956–0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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14 pages, 2607 KiB  
Article
p47phox siRNA-Loaded PLGA Nanoparticles Suppress ROS/Oxidative Stress-Induced Chondrocyte Damage in Osteoarthritis
by Hyo Jung Shin, Hyewon Park, Nara Shin, Hyeok Hee Kwon, Yuhua Yin, Jeong-Ah Hwang, Song I Kim, Sang Ryong Kim, Sooil Kim, Yongbum Joo, Youngmo Kim, Jinhyun Kim, Jaewon Beom and Dong Woon Kim
Polymers 2020, 12(2), 443; https://doi.org/10.3390/polym12020443 - 13 Feb 2020
Cited by 40 | Viewed by 3925
Abstract
Osteoarthritis (OA) is the most common joint disorder that has had an increasing prevalence due to the aging of the population. Recent studies have concluded that OA progression is related to oxidative stress and reactive oxygen species (ROS). ROS are produced at low [...] Read more.
Osteoarthritis (OA) is the most common joint disorder that has had an increasing prevalence due to the aging of the population. Recent studies have concluded that OA progression is related to oxidative stress and reactive oxygen species (ROS). ROS are produced at low levels in articular chondrocytes, mainly by the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and ROS production and oxidative stress have been found to be elevated in patients with OA. The cartilage of OA-affected rat exhibits a significant induction of p47phox, a cytosolic subunit of the NADPH oxidase, similarly to human osteoarthritis cartilage. Therefore, this study tested whether siRNA p47phox that is introduced with poly (D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (p47phox si_NPs) can alleviate chondrocyte cell death by reducing ROS production. Here, we confirm that p47phox si_NPs significantly attenuated oxidative stress and decreased cartilage damage in mono-iodoacetate (MIA)-induced OA. In conclusion, these data suggest that p47phox si_NPs may be of therapeutic value in the treatment of osteoarthritis. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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Review

Jump to: Editorial, Research

18 pages, 1552 KiB  
Review
Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles
by Raquel G. D. Andrade, Bruno Reis, Benjamin Costas, Sofia A. Costa Lima and Salette Reis
Polymers 2021, 13(1), 88; https://doi.org/10.3390/polym13010088 - 28 Dec 2020
Cited by 23 | Viewed by 4711
Abstract
Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and [...] Read more.
Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications. Full article
(This article belongs to the Special Issue Polymeric Carriers for Biomedical and Nanomedicine Application)
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