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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (25 June 2019) | Viewed by 49811

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Prof. Dr. Ylenia Zambito

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Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Interests: controlled drug delivery systems; nanomedicine; nutraceutical products; thermosensitive hydrogels; ocular delivery; oral delivery; multifunctional chitosan derivatives; mucoadhesive nanoparticles
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Dr. Angela Fabiano

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Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Interests: mucoadhesive polymeric nanoparticulate systems; ocular and oral administration of drugs; nutraceutic; delivery systems of nutraceutical products; thermosensitive hydrogels; chitosan and its derivatives
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Anna Maria Piras

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Department of Pharmacy, University of Pisa, 56126 Pisa, Italy
Interests: nanomedicine; drug delivery; pharmaceutics and pharmaceutical technology; polymeric biomaterials; biodegradable polymers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is known that even slight physicochemical differences on the nanoparticle surface are reflected in significant biological differences concerning, e.g., cellular uptake, the biological processes regulating such an uptake, and nanoparticle biodistribution. Together with the surface features, nanoparticle size and shape are also known to affect cellular uptake and particle biodistribution. It appears thus to be promising to more deeply investigate and correlate these aspects to be able to modulate and promote selective cellular uptake, thus targeting the site of action, resulting in strong pharmacological activity with low systemic exposure.

Much interest has been focused on nanoparticulate release systems based on chitosan and its derivatives because of their good biocompatibility and effectiveness in releasing macromolecular drugs. The physicochemical surface properties of the nanoparticles based on chitosan conjugates depend on the functional groups that have been substituted on the polymer chains. The use of chitosan and its derivatives for the preparation of medicated nanoparticles will be the focus of the present Special Issue to derive some considerations regarding the structure–activity relationship.

Prof. Dr. Ylenia Zambito
Dr. Angela Fabiano
Dr. Anna Maria Piras
Guest Editors

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Keywords

Chitosan derivatives
Nanoparticulate drug delivery systems
Macromolecular drugs
Mucoadhesive nanoparticles
Mucopenetrating nanoparticles
Cells uptake

Related Special Issue

Chitosan-Based Systems for Pharmaceutical and Nutraceutical Applications in International Journal of Molecular Sciences (9 articles)

Published Papers (10 papers)

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Research

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14 pages, 2275 KiB

Open AccessArticle

Enhancing the Thermo-Stability and Anti-Biofilm Activity of Alginate Lyase by Immobilization on Low Molecular Weight Chitosan Nanoparticles

by Shangyong Li, Yanan Wang, Xiao Li, Beom Suk Lee, Samil Jung and Myeong-Sok Lee

Int. J. Mol. Sci. 2019, 20(18), 4565; https://doi.org/10.3390/ijms20184565 - 14 Sep 2019

Cited by 32 | Viewed by 3559

Abstract

Bacterial biofilm causes severe antibiotic resistance. An extracellular polymeric substance (EPS) is the main component in the bacterial biofilm. Alginate is a key EPS component in the biofilm of Pseudomonas aeruginosa and responsible for surface adhesion and stabilization of biofilm. Alginate lyase has emerged as an efficient therapeutic strategy targeting to degrade the alginate in the biofilm of P. aeruginosa. However, the application of this enzyme is limited by its poor stability. In this study, chitosan nanoparticles (CS-NPs) were synthesized using low molecular weight chitosan and alginate lyase Aly08 was immobilized on low molecular weight chitosan nanoparticles (AL-LMW-CS-NPs). As a result, the immobilization significantly enhanced the thermal stability and reusability of Aly08. In addition, compared with free Aly08, the immobilized AL-LMW-CS-NPs exhibited higher efficiency in inhibiting biofilm formation and interrupting the established mature biofilm of P. aeruginosa, which could reduce its biomass and thickness confirmed by confocal microscopy. Moreover, the biofilm disruption greatly increased the antibiotic sensitivity of P. aeruginosa. This research will contribute to the further development of alginate lyase as an anti-biofilm agent. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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10 pages, 4348 KiB

Open AccessArticle

The Acute Effects of Oral Administration of Phytic Acid-Chitosan-Magnetic Iron Oxide Nanoparticles in Mice

by Norain Mohd Tamsir, Norhaizan Mohd Esa, Nurul Husna Shafie, Mohd Zobir Hussein, Hazilawati Hamzah and Maizaton Atmadini Abdullah

Int. J. Mol. Sci. 2019, 20(17), 4114; https://doi.org/10.3390/ijms20174114 - 23 Aug 2019

Cited by 9 | Viewed by 3139

Abstract

A nanocomposite, phytic acid-chitosan-magnetic iron oxide nanoparticles (IP₆-CS-MNPs) has been used to treat colon cancer in vitro, previously. However, its potential toxicity in vivo has yet to be elucidated. Hence, the present study aimed to evaluate the acute effects of oral administration of IP₆-CS-MNPs in mice. In this study, 1000 and 2000 mg/kg body weight (b.w) of IP₆-CS-MNPs were orally administered to two different groups of BALB/c mice, once. Additionally, the mice in the control group were given only deionized water. After 14 days of post-IP₆-CS-MNPs administration, in a similar way to the untreated mice, the treated mice showed no sign of mortality and abnormalities. However, the serum urea level of mice receiving 2000 mg/kg b.w of IP₆-CS-MNPs was significantly higher than the control group (p < 0.05). The mice that received 1000 mg/kg IP₆-CS-MNPs showed a significantly higher level of serum alkaline phosphatase (ALP) compared to the control group. However, there were no significant histopathological changes seen in the liver and kidneys of treated mice compared to the untreated group. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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12 pages, 4696 KiB

Open AccessArticle

Sponges of Carboxymethyl Chitosan Grafted with Collagen Peptides for Wound Healing

by Yu Cheng, Zhang Hu, Yuntao Zhao, Zuhao Zou, Sitong Lu, Bijun Zhang and Sidong Li

Int. J. Mol. Sci. 2019, 20(16), 3890; https://doi.org/10.3390/ijms20163890 - 09 Aug 2019

Cited by 41 | Viewed by 6872

Abstract

Burns are physically debilitating and potentially fatal injuries. Two marine biomaterials, carboxymethyl chitosan (CMC) and collagen peptides (COP), have emerged as promising burn dressings. In this paper, sponges of carboxymethyl chitosan grafted with collagen peptide (CMC–COP) were prepared by covalent coupling and freeze drying. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were then used to characterize the prepared sponges. To evaluate the wound healing activity of the CMC–COP sponges, in vitro tests including cell viability scratch wound healing and scald wound healing experiments were performed in rabbits. Appearance studies revealed the porous nature of sponges and FTIR spectroscopy demonstrated the successful incorporation of COP into CMC. The in vitro scratch assay showed that treatment with CMC–COP sponges (at 100 μg/mL) had significant effects on scratch closure. For burn wounds treated with CMC–COP, regeneration of the epidermis and collagen fiber deposition was observed on day 7, with complete healing of the epidermis and wound on days 14 and 21, respectively. Based on the pathological examination by hematoxylin and eosinstaining, the CMC–COP group demonstrated pronounced wound healing efficiencies. These results confirmed that the CMC–COP treatment enhanced cell migration and promoted skin regeneration, thereby highlighting the potential application of these sponges in burn care. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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16 pages, 4708 KiB

Open AccessArticle

Design and Characterization of Chitosan Nanoformulations for the Delivery of Antifungal Agents

by Natalia L. Calvo, Sruthi Sreekumar, Laura A. Svetaz, María C. Lamas, Bruno M. Moerschbacher and Darío Leonardi

Int. J. Mol. Sci. 2019, 20(15), 3686; https://doi.org/10.3390/ijms20153686 - 27 Jul 2019

Cited by 24 | Viewed by 3461

Abstract

Among different Candida species triggering vaginal candidiasis, Candida albicans is the most predominant yeast. It is commonly treated using azole drugs such as Tioconazole (TIO) and Econazole (ECO). However, their low water solubility may affect their therapeutic efficiency. Therefore, the aim of this research was to produce a novel chitosan nanocapsule based delivery system comprising of TIO or ECO and to study their suitability in vaginal application. These systems were characterized by their physicochemical properties, encapsulation efficiency, in vitro release, storage stability, cytotoxicity, and in vitro biological activity. Both nanocapsules loaded with TIO (average hydrodynamic size of 146.8 ± 0.8 nm, zeta potential of +24.7 ± 1.1 mV) or ECO (average hydrodynamic size of 127.1 ± 1.5 nm, zeta potential of +33.0 ± 1.0 mV) showed excellent association efficiency (99% for TIO and 87% for ECO). The analysis of size, polydispersity index, and zeta potential of the systems at 4, 25, and 37 °C (over a period of two months) showed the stability of the systems. Finally, the developed nanosystems presented fungicidal activity against C. albicans at non-toxic concentrations (studied on model human skin cells). The results obtained from this study are the first step in the development of a pharmaceutical dosage form suitable for the treatment of vaginal candidiasis. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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10 pages, 2001 KiB

Open AccessArticle

Selective Anticancer Therapy Using Pro-Oxidant Drug-Loaded Chitosan–Fucoidan Nanoparticles

by Dae Gun Choi, Jayachandran Venkatesan and Min Suk Shim

Int. J. Mol. Sci. 2019, 20(13), 3220; https://doi.org/10.3390/ijms20133220 - 30 Jun 2019

Cited by 55 | Viewed by 4701

Abstract

Pro-oxidant therapy exploiting pro-oxidant drugs that can trigger cytotoxic oxidative stress in cancer cells has emerged as an innovative strategy for cancer-specific therapy. Piperlongumine (PL) has gained great interest as a novel pro-oxidant agent, because it has an ability to trigger cancer-specific apoptosis through the increase of oxidative stress in cancer cells. However, the use of PL is limited in the clinic because of its hydrophobic nature. In this study, chitosan- and fucoidan-based nanoparticles were prepared for the effective intracellular delivery of PL into cancer cells. Chitosan and fucoidan formed nanoparticles by ionic gelation. The chitosan- and fucoidan-based nanoparticles (CS–F NPs) effectively encapsulated PL, and increased its water solubility and bioavailability. CS–F NPs showed very low cytotoxicity in human prostate cancer cells, demonstrating its high potential for in vivo applications. The PL-loaded chitosan–fucoidan nanoparticles (PL-CS–F NPs) efficiently killed human prostate cancer cells via PL-induced intracellular reactive oxygen species (ROS) generation. This study demonstrates that CS–F NPs are promising natural polymer-based drug carriers for safe and effective PL delivery. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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14 pages, 5355 KiB

Open AccessArticle

Biocompatible and Antimicrobial Electrospun Membranes Based on Nanocomposites of Chitosan/Poly (Vinyl Alcohol)/Graphene Oxide

by Julián Andrés Tamayo Marín, Sebastián Ruiz Londoño, Johannes Delgado, Diana Paola Navia Porras, Mayra Eliana Valencia Zapata, José Herminsul Mina Hernandez, Carlos Humberto Valencia and Carlos David Grande Tovar

Int. J. Mol. Sci. 2019, 20(12), 2987; https://doi.org/10.3390/ijms20122987 - 19 Jun 2019

Cited by 30 | Viewed by 3680

Abstract

Tissue engineering is gaining attention rapidly to replace and repair defective tissues in the human body after illnesses and accidents in different organs. Electrospun nanofiber scaffolds have emerged as a potential alternative for cell regeneration and organ replacement. In this paper, porous membranes, based on nanofibrous chitosan (CS), polyvinyl alcohol (PVA), and graphene oxide (GO), were obtained via electrospinning methodology. Three different formulations were obtained varying GO content, being characterized by Fourier Transform Infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). In vitro tests were carried out, consisting of hydrolytic degradation inside simulated biological fluid (SBF), and in vivo tests were carried out, where the material was implanted in Wistar rats’ subcutaneous tissue to determine its biocompatibility. The antibacterial activity was tested against Gram-positive bacteria Bacillus cereus and Staphylococcus aureus, and against Gram-negative Salmonella enterica and Escherichia coli, by contact of the electrospun nanofiber scaffolds above inoculum bacterial in Müeller Hinton agar with good inhibition only for scaffolds with the higher GO content (1.0%). The results confirmed good biocompatibility of the nanofibrous scaffolds after in vivo tests in Wistar rats, which evidences its high potential in applications of tissue regeneration. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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18 pages, 5063 KiB

Open AccessArticle

Novel Bioactive and Antibacterial Acrylic Bone Cement Nanocomposites Modified with Graphene Oxide and Chitosan

by Mayra Eliana Valencia Zapata, José Herminsul Mina Hernandez, Carlos David Grande Tovar, Carlos Humberto Valencia Llano, José Alfredo Diaz Escobar, Blanca Vázquez-Lasa, Julio San Román and Luis Rojo

Int. J. Mol. Sci. 2019, 20(12), 2938; https://doi.org/10.3390/ijms20122938 - 15 Jun 2019

Cited by 43 | Viewed by 4833

Abstract

Acrylic bone cements (ABCs) have played a key role in orthopedic surgery mainly in arthroplasties, but their use is increasingly extending to other applications, such as remodeling of cancerous bones, cranioplasties, and vertebroplasties. However, these materials present some limitations related to their inert behavior and the risk of infection after implantation, which leads to a lack of attachment and makes necessary new surgical interventions. In this research, the physicochemical, thermal, mechanical, and biological properties of ABCs modified with chitosan (CS) and graphene oxide (GO) were studied. Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (¹H-NMR) scanning electron microscopy (SEM), Raman mapping, thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), compression resistance, mechanical dynamic analysis (DMA), hydrolytic degradation, cell viability, alkaline phosphatase (ALP) activity with human osteoblasts (HOb), and antibacterial activity against Gram-negative bacteria Escherichia coli were used to characterize the ABCs. The results revealed good dispersion of GO nanosheets in the ABCs. GO provided an increase in antibacterial activity, roughness, and flexural behavior, while CS generated porosity, increased the rate of degradation, and decreased compression properties. All ABCs were not cytotoxic and support good cell viability of HOb. The novel formulation of ABCs containing GO and CS simultaneously, increased the thermal stability, flexural modulus, antibacterial behavior, and osteogenic activity, which gives it a high potential for its uses in orthopedic applications. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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14 pages, 2693 KiB

Open AccessArticle

Cherry Extract from Prunus avium L. to Improve the Resistance of Endothelial Cells to Oxidative Stress: Mucoadhesive Chitosan vs. Poly(lactic-co-glycolic acid) Nanoparticles

by Denise Beconcini, Angela Fabiano, Rossella Di Stefano, Maria Helena Macedo, Francesca Felice, Ylenia Zambito and Bruno Sarmento

Int. J. Mol. Sci. 2019, 20(7), 1759; https://doi.org/10.3390/ijms20071759 - 10 Apr 2019

Cited by 16 | Viewed by 3852

Abstract

Polyphenolic compounds contained in cherry extract (CE) are well known for their antioxidant and anti-inflammatory properties. Unfortunately, most of these natural compounds have low oral bioavailability, reducing their widespread use. Here, different concentrations of polyphenol-rich CE from Tuscany (Italy), encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), were compared with those encapsulated in two NP types, different from each other in terms of mucoadhesivity, obtained with chitosan derivatives (Ch-der), regarding CE gastrointestinal (GI) permeability and protective effect on oxidative stress. Different NP systems were physico-chemically characterized, and the antioxidant GI permeability was evaluated in a triple-cell co-culture model (Caco-2/HT29-MTX/Raji B), resembling the intestine. PLGA NPs efficiently entrapped CE (up to 840 µg gallic acid equivalent (GAE)/mL) without altering size (210 nm), polydispersity index (0.05), or zeta potential (−10.7 mV). Such NPs promoted permeation of encapsulated CE at a CE polyphenolic concentration of at least 2 µg GAE/mL. More mucoadhesive NPs from Ch-der, coded quaternary ammonium S-protected thiolated chitosan (QA-Ch-S-pro) NP, promoted CE GI permeation of 0.5 µg GAE/mL. At higher concentrations of Ch-der polymers, the resulting NPs containing CE were toxic toward Caco-2 and HT29-MTX cells. CE protected human umbilical vein endothelial cells (HUVECs) from oxidative stress and maintained its activity when entrapped in PLGA NPs. CE encapsulated in QA-Ch-S-pro NP protected HUVECs from oxidative stress, even more effectively than non-encapsulated CE. Furthermore, mucoadhesive NPs from Ch-der were more effective antioxidant protectors than PLGA NPs, but less cytotoxic PLGA NPs could be more useful when comparatively high therapeutic antioxidant doses are needed. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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9 pages, 5027 KiB

Open AccessArticle

Evaluation of the Biocompatibility of CS-Graphene Oxide Compounds In Vivo

by Diego López Tenorio, Carlos H. Valencia, Cesar Valencia, Fabio Zuluaga, Mayra E. Valencia, José H. Mina and Carlos David Grande Tovar

Int. J. Mol. Sci. 2019, 20(7), 1572; https://doi.org/10.3390/ijms20071572 - 29 Mar 2019

Cited by 17 | Viewed by 3910

Abstract

In the last few years, graphene oxide (GO) has gained considerable importance in scaffold preparation for tissue engineering due to the presence of functional groups that allow the interaction between the extracellular matrix and the components of the cellular membrane. The interaction between GO and chitosan (CS) can not only improve the biomechanical properties of the scaffold but also generate a synergistic effect, facilitating tissue recovery. In vivo studies on GO are scarce; therefore, biocompatibility tests on CS-GO scaffolds and bone regeneration experiments on critical size defects were carried out on Wistar rats. Scaffolds made of CS, CS-GO 0.5%, and CS-GO 1% were prepared and implanted on Wistar rats cranial bones for three months. Scaffold samples were analyzed through histochemistry and scanning electron microscopy. The analysis performed showed reabsorption of the material by phagocytic activity and new bone formation. The CS-GO 0.5% formulation gave the best performance in bone regeneration, with excellent biocompatibility. These results show the potential of this compound for tissue regeneration opening and medical applications. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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Review

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24 pages, 2045 KiB

Open AccessReview

Synthesis, Bioapplications, and Toxicity Evaluation of Chitosan-Based Nanoparticles

by Balsam R. Rizeq, Nadin N. Younes, Kashif Rasool and Gheyath K. Nasrallah

Int. J. Mol. Sci. 2019, 20(22), 5776; https://doi.org/10.3390/ijms20225776 - 16 Nov 2019

Cited by 160 | Viewed by 10296

Abstract

The development of advanced nanomaterials and technologies is essential in biomedical engineering to improve the quality of life. Chitosan-based nanomaterials are on the forefront and attract wide interest due to their versatile physicochemical characteristics such as biodegradability, biocompatibility, and non-toxicity, which play a promising role in biological applications. Chitosan and its derivatives are employed in several applications including pharmaceuticals and biomedical engineering. This article presents a comprehensive overview of recent advances in chitosan derivatives and nanoparticle synthesis, as well as emerging applications in medicine, tissue engineering, drug delivery, gene therapy, and cancer therapy. In addition to the applications, we critically review the main concerns and mitigation strategies related to chitosan bactericidal properties, toxicity/safety using tissue cultures and animal models, and also their potential environmental impact. At the end of this review, we also provide some of future directions and conclusions that are important for expanding the field of biomedical applications of the chitosan nanoparticles. Full article

(This article belongs to the Special Issue Chitosan-Based Nanoparticles)

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