Alginate-Based Biomaterials and Drug Delivery

A special issue of Marine Drugs (ISSN 1660-3397). This special issue belongs to the section "Biomaterials of Marine Origin".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 28934

Special Issue Editors

Department of Chemistry and Industrial Chemistry, University of Genoa, Genoa, Italy
Interests: sodium alginate; alginate–polymethacrylate hybrid hydrogels; functional polymeric materials; biomaterials; polymeric nanostructures; study of the physical properties; rheology and mechanical properties of polymers; surface modification and surface properties characterization of polymeric materials
Special Issues, Collections and Topics in MDPI journals
Department of Chemistry and Industrial Chemistry, University of Genoa, Via Dodecaneso 31, 16146 Genoa, Italy
Interests: biopolymers; biomedical applications; hydrogels; electrospinning; rheology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In recent years, alginate polysaccharide has assumed a major role as a promising and innovative biomaterial, and it has been indeed broadly explored in biomedical science and engineering owing to its biocompatibility, biodegradability, low immunogenicity, and gelling capabilities. Indeed, despite the most common use of this polysaccharide being related to food products, alginate-based materials show great potentialities for several biomedical purposes that are able to mimic many functions of the extracellular matrices of body tissues. For instance, recent advances in wound healing, drug delivery, and tissue engineering have been achieved by using alginate-based hydrogels, fibers, capsules, and particles.

This Special Issue is devoted to both original research articles and reviews covering any aspect, from extraction to application, of alginate-based materials for biomedical and/or pharmaceutical purposes. As Guest Editors, we particularly encourage Authors to submit their latest findings showing significant advances in this field.

Prof. Dr. Maila Castellano
Dr. Andrea Dodero
Guest Editors

Manuscript Submission Information

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Keywords

  • alginate
  • hydrogels
  • scaffolds
  • biomedical applications
  • drug delivery

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Published Papers (10 papers)

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Research

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14 pages, 2350 KiB  
Article
Alginate Microsphere Encapsulation of Drug-Loaded Nanoparticles: A Novel Strategy for Intraperitoneal Drug Delivery
by Karianne Giller Fleten, Astrid Hyldbakk, Caroline Einen, Sopisa Benjakul, Berit Løkensgard Strand, Catharina de Lange Davies, Ýrr Mørch and Kjersti Flatmark
Mar. Drugs 2022, 20(12), 744; https://doi.org/10.3390/md20120744 - 26 Nov 2022
Cited by 3 | Viewed by 2184
Abstract
Alginate hydrogels have been broadly investigated for use in medical applications due to their biocompatibility and the possibility to encapsulate cells, proteins, and drugs. In the treatment of peritoneal metastasis, rapid drug clearance from the peritoneal cavity is a major challenge. Aiming to [...] Read more.
Alginate hydrogels have been broadly investigated for use in medical applications due to their biocompatibility and the possibility to encapsulate cells, proteins, and drugs. In the treatment of peritoneal metastasis, rapid drug clearance from the peritoneal cavity is a major challenge. Aiming to delay drug absorption and reduce toxic side effects, cabazitaxel (CAB)-loaded poly(alkyl cyanoacrylate) (PACA) nanoparticles were encapsulated in alginate microspheres. The PACAlg alginate microspheres were synthesized by electrostatic droplet generation and the physicochemical properties, stability, drug release kinetics, and mesothelial cytotoxicity were analyzed before biodistribution and therapeutic efficacy were studied in mice. The 450 µm microspheres were stable at in vivo conditions for at least 21 days after intraperitoneal implantation in mice, and distributed evenly throughout the peritoneal cavity without aggregation or adhesion. The nanoparticles were stably retained in the alginate microspheres, and nanoparticle toxicity to mesothelial cells was reduced, while the therapeutic efficacy of free CAB was maintained or improved in vivo. Altogether, this work presents the alginate encapsulation of drug-loaded nanoparticles as a promising novel strategy for the treatment of peritoneal metastasis that can improve the therapeutic ratio between toxicity and therapeutic efficacy. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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19 pages, 6526 KiB  
Article
Effects of Formulation on the Palatability and Efficacy of In-Feed Praziquantel Medications for Marine Finfish Aquaculture
by Edith K. Y. Tang, Gavin J. Partridge, Lindsey D. Woolley, Luke Pilmer and Lee Yong Lim
Mar. Drugs 2022, 20(5), 323; https://doi.org/10.3390/md20050323 - 13 May 2022
Cited by 1 | Viewed by 1994
Abstract
Praziquantel (PZQ) provides an effective treatment against monogenean parasitic infestations in finfish. However, its use as an in-feed treatment is challenging due to palatability issues. In this study, five formulations of PZQ beads (1–4 mm) were developed using marine-based polymers, with allicin added [...] Read more.
Praziquantel (PZQ) provides an effective treatment against monogenean parasitic infestations in finfish. However, its use as an in-feed treatment is challenging due to palatability issues. In this study, five formulations of PZQ beads (1–4 mm) were developed using marine-based polymers, with allicin added as a flavouring agent. All formulations attained PZQ loading rates ≥74% w/w, and the beads were successfully incorporated into fish feed pellets at an active dietary inclusion level of 10 g/kg. When tested for palatability and digestibility in small yellowtail kingfish, the PZQ-loaded beads produced with alginate-chitosan, alginate-Cremophor® RH40, and agar as carriers resulted in high consumption rates of 99–100% with no digesta or evidence of beads in the gastrointestinal tract (GIT) of fish fed with diets containing either formulation. Two formulations produced using chitosan-based carriers resulted in lower consumption rates of 68–75%, with undigested and partly digested beads found in the fish GIT 3 h post feeding. The PZQ-loaded alginate-chitosan and agar beads also showed good palatability in large (≥2 kg) yellowtail kingfish infected with gill parasites and were efficacious in removing the parasites from the fish, achieving >90% reduction in mean abundance relative to control fish (p < 0.001). The two effective formulations were stable upon storage at ambient temperature for up to 18 months, showing residual drug content >90% compared with baseline levels. Overall, the palatability, efficacy and stability data collected from this study suggest that these two PZQ particulate formulations have potential applications as in-feed anti-parasitic medications for the yellowtail kingfish farming industry. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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15 pages, 1724 KiB  
Article
Chitosan/Alginate Nanoparticles for the Enhanced Oral Antithrombotic Activity of Clam Heparinoid from the Clam Coelomactra antiquata
by Guan-Lan Chen, Hong-Ying Cai, Jian-Ping Chen, Rui Li, Sai-Yi Zhong, Xue-Jing Jia, Xiao-Fei Liu and Bing-Bing Song
Mar. Drugs 2022, 20(2), 136; https://doi.org/10.3390/md20020136 - 12 Feb 2022
Cited by 7 | Viewed by 2610
Abstract
Chitosan/alginate nanoparticles (DG1-NPs and DG1/Cur-NPs) aiming to enhance the oral antithrombotic activity of clam heparinoid DG1 were prepared by ionotropic pre-gelation. The influence of parameters, such as the concentration of sodium alginate (SA), chitosan (CTS), CaCl2, clam heparinoid DG1, and curcumin [...] Read more.
Chitosan/alginate nanoparticles (DG1-NPs and DG1/Cur-NPs) aiming to enhance the oral antithrombotic activity of clam heparinoid DG1 were prepared by ionotropic pre-gelation. The influence of parameters, such as the concentration of sodium alginate (SA), chitosan (CTS), CaCl2, clam heparinoid DG1, and curcumin (Cur), on the characteristics of the nanoparticles, were investigated. Results indicate that chitosan and alginate can be used as polymer matrices to encapsulate DG1, and nanoparticle characteristics depend on the preparation parameters. Nano-particles should be prepared using 0.6 mg/mL SA, 0.33 mg/mL CaCl2, 0.6 mg/mL CTS, 7.2 mg/mL DG1, and 0.24 mg/mL Cur under vigorous stirring to produce DG1-NPS and DG1/Cur-NPS with small size, high encapsulation efficiency, high loading capacity, and negative zeta potential from approximately −20 to 30 mV. Data from scanning electron microscopy, Fourier-transform infrared spectrometry, and differential scanning calorimetry analyses showed no chemical reaction between DG1, Cur, and the polymers; only physical mixing. Moreover, the drug was loaded in the amorphous phase within the nanoparticle matrix. In the acute pulmonary embolism murine model, DG1-NPs enhanced the oral antithrombotic activity of DG1, but DG1/Cur-NPs did not exhibit higher antithrombotic activity than DG1-NPs. Therefore, the chitosan/alginate nanoparticles enhanced the oral antithrombotic activity of DG1, but curcumin did not further enhance this effect. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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16 pages, 7760 KiB  
Article
Cloning and Characterization of a Novel Alginate Lyase from Paenibacillus sp. LJ-23
by Mingpeng Wang, Lei Chen, Zhengyu Lou, Xueting Yuan, Guiping Pan, Xiaoyan Ren and Pengyu Wang
Mar. Drugs 2022, 20(1), 66; https://doi.org/10.3390/md20010066 - 12 Jan 2022
Cited by 6 | Viewed by 1946
Abstract
As a low molecular weight alginate, alginate oligosaccharides (AOS) exhibit improved water solubility, better bioavailability, and comprehensive health benefits. In addition, their biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and gelling capability make them an excellent biomaterial with a dual curative effect when applied in a [...] Read more.
As a low molecular weight alginate, alginate oligosaccharides (AOS) exhibit improved water solubility, better bioavailability, and comprehensive health benefits. In addition, their biocompatibility, biodegradability, non-toxicity, non-immunogenicity, and gelling capability make them an excellent biomaterial with a dual curative effect when applied in a drug delivery system. In this paper, a novel alginate lyase, Algpt, was cloned and characterized from a marine bacterium, Paenibacillus sp. LJ-23. The purified enzyme was composed of 387 amino acid residues, and had a molecular weight of 42.8 kDa. The optimal pH of Algpt was 7.0 and the optimal temperature was 45 °C. The analysis of the conserved domain and the prediction of the three-dimensional structure indicated that Algpt was a novel alginate lyase. The dominant degradation products of Algpt on alginate were AOS dimer to octamer, depending on the incubation time, which demonstrated that Algpt degraded alginate in an endolytic manner. In addition, Algpt was a salt-independent and thermo-tolerant alginate lyase. Its high stability and wide adaptability endow Algpt with great application potential for the efficient preparation of AOS with different sizes and AOS-based products. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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9 pages, 1326 KiB  
Article
A Promising Potential of Brown Algae Sargassum polycystum as Irreversible Hydrocolloid Impression Material
by Nurlindah Hamrun, Bahruddin Talib, Muhammad Ruslin, Hasminar Pangeran, Mochammad Hatta, Erni Marlina, Andi Sitti Hajrah Yusuf, Takashi Saito and Keng-Liang Ou
Mar. Drugs 2022, 20(1), 55; https://doi.org/10.3390/md20010055 - 06 Jan 2022
Cited by 3 | Viewed by 2233
Abstract
This study aimed to investigate the potential use of brown algae Sargassum polycystum as irreversible hydrocolloid (alginate) impression material. Potassium alginate extracted from Sargassum polycystum was prepared in three different compositions (14%, 15%, and 16%) and mixed with other standard components to form [...] Read more.
This study aimed to investigate the potential use of brown algae Sargassum polycystum as irreversible hydrocolloid (alginate) impression material. Potassium alginate extracted from Sargassum polycystum was prepared in three different compositions (14%, 15%, and 16%) and mixed with other standard components to form an alginate impression material. Prior to that, the purity of potassium alginate was quantified with Fourier Transform Infrared Spectroscopy (FTIR) analysis. As a control material, the alginate impression material from a commercially available product was used. All alginate impression materials were then applied to a die stone model. Dimensional accuracy was measured by calculating the mesiodistal width of incisors in the generated dental cast using a digital caliper 0.01 accuracy (five replications). In addition, to evaluate the dimensional stability, the impression results were poured at four different periods (immediately, 5 min, 10 min, and 15 min). An independent t-test was performed to compare the measurement results with p < 0.05 considered significant. Analytical results confirm that the impression material containing 15% potassium alginate gives the best dimensional accuracy similar to control (p > 0.05). Meanwhile, the optimal dimensional stability was produced in the impression material containing 16% potassium alginate. Our study suggested that brown algae Sargassum polycystum has a promising potential to be used as an alginate impression material in clinical application. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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18 pages, 3601 KiB  
Article
Fabrication and Characterization of Nanocomposite Hydrogel Based on Alginate/Nano-Hydroxyapatite Loaded with Linum usitatissimum Extract as a Bone Tissue Engineering Scaffold
by Mahnaz Mohammadpour, Hadi Samadian, Nader Moradi, Zhila Izadi, Mahdieh Eftekhari, Masoud Hamidi, Amin Shavandi, Anthony Quéro, Emmanuel Petit, Cédric Delattre and Redouan Elboutachfaiti
Mar. Drugs 2022, 20(1), 20; https://doi.org/10.3390/md20010020 - 23 Dec 2021
Cited by 14 | Viewed by 3521
Abstract
In the current paper, we fabricated, characterized, and applied nanocomposite hydrogel based on alginate (Alg) and nano-hydroxyapatite (nHA) loaded with phenolic purified extracts from the aerial part of Linum usitatissimum (LOH) as the bone tissue engineering scaffold. nHA was synthesized based on the [...] Read more.
In the current paper, we fabricated, characterized, and applied nanocomposite hydrogel based on alginate (Alg) and nano-hydroxyapatite (nHA) loaded with phenolic purified extracts from the aerial part of Linum usitatissimum (LOH) as the bone tissue engineering scaffold. nHA was synthesized based on the wet chemical technique/precipitation reaction and incorporated into Alg hydrogel as the filler via physical cross-linking. The characterizations (SEM, DLS, and Zeta potential) revealed that the synthesized nHA possess a plate-like shape with nanometric dimensions. The fabricated nanocomposite has a porous architecture with interconnected pores. The average pore size was in the range of 100–200 µm and the porosity range of 80–90%. The LOH release measurement showed that about 90% of the loaded drug was released within 12 h followed by a sustained release over 48 h. The in vitro assessments showed that the nanocomposite possesses significant antioxidant activity promoting bone regeneration. The hemolysis induction measurement showed that the nanocomposites were hemocompatible with negligible hemolysis induction. The cell viability/proliferation confirmed the biocompatibility of the nanocomposites, which induced proliferative effects in a dose-dependent manner. This study revealed the fabricated nanocomposites are bioactive and osteoactive applicable for bone tissue engineering applications. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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18 pages, 22355 KiB  
Article
Development and Characterization of Calcium-Alginate Beads of Apigenin: In Vitro Antitumor, Antibacterial, and Antioxidant Activities
by Mohammed F. Aldawsari, Mohammed Muqtader Ahmed, Farhat Fatima, Md. Khalid Anwer, Prakash Katakam and Abdullah Khan
Mar. Drugs 2021, 19(8), 467; https://doi.org/10.3390/md19080467 - 20 Aug 2021
Cited by 22 | Viewed by 6522
Abstract
The objective of this work was to develop sustained-release Ca-alginate beads of apigenin using sodium alginate, a natural polysaccharide. Six batches were prepared by applying the ionotropic gelation technique, wherein calcium chloride was used as a crosslinking agent. The beads were evaluated for [...] Read more.
The objective of this work was to develop sustained-release Ca-alginate beads of apigenin using sodium alginate, a natural polysaccharide. Six batches were prepared by applying the ionotropic gelation technique, wherein calcium chloride was used as a crosslinking agent. The beads were evaluated for particle size, drug loading, percentage yield, and in vitro drug release. Particle size was found to decrease, and drug entrapment efficiency was enhanced with an increase in the polymer concentration. The dissolution study showed sustained drug release from the apigenin-loaded alginate beads with an increase in the polymer proportion. Based on the dissolution profiles, BD6 formulation was optimized and characterized for FTIR, DSC, XRD, and SEM, results of which indicated successful development of apigenin-loaded Ca alginate beads. MTT assay demonstrated a potential anticancer effect against the breast cancer MCF-7 cell lines. The antimicrobial activity exhibited effective inhibition in the bacterial and fungal growth rate. The DPPH measurement revealed that the formulation had substantial antioxidant activity, with EC50 value slightly lowered compared to pure apigenin. A stability study demonstrated that the BD6 was stable with similar (f2) drug release profiles in harsh condition. In conclusion, alginate-based beads could be used for sustaining the drug release of poorly water-soluble apigenin while also improving in vitro antitumor, antimicrobial, and antioxidant activity. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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Review

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33 pages, 2032 KiB  
Review
Alginates Combined with Natural Polymers as Valuable Drug Delivery Platforms
by Katarzyna Kruk and Katarzyna Winnicka
Mar. Drugs 2023, 21(1), 11; https://doi.org/10.3390/md21010011 - 23 Dec 2022
Cited by 8 | Viewed by 2235
Abstract
Alginates (ALG) have been used in biomedical and pharmaceutical technologies for decades. ALG are natural polymers occurring in brown algae and feature multiple advantages, including biocompatibility, low toxicity and mucoadhesiveness. Moreover, ALG demonstrate biological activities per se, including anti-hyperlipidemic, antimicrobial, anti-reflux, immunomodulatory or [...] Read more.
Alginates (ALG) have been used in biomedical and pharmaceutical technologies for decades. ALG are natural polymers occurring in brown algae and feature multiple advantages, including biocompatibility, low toxicity and mucoadhesiveness. Moreover, ALG demonstrate biological activities per se, including anti-hyperlipidemic, antimicrobial, anti-reflux, immunomodulatory or anti-inflammatory activities. ALG are characterized by gelling ability, one of the most frequently utilized properties in the drug form design. ALG have numerous applications in pharmaceutical technology that include micro- and nanoparticles, tablets, mucoadhesive dosage forms, wound dressings and films. However, there are some shortcomings, which impede the development of modified-release dosage forms or formulations with adequate mechanical strength based on pure ALG. Other natural polymers combined with ALG create great potential as drug carriers, improving limitations of ALG matrices. Therefore, in this paper, ALG blends with pectins, chitosan, gelatin, and carrageenans were critically reviewed. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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14 pages, 1647 KiB  
Review
Alginate-Based Micro- and Nanosystems for Targeted Cancer Therapy
by Siavash Iravani and Rajender S. Varma
Mar. Drugs 2022, 20(10), 598; https://doi.org/10.3390/md20100598 - 23 Sep 2022
Cited by 14 | Viewed by 2397
Abstract
Alginates have been widely explored due to their salient advantages of hydrophilicity, biocompatibility, mucoadhesive features, bioavailability, environmentally-benign properties, and cost-effectiveness. They are applied for designing micro- and nanosystems for controlled and targeted drug delivery and cancer therapy as alginate biopolymers find usage in [...] Read more.
Alginates have been widely explored due to their salient advantages of hydrophilicity, biocompatibility, mucoadhesive features, bioavailability, environmentally-benign properties, and cost-effectiveness. They are applied for designing micro- and nanosystems for controlled and targeted drug delivery and cancer therapy as alginate biopolymers find usage in encapsulating anticancer drugs to improve their bioavailability, sustained release, pharmacokinetics, and bio-clearance. Notably, these nanomaterials can be applied for photothermal, photodynamic, and chemodynamic therapy of cancers/tumors. Future explorations ought to be conducted to find novel alginate-based (nano)systems for targeted cancer therapy using advanced drug delivery techniques with benefits of non-invasiveness, patient compliance, and convenience of drug administration. Thus, some critical parameters such as mucosal permeability, stability in the gastrointestinal tract environment, and drug solubility ought to be considered. In addition, the comprehensive clinical translational studies along with the optimization of synthesis techniques still need to be addressed. Herein, we present an overview of the current state of knowledge and recent developments pertaining to the applications of alginate-based micro- and nanosystems for targeted cancer therapy based on controlled drug delivery, photothermal therapy, and chemodynamic/photodynamic therapy approaches, focusing on important challenges and future directions. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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12 pages, 690 KiB  
Review
An Insight into the Role of Marine Biopolymer Alginate in Endodontics: A Review
by Galvin Sim Siang Lin, Chia Yee Cher, Yong Hong Goh, Daryl Zhun Kit Chan, Mohmed Isaqali Karobari, Josephine Chang Hui Lai and Tahir Yusuf Noorani
Mar. Drugs 2022, 20(8), 539; https://doi.org/10.3390/md20080539 - 22 Aug 2022
Cited by 5 | Viewed by 2003
Abstract
Alginate is a natural marine biopolymer that has been widely used in biomedical applications, but research on its use as an endodontic material is still sparse in the literature. This pioneer review aims to summarize the emerging roles of alginate and to outline [...] Read more.
Alginate is a natural marine biopolymer that has been widely used in biomedical applications, but research on its use as an endodontic material is still sparse in the literature. This pioneer review aims to summarize the emerging roles of alginate and to outline its prospective applications as a core biomaterial in endodontics. Ten electronic databases and five textbooks were used to perform a search of English-language literature on the use of alginate in endodontics published between January 1980 and June 2022. The risk of bias (RoB) of each included study was assessed using the Office of Health Assessment and Translation (OHAT) tool. Subsequently, studies were categorized into three tiers to represent the overall risk. Qualitative analysis was performed, and the articles were sorted into different thematic categories. An initial search yielded a total of 1491 articles, but only 13 articles were chosen. For most domains, all the studies were rated with ‘probably low’ or ‘definitely low’ RoB, except for domains 2 and 6. All included studies fall in the Tier 1 category and were either in vitro, in vivo, or ex vivo. Four thematic categories were identified: endodontic regeneration, intracanal medicament, filing material, and chelating agent. Based on the available evidence, alginate has emerged as a cell carrier and scaffold in regenerative endodontics, a microcapsule delivery system for intracanal medicaments, a chelating agent reinforcing material, and a root canal sealer. More well-designed experiments and clinical trials are needed to warrant the promising advent of this hydrogel-based biomaterial. Full article
(This article belongs to the Special Issue Alginate-Based Biomaterials and Drug Delivery)
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