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Carbohydrate-Based Carriers for Drug Delivery

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (31 August 2024) | Viewed by 21835

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Dr. Ioana Mirela Vasincu

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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 Universitaty Street, 700115 Iași, Romania
Interests: drug delivery; anti-inflammatory and analgesic effects; cyclodextrin inclusion complexes; ibuprofen derivatives; chemical synthesis; ionic liquids; polymers
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Dr. Florentina Lupascu

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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 Universitaty Street, 700115 Iași, Romania
Interests: organic synthesis; chitosan microparticles and nanoparticles; antioxidant activity; diabetes mellitus type 2; drug delivery systems; drug loading; release profile
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Dr. Maria Apotrosoaei

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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 Universitaty Street, 700115 Iași, Romania
Interests: anti-inflammatory potential; organic synthesis; nanogels; liposomes; nanocarriers; drug delivery systems
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Prof. Dr. Lenuta Profire

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Department of Pharmaceutical Chemistry, Faculty of Pharmacy, “Grigore T. Popa” University of Medicine and Pharmacy of Iași, 16 Universitaty Street, 700115 Iași, Romania
Interests: organic synthesis; drug delivery systems (liposomes, niosomes, chitosan nanoparticles, nanofiber, nanofibers, films, sponges); molecular docking; structure-based drug design strategies; antioxidant activity; anti-inflammatory activity; diabetes mellitus type 2
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Special Issue Information

Dear Colleagues,

Carbohydrates, or saccharides, are among the most common molecules found in nature and have biological and structural features that allow for their use in drug delivery systems as carriers. The main classes of these molecules include monosaccharides, oligosaccharides and polisaccharides, which have shown great potential for overcoming the limitations of drugs and navigating biological barriers to achieve targeted delivery. Chitosan, cyclodextrin, alginate, gellan, xanthan gum, cellulose, dextran, pullulan, etc., are some of the most well-known carbohydrate carriers in drug delivery. By protecting the structural integrity of the drug and proving hydrophilic properties, these carriers can modulate undesirable biological properties in drugs as well as their solubility and release profile.

Carbohydrates can improve drug delivery due to their ability to selectively bind to protein receptors, thus increasing drug targeting. They also have the advantages of nontoxicity, biodegradability, good biocompatibility and increased encapsulation stability.

In recent years, carbohydrate-based drug delivery systems have been developed and improved, with their use being of great interest to researchers for the treatment of inflammation, cancer, infections, chronic wounds, diabetes mellitus and other diseases.

This Special Issue will focus on current advances in carbohydrate-based carriers and their applications in drug delivery.

Dr. Ioana Mirela Vasincu
Dr. Florentina Lupascu
Dr. Maria Apotrosoaei
Prof. Dr. Lenuta Profire
Guest Editors

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Keywords

nanomaterials
drug delivery
release profile
polisaccharides
oligosaccharides
inclusion complexes
targeted therapy

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Published Papers (9 papers)

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Research

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13 pages, 3238 KiB

Open AccessEditor’s ChoiceArticle

Derivatization of Hyaluronan to Target Neuroblastoma and Neuroglioma Expressing CD44

by Giau Van Vo, Kummara Madhusudana Rao, Ildoo Chung, Chang-Sik Ha, Seong Soo A. An and Yang H. Yun

Pharmaceutics 2024, 16(6), 836; https://doi.org/10.3390/pharmaceutics16060836 - 20 Jun 2024

Cited by 1 | Viewed by 1272

Abstract

Therapeutics for actively targeting over-expressed receptors are of great interest because the majority of diseased tissues originate from normal cells and do not possess a unique receptor from which they can be differentiated. One such receptor is CD44, which has been shown to be highly overexpressed in many breast cancers and other types of cancer cells. While CD44 has been documented to express low levels in normal adult neurons, astrocytes, and microglia, this receptor may be overexpressed by neuroblastoma and neuroglioma. If differential expression exists between normal and cancerous cells, hyaluronan (HA) could be a useful carrier that targets carcinomas. Thus, HA was conjugated with resveratrol (HA-R), and its efficacy was tested on cortical–neuroblastoma hybrid, neuroblastoma, and neuroglioma cells. Confocal and flow cytometry showed these cells express CD44 and are able to bind and uptake HA-R. The toxicity of HA-R correlated well with CD44 expression in this study. Therefore, conjugating resveratrol and other chemotherapeutics to HA could minimize the side effects for normal cells within the brain and nervous system and could be a viable strategy for developing targeted therapies. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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20 pages, 3786 KiB

Open AccessArticle

The Influence of the Intergranular Superdisintegrant Performance on New Drotaverine Orodispersible Tablet Formulations

by Robert-Alexandru Vlad, Cezara Pintea, Diana-Andreea Chirteș, Paula Antonoaea, Emöke Margit Rédai, Nicoleta Todoran, Magdalena Bîrsan and Adriana Ciurba

Pharmaceutics 2023, 15(8), 2147; https://doi.org/10.3390/pharmaceutics15082147 - 16 Aug 2023

Cited by 3 | Viewed by 1640

Abstract

The main objective of this study consists in establishing the influence of the intergranular superdisintegrant on the specific properties of drotaverine hydrochloride fast-dissolving granules (DROT-FDGs) and orodispersible tablets (DROT-ODTs). The orodispersible tablets were obtained by the compression of the FDGs and excipient mixture with an eccentric tableting machine. To develop DROT-ODTs, two types of superdisintegrant excipients in different concentrations (water-soluble soy polysaccharides (SSP) (1%, 5%) and water-insoluble soy polysaccharides—Emcosoy^® STS IP (EMCS) (1%, 3%, 5%)) were used, resulting in five formulations (D1–D5). The DROT-FDGs and the DROT-ODTs were subjected to pharmacotechnical and analytical evaluation. All the orodispersible tablets obtained respect the quality requirements in terms of friability (less than 1%), crushing strength (ranging between 52 N for D2 and 125.5 N for D3), and disintegration time (<180 s). The in vitro release of drotaverine from ODTs showed that all formulations presented amounts of active substance released greater than 85% at 10 min. The main objective, developing 30 mg DROT-ODTs for children aged between 6 and 12 years by incorporating the API in FDGs, was successfully achieved. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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21 pages, 5204 KiB

Open AccessArticle

Laponite Composites: In Situ Films Forming as a Possible Healing Agent

by Ramón Andrés Pineda-Álvarez, Carolina Flores-Avila, Luis Medina-Torres, Jesús Gracia-Mora, José Juan Escobar-Chávez, Gerardo Leyva-Gómez, Mohammad-Ali Shahbazi and María Josefa Bernad-Bernad

Pharmaceutics 2023, 15(6), 1634; https://doi.org/10.3390/pharmaceutics15061634 - 31 May 2023

Cited by 2 | Viewed by 2097

Abstract

A healing material must have desirable characteristics such as maintaining a physiological environment, protective barrier-forming abilities, exudate absorption, easy handling, and non-toxicity. Laponite is a synthetic clay with properties such as swelling, physical crosslinking, rheological stability, and drug entrapment, making it an interesting alternative for developing new dressings. This study evaluated its performance in lecithin/gelatin composites (LGL) as well as with the addition of maltodextrin/sodium ascorbate mixture (LGL MAS). These materials were applied as nanoparticles, dispersed, and prepared by using the gelatin desolvation method—eventually being turned into films via the solvent-casting method. Both types of composites were also studied as dispersions and films. Dynamic Light Scattering (DLS) and rheological techniques were used to characterize the dispersions, while the films’ mechanical properties and drug release were determined. Laponite in an amount of 8.8 mg developed the optimal composites, reducing the particulate size and avoiding the agglomeration by its physical crosslinker and amphoteric properties. On the films, it enhanced the swelling and provided stability below 50 °C. Moreover, the study of drug release in maltodextrin and sodium ascorbate from LGL MAS was fitted to first-order and Korsmeyer–Peppas models, respectively. The aforementioned systems represent an interesting, innovative, and promising alternative in the field of healing materials. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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23 pages, 8303 KiB

Open AccessArticle

New Smart Bioactive and Biomimetic Chitosan-Based Hydrogels for Wounds Care Management

by Simona-Maria Tatarusanu, Alexandru Sava, Bianca-Stefania Profire, Tudor Pinteala, Alexandra Jitareanu, Andreea-Teodora Iacob, Florentina Lupascu, Natalia Simionescu, Irina Rosca and Lenuta Profire

Pharmaceutics 2023, 15(3), 975; https://doi.org/10.3390/pharmaceutics15030975 - 17 Mar 2023

Cited by 12 | Viewed by 3056

Abstract

Wound management represents a continuous challenge for health systems worldwide, considering the growing incidence of wound-related comorbidities, such as diabetes, high blood pressure, obesity, and autoimmune diseases. In this context, hydrogels are considered viable options since they mimic the skin structure and promote autolysis and growth factor synthesis. Unfortunately, hydrogels are associated with several drawbacks, such as low mechanical strength and the potential toxicity of byproducts released after crosslinking reactions. To overcome these aspects, in this study new smart chitosan (CS)-based hydrogels were developed, using oxidized chitosan (oxCS) and hyaluronic acid (oxHA) as nontoxic crosslinkers. Three active product ingredients (APIs) (fusidic acid, allantoin, and coenzyme Q10), with proven biological effects, were considered for inclusion in the 3D polymer matrix. Therefore, six API-CS-oxCS/oxHA hydrogels were obtained. The presence of dynamic imino bonds in the hydrogels’ structure, which supports their self-healing and self-adapting properties, was confirmed by spectral methods. The hydrogels were characterized by SEM, swelling degree, pH, and the internal organization of the 3D matrix was studied by rheological behavior. Moreover, the cytotoxicity degree and the antimicrobial effects were also investigated. In conclusion, the developed API-CS-oxCS/oxHA hydrogels have real potential as smart materials in wound management, based on their self-healing and self-adapting properties, as well as on the benefits of APIs. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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17 pages, 3689 KiB

Open AccessArticle

Polyethylenimine-Conjugated Hydroxyethyl Cellulose for Doxorubicin/Bcl-2 siRNA Co-Delivery Systems

by Jiwon Park, Seoyoung Kim and Tae-il Kim

Pharmaceutics 2023, 15(2), 708; https://doi.org/10.3390/pharmaceutics15020708 - 20 Feb 2023

Cited by 4 | Viewed by 2660

Abstract

Hydroxyethyl cellulose (HEC), widely known for its biocompatibility and water solubility, is a polysaccharide with potential for pharmaceutical applications. Here, we synthesized polyethylenimine2k (PEI2k)-conjugated hydroxyethyl cellulose (HECP2k) for doxorubicin/Bcl-2 siRNA co-delivery systems. HECP2ks were synthesized by reductive amination of PEI2k with periodate-oxidized HEC. The synthesis of the polymers was characterized using ¹H NMR, ¹³C NMR, primary amine quantification, FT-IR, and GPC. Via agarose gel electrophoresis and Zeta-sizer measurement, it was found that HECP2ks condensed pDNA to positively charged and nano-sized complexes (100–300 nm, ~30 mV). The cytotoxicity of HECP2ks was low and HECP2k 10X exhibited higher transfection efficiency than PEI25k even in serum condition, showing its high serum stability from ethylene oxide side chains. Flow cytometry analysis and confocal laser microscopy observation verified the superior cellular uptake and efficient endosome escape of HECP2k 10X. HECP2k 10X also could load Dox and Bcl-2 siRNA, forming nano-particles (HECP2k 10X@Dox/siRNA). By median effect analysis and annexin V staining analysis, it was found that HECP2k 10X@Dox/siRNA complexes could cause synergistically enhanced anti-cancer effects to cancer cells via induction of apoptosis. Consequently, it was concluded that HECP2k possesses great potential as a promising Dox/Bcl-2 siRNA co-delivery carrier. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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19 pages, 4822 KiB

Open AccessArticle

Novel Silicone-Grafted Alginate as a Drug Delivery Scaffold: Pharmaceutical Characterization of Gliclazide-Loaded Silicone-Based Composite Microcapsules

by Ahmed Gedawy, Giuseppe Luna, Jorge Martinez, Daniel Brown, Hani Al-Salami and Crispin R. Dass

Pharmaceutics 2023, 15(2), 530; https://doi.org/10.3390/pharmaceutics15020530 - 4 Feb 2023

Cited by 3 | Viewed by 2535

Abstract

A novel gliclazide-loaded elastomeric carbohydrate pharmaceutical vehicle was successfully developed. This new siliconized alginate platform showed pseudoplastic rheology with a zeta potential ranging from (−43.8 mV to −75.5 mV). A Buchi-B390 encapsulator was employed to formulate different types of silicone-grafted alginate microcapsules loaded with gliclazide relying on the vibrational ionic gelation technology. The use of tetraethyl orthosilicate (TEOS) to crosslink the silicone elastomer (hydroxy terminated polydimethylsiloxane) of this new platform had improved the gliclazide encapsulation (>92.13% ± 0.76) of the free-flowing composite microcapsules, which showed good mechanical durability (up to 12 h in PBS pH 6.8) and promising results to sustain the drug release. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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18 pages, 2983 KiB

Open AccessArticle

In Vitro and In Vivo Biological Assays of Dextran Coated Iron Oxide Aqueous Magnetic Fluids

by Silviu-Adrian Predoi, Simona Liliana Iconaru and Daniela Predoi

Pharmaceutics 2023, 15(1), 177; https://doi.org/10.3390/pharmaceutics15010177 - 4 Jan 2023

Cited by 6 | Viewed by 2244

Abstract

The iron oxide nanoparticles coated with different surface coatings were studied and characterized by multiple physicochemical and biological methods. The present paper aims at estimating the toxicity in vitro and in vivo of dextran coated iron oxide aqueous magnetic fluids. The in vitro studies were conducted by quantifying the viability of HeLa cells after their incubation with the samples (concentrations of 62.5–125–250–500 μg/mL at different time intervals). The estimation of the toxicity in vivo of administering dextran coated iron oxide aqueous magnetic fluids (DIO-AMF) with hydrodynamic diameter of 25.73 ± 4 nm to Male Brown Norway rats has been made. Different concentrations (62.5–125–250–500 μg/mL) of dextran coated iron oxide aqueous magnetic fluids were administered for 7 consecutive days. Hematology and biochemistry of the Male Brown Norway rats assessment was performed at various time intervals (24–72 h and 21–28 days) after intra-peritoneal injection. The results showed that high concentrations of DIO-AMF (250 and 500 μg/mL) significantly increased white blood cells, red blood cells, hemoglobin and hematocrit compared to the values obtained for the control group (p < 0.05). Moreover, following the administration of DIO-AMF, the levels of alkaline phosphatase and aspartate aminotransferase increased compared to the control group (p < 0.05). After DIO-AMF administration, no significant difference was observed in the levels of alanine aminotransferase, gamma-glutamyl transpeptidase, urea and creatinine compared to the control group (p < 0.05). The results of the present study showed that dextran coated iron oxide aqueous magnetic fluids in concentrations lower than 250 μg/mL are reliable for medical and pharmaceutical applications. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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Review

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42 pages, 4436 KiB

Open AccessEditor’s ChoiceReview

Polysaccharide-Based Coatings as Drug Delivery Systems

by Anita Ioana Visan and Rodica Cristescu

Pharmaceutics 2023, 15(9), 2227; https://doi.org/10.3390/pharmaceutics15092227 - 29 Aug 2023

Cited by 16 | Viewed by 2955

Abstract

Therapeutic polysaccharide-based coatings have recently emerged as versatile strategies to transform a conventional medical implant into a drug delivery system. However, the translation of these polysaccharide-based coatings into the clinic as drug delivery systems still requires a deeper understanding of their drug degradation/release profiles. This claim is supported by little or no data. In this review paper, a comprehensive description of the benefits and challenges generated by the polysaccharide-based coatings is provided. Moreover, the latest advances made towards the application of the most important representative coatings based on polysaccharide types for drug delivery are debated. Furthermore, suggestions/recommendations for future research to speed up the transition of polysaccharide-based drug delivery systems from the laboratory testing to clinical applications are given. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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30 pages, 2546 KiB

Open AccessEditor’s ChoiceReview

Contemporary Aspects of Designing Marine Polysaccharide Microparticles as Drug Carriers for Biomedical Application

by Paolina Lukova and Plamen Katsarov

Pharmaceutics 2023, 15(8), 2126; https://doi.org/10.3390/pharmaceutics15082126 - 11 Aug 2023

Cited by 6 | Viewed by 1755

Abstract

The main goal of modern pharmaceutical technology is to create new drug formulations that are safer and more effective. These formulations should allow targeted drug delivery, improved drug stability and bioavailability, fewer side effects, and reduced drug toxicity. One successful approach for achieving these objectives is using polymer microcarriers for drug delivery. They are effective for treating various diseases through different administration routes. When creating pharmaceutical systems, choosing the right drug carrier is crucial. Biomaterials have become increasingly popular over the past few decades due to their lack of toxicity, renewable sources, and affordability. Marine polysaccharides, in particular, have been widely used as substitutes for synthetic polymers in drug carrier applications. Their inherent properties, such as biodegradability and biocompatibility, make marine polysaccharide-based microcarriers a prospective platform for developing drug delivery systems. This review paper explores the principles of microparticle design using marine polysaccharides as drug carriers. By reviewing the current literature, the paper highlights the challenges of formulating polymer microparticles, and proposes various technological solutions. It also outlines future perspectives for developing marine polysaccharides as drug microcarriers. Full article

(This article belongs to the Special Issue Carbohydrate-Based Carriers for Drug Delivery)

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