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28 pages, 6676 KiB

Open AccessArticle

Multifunctional Hydrogels Based on Cellulose and Modified Lignin for Advanced Wounds Management

by Diana Elena Ciolacu, Raluca Nicu, Dana Mihaela Suflet, Daniela Rusu, Raluca Nicoleta Darie-Nita, Natalia Simionescu, Georgeta Cazacu and Florin Ciolacu

Pharmaceutics 2023, 15(11), 2588; https://doi.org/10.3390/pharmaceutics15112588 - 04 Nov 2023

Cited by 2 | Viewed by 986

Abstract

Considering the complex process of wound healing, it is expected that an optimal wound dressing should be able to overcome the multiple obstacles that can be encountered in the wound healing process. An ideal dressing should be biocompatible, biodegradable and able to maintain [...] Read more.

Considering the complex process of wound healing, it is expected that an optimal wound dressing should be able to overcome the multiple obstacles that can be encountered in the wound healing process. An ideal dressing should be biocompatible, biodegradable and able to maintain moisture, as well as allow the removal of exudate, have antibacterial properties, protect the wound from pathogens and promote wound healing. Starting from this desideratum, we intended to design a multifunctional hydrogel that would present good biocompatibility, the ability to provide a favorable environment for wound healing, antibacterial properties, and also, the capacity to release drugs in a controlled manner. In the preparation of hydrogels, two natural polymers were used, cellulose (C) and chemically modified lignin (LE), which were chemically cross-linked in the presence of epichlorohydrin. The structural and morphological characterization of CLE hydrogels was performed by ATR-FTIR spectroscopy and scanning electron microscopy (SEM), respectively. In addition, the degree of swelling of CLE hydrogels, the incorporation/release kinetics of procaine hydrochloride (PrHy), and their cytotoxicity and antibacterial properties were investigated. The rheological characterization, mechanical properties and mucoadhesion assessment completed the study of CLE hydrogels. The obtained results show that CLE hydrogels have an increased degree of swelling compared to cellulose-based hydrogel, a better capacity to encapsulate PrHy and to control the release of the drug, as well as antibacterial properties and improved mucoadhesion. All these characteristics highlight that the addition of LE to the cellulose matrix has a positive impact on the properties of CLE hydrogels, confirming that these hydrogels can be considered as potential candidates for applications as oral wound dressings. Full article

(This article belongs to the Special Issue Recent Advances in Pharmaceutical Applications of Functionalized Polysaccharides and Their Derivatives)

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20 pages, 6216 KiB

Open AccessArticle

Novel Green Crosslinked Salecan Hydrogels and Preliminary Investigation of Their Use in 3D Printing

by Raluca Ianchis, Rebeca Leu Alexa, Ioana Catalina Gifu, Maria Minodora Marin, Elvira Alexandrescu, Roxana Constantinescu, Andrada Serafim, Cristina Lavinia Nistor and Cristian Petcu

Pharmaceutics 2023, 15(2), 373; https://doi.org/10.3390/pharmaceutics15020373 - 21 Jan 2023

Cited by 6 | Viewed by 1749

Abstract

Salecan, a kind of polysaccharide, is produced by the Agrobacterium ZX09 salt tolerant strain. In this study, green crosslinked citric acid-salecan hydrogels are explored as novel materials with a high potential for use in regenerative medicine. The impact of salecan and citric acid [...] Read more.

Salecan, a kind of polysaccharide, is produced by the Agrobacterium ZX09 salt tolerant strain. In this study, green crosslinked citric acid-salecan hydrogels are explored as novel materials with a high potential for use in regenerative medicine. The impact of salecan and citric acid on the final crosslinked hydrogels was intensively studied and estimated in terms of the whole physicochemical properties and antimicrobial activity. FTIR spectra demonstrated the successful green crosslinking of salecan through its esterification with citric acid where the formation of strong covalent bonds collaboratively helped to stabilize the entire hydrogel systems in a wet state. Hydrogels presented a microporous morphology, good swelling capacity, pH responsiveness, great mechanical stability under stress conditions and good antibacterial activity, all related to the concentration of the biopolymers used in the synthesis step. Additionally, salecan hydrogels were preliminary investigated as printing inks. Thanks to their excellent rheological behavior, we optimized the citrate-salecan hydrogel inks and printing parameters to render 3D constructs with great printing fidelity and integrity. The novel synthesized salecan green crosslinked hydrogels enriches the family of salecan-derived hydrogels. Moreover, this work not only expands the application of salecan hydrogels in various fields, but also provides a new potential option of designing salecan-based 3D printed scaffolds for customized regenerative medicine. Full article

(This article belongs to the Special Issue Recent Advances in Pharmaceutical Applications of Functionalized Polysaccharides and Their Derivatives)

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24 pages, 7183 KiB

Open AccessArticle

Hyaluronic Acid-Modified Cisplatin-Encapsulated Poly(Lactic-co-Glycolic Acid) Magnetic Nanoparticles for Dual-Targeted NIR-Responsive Chemo-Photothermal Combination Cancer Therapy

by Huai-An Chen, Yu-Jen Lu, Banendu Sunder Dash, Yin-Kai Chao and Jyh-Ping Chen

Pharmaceutics 2023, 15(1), 290; https://doi.org/10.3390/pharmaceutics15010290 - 14 Jan 2023

Cited by 12 | Viewed by 2575

Abstract

Combination chemo-photothermal therapy with nanomaterials can reduce the dose of chemotherapeutic drugs required for effective cancer treatment by minimizing toxic side effects while improving survival times. Toward this end, we prepare hyaluronic acid (HA)-modified poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (MNP) for the CD44 [...] Read more.

Combination chemo-photothermal therapy with nanomaterials can reduce the dose of chemotherapeutic drugs required for effective cancer treatment by minimizing toxic side effects while improving survival times. Toward this end, we prepare hyaluronic acid (HA)-modified poly(lactic-co-glycolic acid) (PLGA) magnetic nanoparticles (MNP) for the CD44 receptor-mediated and magnetic field-guided dual-targeted delivery of cisplatin (CDDP). By co-encapsulating the CDDP and oleic acid-coated iron oxide MNP (IOMNP) in PLGA, the PMNPc was first prepared in a single emulsification/solvent evaporation step and successively surface modified with chitosan and HA to prepare the HA/PMNPc. Spherical HA/PMNPc nanoparticles of ~300 nm diameter can be prepared with 18 and 10% (w/w) loading content of CDDP and IOMNP and a pH-sensitive drug release to facilitate the endosomal release of the CDDP after intracellular uptake. This leads to the higher cytotoxicity of the HA/PMNPc toward the U87 glioblastoma cells than free CDDP with reduced IC50, a higher cell apoptosis rate, and the enhanced expression of cell apoptosis marker proteins. Furthermore, the nanoparticles show the hyperthermia effect toward U87 after short-term near-infrared (NIR) light exposure, which can further elevate the cell apoptosis/necrosis rate and upregulate the HSP70 protein expression due to the photothermal effects. The combined cancer therapeutic efficacy was studied in vivo using subcutaneously implanted U87 cells in nude mice. By using dual-targeted chemo-photothermal combination cancer therapy, the intravenously injected HA/PMNPc under magnetic field guidance and followed by NIR laser irradiation was demonstrated to be the most effective treatment modality by inhibiting the tumor growth and prolonging the survival time of the tumor-bearing nude mice. Full article

(This article belongs to the Special Issue Recent Advances in Pharmaceutical Applications of Functionalized Polysaccharides and Their Derivatives)

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16 pages, 2117 KiB

Open AccessFeature PaperArticle

Central Composite Design for Optimization of Mitomycin C-Loaded Quantum Dots/Chitosan Nanoparticles as Drug Nanocarrier Vectors

by Fariza Aina Abd Manan, Nor Azah Yusof, Jaafar Abdullah and Armania Nurdin

Pharmaceutics 2023, 15(1), 209; https://doi.org/10.3390/pharmaceutics15010209 - 06 Jan 2023

Cited by 1 | Viewed by 1806

Abstract

Cancer is one of the most devastating diseases that leads to a high degree of mortality worldwide. Hence, extensive efforts have been devoted to the development of drug nanocarrier vectors as a potential new cancer treatment option. The main goal of this treatment [...] Read more.

Cancer is one of the most devastating diseases that leads to a high degree of mortality worldwide. Hence, extensive efforts have been devoted to the development of drug nanocarrier vectors as a potential new cancer treatment option. The main goal of this treatment is to deliver an anticancer medicine successfully and effectively to the patient’s cells using non-toxic nanocarriers. Here, we present a drug delivery system to emphasize the optimization of an anticancer drug-loaded formulation using Mitomycin C (MMC) encapsulated in chitosan nanocarrier conjugated with a bioimaging fluorescence probe of Mn:ZnS quantum dots (MMC@CS-Mn:ZnS). Additionally, the Response Surface Methodology (RSM), which uses a quadratic model to forecast the behaviour of the nano-drug delivery system, was used to assess the optimization of encapsulation efficiency. In this investigation, the core points of the Central Composite Design (CCD) model were used with 20 runs and 6 replications. The encapsulation efficiency (EE%) was measured using UV-Vis spectroscopy at 362 nm. The highest EE% is 55.31 ± 3.09 under the optimum parameters of incubation time (105 min), concentration of MMC (0.875 mg/mL), and concentration of nanocarriers (5.0 mg/mL). Physicochemical characterizations for the nanocarriers were accessed using a nanosizer and field-emission scanning electron microscopy (FESEM). Three independent variables for the evaluation of the encapsulation efficiency were used, in which the incubation time, concentration of MMC, concentration of nanocarriers, and correlation for each variable were studied. Furthermore, the MMC drug release efficiency was carried out in four different solution pHs of 5.5, 6.0, 6.5, 7.0, and pH 7.5, and the highest cumulative drug release of 81.44% was obtained in a pH 5.5 release medium, followed by cumulative releases of 68.55%, 50.91%, 41.57%, and 32.45% in release mediums with pH 6.0, pH 6.5, pH 7.0, and pH 7.5. Subsequently, five distinct mathematical models—pseudo-first-order, pseudo-second-order, Hixson-Crowell, Korsmeyer-Peppas, and Higuchi kinetic models—were used to fit all of the drug release data. The Korsmeyers-Peppas model was found to fit it well, highlighting its importance for the log of cumulative drug release proportional to the log of time at the equilibrium state. The correlation coefficient value (R²) was obtained as 0.9527, 0.9735, 0.9670, 0.9754, and 0.9639 for the drug release in pH 5.5, pH 6.0, pH 6.5, pH 7.0, and pH 7.5, respectively. Overall, from the analysis, the as-synthesized MMC nanocarrier (MMC@CS-Mn:ZnS) synergistically elucidates the underlying efficient delivery of MMC and leverages the drug loading efficiency, and all these factors have the potential for the simultaneous curbing of non-muscle invasive bladder cancer reoccurrence and progression when applied to the real-time disease treatment. Full article

(This article belongs to the Special Issue Recent Advances in Pharmaceutical Applications of Functionalized Polysaccharides and Their Derivatives)

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24 pages, 2669 KiB

Open AccessArticle

Folic Acid-Grafted Chitosan-Alginate Nanocapsules as Effective Targeted Nanocarriers for Delivery of Turmeric Oil for Breast Cancer Therapy

by Htet Htet Moe San, Khent Primo Alcantara, Bryan Paul I. Bulatao, Feuangthit Niyamissara Sorasitthiyanukarn, Nonthaneth Nalinratana, Apichart Suksamrarn, Opa Vajragupta, Pranee Rojsitthisak and Pornchai Rojsitthisak

Pharmaceutics 2023, 15(1), 110; https://doi.org/10.3390/pharmaceutics15010110 - 28 Dec 2022

Cited by 8 | Viewed by 2232

Abstract

Folate receptors (FRs) highly expressed in breast cancers can be used as a recognized marker for preventing off-target delivery of chemotherapeutics. In this study, folic acid (FA)-grafted chitosan-alginate nanocapsules (CS-Alg-NCs) loaded with turmeric oil (TO) were developed for breast cancer targeting. CS was [...] Read more.

Folate receptors (FRs) highly expressed in breast cancers can be used as a recognized marker for preventing off-target delivery of chemotherapeutics. In this study, folic acid (FA)-grafted chitosan-alginate nanocapsules (CS-Alg-NCs) loaded with turmeric oil (TO) were developed for breast cancer targeting. CS was successfully conjugated with FA via an amide bond with a degree of substitution at 12.86%. The TO-loaded FA-grafted CS-Alg-NCs (TO-FA-CS-Alg-NCs) optimized by Box-Behnken design using response surface methodology had satisfactory characteristics with homogenous particle size (189 nm) and sufficient encapsulation efficiency and loading capacity (35.9% and 1.82%, respectively). In vitro release study of the optimized TO-FA-CS-Alg-NCs showed a sustained TO release following the Korsmeyer-Peppas model with a Fickian diffusion mechanism at pH 5.5 and 7.4. The TO-FA-CS-Alg-NCs showed lower IC₅₀ than ungrafted TO-CS-Alg-NCs and unencapsulated TO against MDA-MB-231 and MCF-7 breast cancer cells, suggesting that FA-CS-Alg-NCs can improve anticancer activity of TO through its active targeting to the high FRs expressing breast cancers. Full article

(This article belongs to the Special Issue Recent Advances in Pharmaceutical Applications of Functionalized Polysaccharides and Their Derivatives)

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14 pages, 15124 KiB

Open AccessArticle

Synthesis and Rheological Characterization of a Novel Salecan Hydrogel

by Qinling Zhang, Teng Ren, Jing Gan, Lirong Sun, Chenxia Guan, Qian Zhang, Shihui Pan and Hao Chen

Pharmaceutics 2022, 14(7), 1492; https://doi.org/10.3390/pharmaceutics14071492 - 18 Jul 2022

Cited by 8 | Viewed by 1813

Abstract

Salecan (Sal) is a novel microbial polysaccharide. In the present research, thermal treatment was performed to fabricate Sal hydrogel. The effect of Sal concentration on water holding capacity, swelling properties, texture properties, and microstructure of the hydrogels was discussed. It was found that [...] Read more.

Salecan (Sal) is a novel microbial polysaccharide. In the present research, thermal treatment was performed to fabricate Sal hydrogel. The effect of Sal concentration on water holding capacity, swelling properties, texture properties, and microstructure of the hydrogels was discussed. It was found that the equilibrium degree of swelling (EDS) of Sal hydrogels was above 1500%, inferred Sal was a highly hydrophilic polysaccharide. As Sal concentration increased from 3.5 to 8.0 wt%, the hardness increased from 0.88 to 2.07 N and the water hold capability (WHC) increased from 91.3% to 98.2%. Furthermore, the internal network structure of Sal hydrogel also became denser and more uniform. Rheological studies suggested that elastic hydrogel formed under the gelation process. All these results demonstrated that Sal hydrogel prepared by thermal treatment had good gelling properties, which opened up a new safe way for the preparation of Sal hydrogel and broadened the application range of Sal. Full article

(This article belongs to the Special Issue Recent Advances in Pharmaceutical Applications of Functionalized Polysaccharides and Their Derivatives)

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Review

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33 pages, 11887 KiB

Open AccessReview

Chitosan-Based Biomaterials for Tissue Regeneration

by Yevgeniy Kim, Zharylkasyn Zharkinbekov, Kamila Raziyeva, Laura Tabyldiyeva, Kamila Berikova, Dias Zhumagul, Kamila Temirkhanova and Arman Saparov

Pharmaceutics 2023, 15(3), 807; https://doi.org/10.3390/pharmaceutics15030807 - 01 Mar 2023

Cited by 35 | Viewed by 5026

Abstract

Chitosan is a chitin-derived biopolymer that has shown great potential for tissue regeneration and controlled drug delivery. It has numerous qualities that make it attractive for biomedical applications such as biocompatibility, low toxicity, broad-spectrum antimicrobial activity, and many others. Importantly, chitosan can be [...] Read more.

Chitosan is a chitin-derived biopolymer that has shown great potential for tissue regeneration and controlled drug delivery. It has numerous qualities that make it attractive for biomedical applications such as biocompatibility, low toxicity, broad-spectrum antimicrobial activity, and many others. Importantly, chitosan can be fabricated into a variety of structures including nanoparticles, scaffolds, hydrogels, and membranes, which can be tailored to deliver a desirable outcome. Composite chitosan-based biomaterials have been demonstrated to stimulate in vivo regeneration and the repair of various tissues and organs, including but not limited to, bone, cartilage, dental, skin, nerve, cardiac, and other tissues. Specifically, de novo tissue formation, resident stem cell differentiation, and extracellular matrix reconstruction were observed in multiple preclinical models of different tissue injuries upon treatment with chitosan-based formulations. Moreover, chitosan structures have been proven to be efficient carriers for medications, genes, and bioactive compounds since they can maintain the sustained release of these therapeutics. In this review, we discuss the most recently published applications of chitosan-based biomaterials for different tissue and organ regeneration as well as the delivery of various therapeutics. Full article

(This article belongs to the Special Issue Recent Advances in Pharmaceutical Applications of Functionalized Polysaccharides and Their Derivatives)

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19 pages, 2162 KiB

Open AccessReview

Advances in Chitosan-Based CRISPR/Cas9 Delivery Systems

by Anna E. Caprifico, Peter J. S. Foot, Elena Polycarpou and Gianpiero Calabrese

Pharmaceutics 2022, 14(9), 1840; https://doi.org/10.3390/pharmaceutics14091840 - 01 Sep 2022

Cited by 11 | Viewed by 2155

Abstract

Clustered regularly interspaced short palindromic repeat (CRISPR) and the associated Cas endonuclease (Cas9) is a cutting-edge genome-editing technology that specifically targets DNA sequences by using short RNA molecules, helping the endonuclease Cas9 in the repairing of genes responsible for genetic diseases. However, the [...] Read more.

Clustered regularly interspaced short palindromic repeat (CRISPR) and the associated Cas endonuclease (Cas9) is a cutting-edge genome-editing technology that specifically targets DNA sequences by using short RNA molecules, helping the endonuclease Cas9 in the repairing of genes responsible for genetic diseases. However, the main issue regarding the application of this technique is the development of an efficient CRISPR/Cas9 delivery system. The consensus relies on the use of non-viral delivery systems represented by nanoparticles (NPs). Chitosan is a safe biopolymer widely used in the generation of NPs for several biomedical applications, especially gene delivery. Indeed, it shows several advantages in the context of gene delivery systems, for instance, the presence of positively charged amino groups on its backbone can establish electrostatic interactions with the negatively charged nucleic acid forming stable nanocomplexes. However, its main limitations include poor solubility in physiological pH and limited buffering ability, which can be overcome by functionalising its chemical structure. This review offers a critical analysis of the different approaches for the generation of chitosan-based CRISPR/Cas9 delivery systems and suggestions for future developments. Full article

(This article belongs to the Special Issue Recent Advances in Pharmaceutical Applications of Functionalized Polysaccharides and Their Derivatives)

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