Research

Jump to: Review

22 pages, 5494 KiB

Open AccessArticle

Protein Adsorption, Calcium-Binding Ability, and Biocompatibility of Silver Nanoparticle-Loaded Polyvinyl Alcohol (PVA) Hydrogels Using Bone Marrow-Derived Mesenchymal Stem Cells

by Jeevithan Elango, Camilo Zamora-Ledezma, Frank Alexis, Wenhui Wu and José Eduardo Maté-Sánchez de Val

Pharmaceutics 2023, 15(7), 1843; https://doi.org/10.3390/pharmaceutics15071843 - 28 Jun 2023

Cited by 1 | Viewed by 1455

Abstract

Several approaches have evolved to facilitate the exploration of hydrogel systems in biomedical research. In this sense, poly(vinyl alcohol) (PVA) has been widely used in hydrogel (HG) fabrication for several therapeutic applications. The biological properties of PVA hydrogels (PVA-HGs) are highly dependent on [...] Read more.

Several approaches have evolved to facilitate the exploration of hydrogel systems in biomedical research. In this sense, poly(vinyl alcohol) (PVA) has been widely used in hydrogel (HG) fabrication for several therapeutic applications. The biological properties of PVA hydrogels (PVA-HGs) are highly dependent on their interaction with protein receptors and extracellular matrix (mainly calcium) deposition, for which there is not enough evidence from existing research yet. Thus, for the first time, the functional properties, like protein and mineral interactions, related to the proliferation of mesenchymal stem cells (MSCs) by silver nanoparticle (AgNP)-loaded PVA hydrogels (AgNPs-PVA-HGs) were investigated in the present study. The UV absorption spectrum and TEM microscopic results showed a maximum absorbance of synthesized AgNPs at 409 nm, with an average particle size of 14.5 ± 2.5 nm, respectively. The functional properties, such as the calcium-binding and the protein adsorption of PVA-HG, were accelerated by incorporating AgNPs; however, the swelling properties of the HGs were reduced by AgNPs, which might be due to the masking of the free functional groups (hydroxyl groups of PVA) by AgNPs. SEM images showed the presence of AgNPs with a more porous structure in the HGs. The proliferative effect of MSCs increased over culture time from day 1 to day 7, and the cell proliferative effect was upregulated by HGs with more pronounced AgNPs-PVA-HG. In addition, both HGs did not produce any significant cytotoxicity in the MSCs. The histological (bright light and H&E staining) and fluorescence microscopic images showed the presence of a cytoskeleton and the fibrillar structure of the MSCs, and the cells adhered more firmly to all HGs. More fibrillar bipolar and dense fibrillar structures were seen in the day 1 and day 7 cultures, respectively. Interestingly, the MSCs cultured on AgNPs-PVA-HG produced extracellular matrix deposition on day 7. Accordingly, the present results proved the biocompatibility of AgNPs-PVA-HG as a suitable system for culturing mammalian stem cells for regenerative tissue applications. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

17 pages, 9050 KiB

Open AccessArticle

Proliferative and Osteogenic Supportive Effect of VEGF-Loaded Collagen-Chitosan Hydrogel System in Bone Marrow Derived Mesenchymal Stem Cells

by Jeevithan Elango

Pharmaceutics 2023, 15(4), 1297; https://doi.org/10.3390/pharmaceutics15041297 - 20 Apr 2023

Cited by 6 | Viewed by 1379

Abstract

The use of hydrogel (HG) in regenerative medicine is an emerging field and thus several approaches have been proposed recently to find an appropriate hydrogel system. In this sense, this study developed a novel HG system using collagen, chitosan, and VEGF composites for [...] Read more.

The use of hydrogel (HG) in regenerative medicine is an emerging field and thus several approaches have been proposed recently to find an appropriate hydrogel system. In this sense, this study developed a novel HG system using collagen, chitosan, and VEGF composites for culturing mesenchymal stem cells (MSCs), and investigated their ability for osteogenic differentiation and mineral deposition. Our results showed that the HG loaded with 100 ng/mL VEGF (HG-100) significantly supported the proliferation of undifferentiated MSCs, the fibrillary filament structure (HE stain), mineralization (alizarin red S and von Kossa stain), alkaline phosphatase, and the osteogenesis of differentiated MSCs compared to other hydrogels (loaded with 25 and 50 ng/mL VEGF) and control (without hydrogel). HG-100 showed a higher VEGF releasing rate from day 3 to day 7 than other HGs, which substantially supports the proliferative and osteogenic properties of HG-100. However, the HGs did not increase the cell growth in differentiated MSCs on days 14 and 21 due to the confluence state (reach stationary phase) and cell loading ability, regardless of the VEGF content. Similarly, the HGs alone did not stimulate the osteogenesis of MSCs; however, they increased the osteogenic ability of MSCs in presence of osteogenic supplements. Accordingly, a fabricated HG with VEGF could be used as an appropriate system to culture stem cells for bone and dental regeneration. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

14 pages, 4642 KiB

Open AccessArticle

pH-Responsive Super-Porous Hybrid Hydrogels for Gastroretentive Controlled-Release Drug Delivery

by Ajkia Zaman Juthi, Fenfen Li, Bo Wang, Md Mofasserul Alam, Md Eman Talukder and Bensheng Qiu

Pharmaceutics 2023, 15(3), 816; https://doi.org/10.3390/pharmaceutics15030816 - 02 Mar 2023

Cited by 4 | Viewed by 1817

Abstract

Super-porous hydrogels are considered a potential drug delivery network for the sedation of gastric mechanisms with retention windows in the abdomen and upper part of the gastrointestinal tract (GIT). In this study, a novel pH-responsive super-porous hybrid hydrogels (SPHHs) was synthesized from pectin, [...] Read more.

Super-porous hydrogels are considered a potential drug delivery network for the sedation of gastric mechanisms with retention windows in the abdomen and upper part of the gastrointestinal tract (GIT). In this study, a novel pH-responsive super-porous hybrid hydrogels (SPHHs) was synthesized from pectin, poly 2-hydroxyethyl methacrylate (2HEMA), and N, N methylene-bis-acrylamide (BIS) via the gas-blowing technique, and then loaded with a selected drug (amoxicillin trihydrate, AT) at pH 5 via an aqueous loading method. The drug-loaded SPHHs-AT carrier demonstrated outstanding (in vitro) gastroretentive drug delivery capability. The study attributed excellent swelling and delayed drug release to acidic conditions at pH 1.2. Moreover, in vitro controlled-release drug delivery systems at different pH values, namely, 1.2 (97.99%) and 7.4 (88%), were studied. These exceptional features of SPHHs—improved elasticity, pH responsivity, and high swelling performance—should be investigated for broader drug delivery applications in the future. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Graphical abstract

18 pages, 8703 KiB

Open AccessArticle

Chitosan-Dextran-Glycerol Hydrogels Loaded with Iron Oxide Nanoparticles for Wound Dressing Applications

by Cristina Chircov, Iuliana Teodora Bejenaru, Adrian Ionuț Nicoară, Alexandra Cătălina Bîrcă, Ovidiu Cristian Oprea and Bianca Tihăuan

Pharmaceutics 2022, 14(12), 2620; https://doi.org/10.3390/pharmaceutics14122620 - 28 Nov 2022

Cited by 10 | Viewed by 2095

Abstract

Natural polymers have shown tremendous potential towards the development of hydrogels with tissue regeneration properties. Among them, chitosan and dextran are polysaccharides widely applied in the wound dressing area owing to their mucoadhesiveness, biodegradability, hemostatic potential, and intrinsic antibacterial activity, while glycerol is [...] Read more.

Natural polymers have shown tremendous potential towards the development of hydrogels with tissue regeneration properties. Among them, chitosan and dextran are polysaccharides widely applied in the wound dressing area owing to their mucoadhesiveness, biodegradability, hemostatic potential, and intrinsic antibacterial activity, while glycerol is a well-known biocompatible solvent extensively used in the manufacture of cosmetic, pharmaceutical, medical, and personal care products. In order to enhance the properties of natural polymer-based hydrogels, the focus has currently shifted towards the addition of nanomaterials with antibacterial and regenerative potential, i.e., iron oxide nanoparticles. Thus, the aim of the present study was to develop a series of chitosan-dextran-glycerol hydrogels loaded with iron oxide nanoparticles, either readily added or formed in situ. The physicochemical properties of the so obtained hydrogels demonstrated an improved dispersibility of the in situ formed magnetite nanoparticles, which further decreases the porosity and swelling ratio of the hydrogels but increases the antimicrobial properties. Additionally, the presence of glycerol enhances the cell viability but reduces the antimicrobial potential. In this context, the results proved promising biological and antimicrobial properties, thus confirming their potential as biomaterials for wound healing and regeneration. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

19 pages, 4257 KiB

Open AccessArticle

A Simple Preparation Method of Gelatin Hydrogels Incorporating Cisplatin for Sustained Release

by Takahisa Suzuki, Shigeru Tsunoda, Kota Yamashita, Toshie Kuwahara, Mitsuru Ando, Yasuhiko Tabata and Kazutaka Obama

Pharmaceutics 2022, 14(12), 2601; https://doi.org/10.3390/pharmaceutics14122601 - 25 Nov 2022

Cited by 1 | Viewed by 1927

Abstract

The objective of this study was to develop a new preparation method for cisplatin (CDDP)-incorporated gelatin hydrogels without using chemical crosslinking nor a vacuum heating instrument for dehydrothermal crosslinking. By simply mixing CDDP and gelatin, CDDP-crosslinked gelatin hydrogels (CCGH) were prepared. CDDP functions [...] Read more.

The objective of this study was to develop a new preparation method for cisplatin (CDDP)-incorporated gelatin hydrogels without using chemical crosslinking nor a vacuum heating instrument for dehydrothermal crosslinking. By simply mixing CDDP and gelatin, CDDP-crosslinked gelatin hydrogels (CCGH) were prepared. CDDP functions as a crosslinking agent of gelatin to form the gelatin hydrogel. Simultaneously, CDDP is incorporated into the gelatin hydrogel as a controlled release carrier. CDDP’s in vitro and in vivo anticancer efficacy after incorporation into CCGH was evaluated. In the in vitro system, the CDDP was released gradually due to CCGH degradation with an initial burst release of approximately 16%. CDDP metal-coordinated with the degraded fragment of gelatin was released from CCGH with maintaining the anticancer activity. After intraperitoneal administration of CCGH, CDDP was detected in the blood circulation while its toxicity was low. Following intraperitoneal administration of CCGH in a murine peritoneal dissemination model of human gastric cancer MKN45-Luc cell line, the survival time was significantly prolonged compared with free CDDP solution. It is concluded that CCGH prepared by the CDDP-based crosslinking of gelatin is an excellent sustained release system of CDDP to achieve superior anticancer effects with minimal side effects compared with free CDDP solution. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

24 pages, 5836 KiB

Open AccessArticle

Mutual Jellification of Two Bactericidal Cationic Polymers: Synthesis and Physicochemical Characterization of a New Two-Component Hydrogel

by Silvana Alfei, Alessia Zorzoli, Danilo Marimpietri, Anna Maria Schito and Eleonora Russo

Pharmaceutics 2022, 14(11), 2444; https://doi.org/10.3390/pharmaceutics14112444 - 11 Nov 2022

Cited by 3 | Viewed by 1092

Abstract

Here, a new two-component hydrogel (CP1OP2-Hgel) was developed, simply by dispersing in water two cationic bactericidal polymers (CP1 and OP2) effective against several multidrug-resistant (MDR) clinical isolates of the most relevant Gram-positive and Gram-negative species. Interestingly, while OP2 acts only as an antibacterial [...] Read more.

Here, a new two-component hydrogel (CP1OP2-Hgel) was developed, simply by dispersing in water two cationic bactericidal polymers (CP1 and OP2) effective against several multidrug-resistant (MDR) clinical isolates of the most relevant Gram-positive and Gram-negative species. Interestingly, while OP2 acts only as an antibacterial ingredient when in gel, CP1 works as both an antibacterial and a gelling agent. To verify whether it would be worthwhile to use CP1 and OP2 as bioactive ingredients of a new hydrogel supposed for a future treatment of skin infections, dose-dependent cytotoxicity studies with CP1 and OP2 were performed on human fibroblasts for 24 h, before preparing the formulation. Although a significant cytotoxicity at concentrations > 2 µM was evidenced for both polymers, selectivity indices (SIs) over 12 (CP1) and up to six (OP2) were determined, due to the powerful antibacterial properties of the two polymers, thus supporting the rationale for their formulation as a hydrogel. The chemical structure and morphology of CP1OP2-Hgel were investigated by PCA-assisted attenuated total reflectance (ATR) Fourier-transform infrared (FTIR) analysis and scanning electron microscopy (SEM), while its rheological properties were assessed by determining its dynamic viscosity. The cumulative weight loss and swelling percentage curves, the porosity, and the maximum swelling capability of CP1OP2-Hgel were also determined and reported. Overall, due to the potent bactericidal effects of CP1 and OP2 and their favorable selectivity indices against several MDR pathogens, good rheological properties, high porosity, and strong swelling capability, CP1OP2-Hgel may, in the future, become a new weapon for treating severe nosocomial skin infections or infected chronic wounds. Further investigations in this sense are currently being carried out. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Graphical abstract

16 pages, 1546 KiB

Open AccessArticle

Towards the Preparation of a Hydrogel from Lyophilisates of the Aloe arborescens Aqueous Extract

by Kamil Pawłowicz, Magdalena Paczkowska-Walendowska, Tomasz Osmałek and Judyta Cielecka-Piontek

Pharmaceutics 2022, 14(7), 1489; https://doi.org/10.3390/pharmaceutics14071489 - 18 Jul 2022

Cited by 4 | Viewed by 1513

Abstract

Aloe gel is a medicinal raw material with proven pharmacological activity. The health-promoting properties of other species of Aloe upon topical application prompted us to develop a formulation for the topical application of A. arborescence species. As a result of the gel preparation [...] Read more.

Aloe gel is a medicinal raw material with proven pharmacological activity. The health-promoting properties of other species of Aloe upon topical application prompted us to develop a formulation for the topical application of A. arborescence species. As a result of the gel preparation from the aqueous lyophilized extracts of three-year-old leaves of A. arborescence, no changes in the composition of the content of aloins A and aloenin A were found. The potential to neutralize free radicals was tested using DPPH and CUPRAC techniques, which confirmed the anti-radical activity of the lyophilisate. Screening of the inhibition of enzymes, the hyperactivity of which is associated with adverse changes in the skin of a pro-inflammatory nature, was performed. Importantly, using the PAMPA SKIN model, the possibility of the penetration of selected extract compounds (aloin A and aloenin A) through the skin was proven. Then, two formulations were prepared based on sodium alginate and hydroxypropyl methylcellulose (HPMC) and the hydrogels were characterized (rheological analysis, drug release profiles, permeability, and stability studies). HPMC-based hydrogel was the one with a targeted release of active substances and greater stability. Aloe arborescens hydrogel matrices seem to be a promising treatment strategy for inflammatory surface damage based on “green technology” at the stage of extract preparation and development of the drug form for topical application. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

18 pages, 2633 KiB

Open AccessArticle

Bacterial Cellulose as Drug Delivery System for Optimizing Release of Immune Checkpoint Blocking Antibodies

by Chih Kit Chung, Uwe Beekmann, Dana Kralisch, Katja Bierau, Alan Chan, Ferry Ossendorp and Luis J. Cruz

Pharmaceutics 2022, 14(7), 1351; https://doi.org/10.3390/pharmaceutics14071351 - 25 Jun 2022

Cited by 6 | Viewed by 1734

Abstract

Immune checkpoint blocking therapy is a promising cancer treatment modality, though it has limitations such as systemic toxicity, which can often be traced to uncontrolled antibody spread. Controlling antibody release with delivery systems is, therefore, an attractive approach to reduce systemic antibody spread [...] Read more.

Immune checkpoint blocking therapy is a promising cancer treatment modality, though it has limitations such as systemic toxicity, which can often be traced to uncontrolled antibody spread. Controlling antibody release with delivery systems is, therefore, an attractive approach to reduce systemic antibody spread and potentially mitigate the side effects of checkpoint immunotherapy. Here, bacterial cellulose (BC) was produced and investigated as a delivery system for optimizing checkpoint-blocking antibody delivery. BC was produced in 24-well plates, and afterward, the edges were removed to obtain square-shaped BC samples with a surface of ~49 mm². This customization was necessary to allow smooth in vivo implantation. Scanning electron microscopy revealed the dense cellulose network within BC. Human IgG antibody was included as the model antibody for loading and release studies. IgG antibody solution was injected into the center of BC samples. In vitro, all IgG was released within 24 to 48 h. Cell culture experiments demonstrated that BC neither exerted cytotoxic effects nor induced dendritic cell activation. Antibody binding assays demonstrated that BC does not hamper antibody function. Finally, antibody-loaded BC was implanted in mice, and serum measurements revealed that BC significantly reduced IgG and anti-CTLA-4 spread in mice. BC implantation did not induce side effects in mice. Altogether, BC is a promising and safe delivery system for optimizing the delivery and release of checkpoint-blocking antibodies. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

19 pages, 4549 KiB

Open AccessArticle

Log P Determines Licorice Flavonoids Release Behaviors and Classification from CARBOMER Cross-Linked Hydrogel

by Zhuxian Wang, Yi Hu, Yaqi Xue, Zhaoming Zhu, Yufan Wu, Quanfu Zeng, Yuan Wang, Chunyan Shen, Qun Shen, Cuiping Jiang, Li Liu, Hongxia Zhu and Qiang Liu

Pharmaceutics 2022, 14(7), 1333; https://doi.org/10.3390/pharmaceutics14071333 - 24 Jun 2022

Cited by 7 | Viewed by 1687

Abstract

The dynamic drug release mechanisms from Carbomer 940 (CP) hydrogels have not been systematically explored elsewhere. This study aimed to investigate the quantitative structure−activity relationship of licorice flavonoids (LFs) compounds on their drug release from CP hydrogels based on LFs-CP interactions and drug [...] Read more.

The dynamic drug release mechanisms from Carbomer 940 (CP) hydrogels have not been systematically explored elsewhere. This study aimed to investigate the quantitative structure−activity relationship of licorice flavonoids (LFs) compounds on their drug release from CP hydrogels based on LFs-CP interactions and drug solubility in the release medium. Ten LFs-CP hydrogels were formulated, and their in vitro release study was conducted. The intermolecular forces of LFs-CP systems were characterized by FTIR, molecular docking and molecular dynamic simulation. Ten LFs compounds were classified into I (high-release capability) LFs and II (low-release capability) LFs according to the different negative correlations between drug release percent at 48 h and intermolecular forces of drugs-CP, respectively. Moreover, high-release LFs possessed significantly lower log P and higher drug solubility in the release medium than low-release LFs. All I LFs release behaviors best followed the first-order equation, while II LFs release characteristics best fitted the zero-order equation except for isoliquiritigenin. Log P mainly affect the hydrogel relaxation process for I drugs release and the drug diffusion process for II drugs release. Higher log P values for LFs resulted in higher intermolecular strength for I drugs-CP systems and lower drug solubility in the release medium for II drugs, which hindered drug release. Hydrophobic association forces in drug-CP hydrogel played a more and more dominant role in hindering I LFs release with increasing release time. On the other hand, lower drug solubility in the release medium restricted II LFs release, and the dominant role of drug solubility in the release medium increased in 24 h followed by a significant decline after 36 h. Collectively, log P of LFs served as a bridge to determine LFs compound release behaviors and classification from CP hydrogels, which provided guidelines for reasonable design of LFs hydrogels in pharmaceutical topical formulations. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

19 pages, 2225 KiB

Open AccessArticle

The Release of a Highly Cytotoxic Paullone Bearing a TEMPO Free Radical from the HSA Hydrogel: An EPR Spectroscopic Characterization

by Ana Vesković, Đura Nakarada, Olga Vasiljević, Anatolie Dobrov, Gabriella Spengler, Éva A. Enyedy, Vladimir B. Arion and Ana Popović Bijelić

Pharmaceutics 2022, 14(6), 1174; https://doi.org/10.3390/pharmaceutics14061174 - 30 May 2022

Cited by 2 | Viewed by 2379

Abstract

This study shows the potential of a thermally induced human serum albumin (HSA) hydrogel to serve as a drug depot for sustained release of a highly cytotoxic modified paullone ligand bearing a TEMPO free radical (HL). The binding of HL to [...] Read more.

This study shows the potential of a thermally induced human serum albumin (HSA) hydrogel to serve as a drug depot for sustained release of a highly cytotoxic modified paullone ligand bearing a TEMPO free radical (HL). The binding of HL to HSA was studied by electron paramagnetic resonance (EPR) spectroscopy and imaging. The EPR protocol was also implemented for the study of matrix degradation, and ligand diffusion rate, in two additional spin-labeled hydrogels, containing 5-doxylstearate and 3-carbamoyl-proxyl. The results showed that the hydrogel is an efficient HL reservoir as it retained 60% of the ligand during 11 days of dialysis in physiological saline. Furthermore, upon incubation with Colo 205 human colon adenocarcinoma cells for 3 days, the HL/HSA hydrogel did not exhibit cytotoxic activity, demonstrating that it is also an efficient ligand depot in the presence of living cells. It was observed that the percentage of HL release is independent of its initial concentration in the hydrogel, suggesting that HSA possesses a specific binding site for the ligand, most likely Sudlow site 2, as predicted by molecular docking. The intrinsic property of albumin to bind and transport various substances, including hydrophobic drugs, may be fine-tuned by appropriate physical/chemical hydrogel preparation procedures, providing optimal drug delivery. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Graphical abstract

19 pages, 10410 KiB

Open AccessEditor’s ChoiceArticle

Combined Release of Antiseptic and Antibiotic Drugs from Visible Light Polymerized Biodegradable Nanocomposite Hydrogels for Periodontitis Treatment

by Jozsef Bako, Ferenc Toth, Jozsef Gall, Renato Kovacs, Attila Csík, Istvan Varga, Anton Sculean, Romana Zelko and Csaba Hegedus

Pharmaceutics 2022, 14(5), 957; https://doi.org/10.3390/pharmaceutics14050957 - 28 Apr 2022

Cited by 9 | Viewed by 2477

Abstract

The in situ application of the combination of different types of drugs revolutionized the area of periodontal therapy. The purpose of this study was to develop nanocomposite hydrogel (NCHG) as a pH-sensitive drug delivery system. To achieve local applicability of the NCHG in [...] Read more.

The in situ application of the combination of different types of drugs revolutionized the area of periodontal therapy. The purpose of this study was to develop nanocomposite hydrogel (NCHG) as a pH-sensitive drug delivery system. To achieve local applicability of the NCHG in dental practice, routinely used blue-light photopolymerization was chosen for preparation. The setting time was 60 s, which resulted in stable hydrogel structures. Universal Britton–Robinson buffer solutions were used to investigate the effect of pH in the range 4–12 on the release of drugs that can be used in the periodontal pocket. Metronidazole was released from the NCHGs within 12 h, but chlorhexidine showed a much longer elution time with strong pH dependence, which lasted more than 7 days as it was corroborated by the bactericidal effect. The biocompatibility of the NCHGs was proven by Alamar-blue test and the effectiveness of drug release in the acidic medium was also demonstrated. This fast photo-polymerizable NCHG can help to establish a locally applicable combined drug delivery system which can be loaded with the required amount of medicines and can reduce the side effects of the systemic use of drugs that have to be used in high doses to reach an ideal concentration locally. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Graphical abstract

12 pages, 3426 KiB

Open AccessArticle

Dual Responsive poly(vinyl caprolactam)-Based Nanogels for Tunable Intracellular Doxorubicin Delivery in Cancer Cells

by Kummara Madhusudana Rao, Maduru Suneetha, Dachuru Vinay Kumar, Hyeon Jin Kim, Yong Joo Seok and Sung Soo Han

Pharmaceutics 2022, 14(4), 852; https://doi.org/10.3390/pharmaceutics14040852 - 13 Apr 2022

Cited by 12 | Viewed by 2076

Abstract

In this work, doxorubicin (Dox)-encapsulated poly(vinyl caprolactam) (PVCL)-based three-dimensional nanogel networks were developed and were crosslinked with disulfide linkages. The nanogels degrade rapidly to low molecular weight chains in the presence of the typical intracellular concentration of glutathione. Doxorubicin (Dox) was successfully encapsulated [...] Read more.

In this work, doxorubicin (Dox)-encapsulated poly(vinyl caprolactam) (PVCL)-based three-dimensional nanogel networks were developed and were crosslinked with disulfide linkages. The nanogels degrade rapidly to low molecular weight chains in the presence of the typical intracellular concentration of glutathione. Doxorubicin (Dox) was successfully encapsulated into these nanogels. The nanogels have a high drug loading of 49% and can be tailored to 182 nm to deliver themselves to the targeted cells and release Dox under dual stimuli conditions, such as redox and temperature. By evaluating cell viability in the HepG2 cell line, we observed that Dox-loaded nanogels effectively killed the cancer cell. Fluorescence microscopy results show that the nanogels could easily be internalized with HepG2 cells. The results confirm that the nanogels destabilized in intracellular cytosol via degradation of disulfide bonds in nanogels networks and release of the Dox nearby the nucleus. These carriers could be promising for cancer drug delivery. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

17 pages, 4537 KiB

Open AccessEditor’s ChoiceArticle

Injectable Hydrogel Based on Protein-Polyester Microporous Network as an Implantable Niche for Active Cell Recruitment

by V.H. Giang Phan, Mohanapriya Murugesan, Panchanathan Manivasagan, Thanh Loc Nguyen, Thuy-Hien Phan, Cuong Hung Luu, Duy-Khiet Ho, Yi Li, Jaeyun Kim, Doo Sung Lee and Thavasyappan Thambi

Pharmaceutics 2022, 14(4), 709; https://doi.org/10.3390/pharmaceutics14040709 - 26 Mar 2022

Cited by 11 | Viewed by 3118

Abstract

Despite the potential of hydrogel-based localized cancer therapies, their efficacy can be limited by cancer recurrence. Therefore, it is of great significance to develop a hydrogel system that can provoke robust and durable immune response in the human body. This study has developed [...] Read more.

Despite the potential of hydrogel-based localized cancer therapies, their efficacy can be limited by cancer recurrence. Therefore, it is of great significance to develop a hydrogel system that can provoke robust and durable immune response in the human body. This study has developed an injectable protein-polymer-based porous hydrogel network composed of lysozyme and poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-b-poly(ε-caprolactone-co-lactide (PCLA) (Lys-PCLA) bioconjugate for the active recruitment dendritic cells (DCs). The Lys-PCLA bioconjugates are prepared using thiol-ene reaction between thiolated lysozyme (Lys-SH) and acrylated PCLA (PCLA-Ac). The free-flowing Lys-PCLA bioconjugate sols at low temperature transformed to immovable gel at the physiological condition and exhibited stability upon dilution with buffers. According to the in vitro toxicity test, the Lys-PCLA bioconjugate and PCLA copolymer were non-toxic to RAW 263.7 cells at higher concentrations (1000 µg/mL). In addition, subcutaneous administration of Lys-PCLA bioconjugate sols formed stable hydrogel depot instantly, which suggested the in situ gel forming ability of the bioconjugate. Moreover, the Lys-PCLA bioconjugate hydrogel depot formed at the interface between subcutaneous tissue and dermis layers allowed the active migration and recruitment of DCs. As suggested by these results, the in-situ forming injectable Lys-PCLA bioconjugate hydrogel depot may serve as an implantable immune niche for the recruitment and modification of DCs. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

Review

Jump to: Research

26 pages, 4077 KiB

Open AccessReview

Hydrogel Drug Delivery Systems for Bone Regeneration

by Long Bai, Gang Tao, Maogeng Feng, Yuping Xie, Shuyu Cai, Shuanglin Peng and Jingang Xiao

Pharmaceutics 2023, 15(5), 1334; https://doi.org/10.3390/pharmaceutics15051334 - 25 Apr 2023

Cited by 7 | Viewed by 2361

Abstract

With the in-depth understanding of bone regeneration mechanisms and the development of bone tissue engineering, a variety of scaffold carrier materials with desirable physicochemical properties and biological functions have recently emerged in the field of bone regeneration. Hydrogels are being increasingly used in [...] Read more.

With the in-depth understanding of bone regeneration mechanisms and the development of bone tissue engineering, a variety of scaffold carrier materials with desirable physicochemical properties and biological functions have recently emerged in the field of bone regeneration. Hydrogels are being increasingly used in the field of bone regeneration and tissue engineering because of their biocompatibility, unique swelling properties, and relative ease of fabrication. Hydrogel drug delivery systems comprise cells, cytokines, an extracellular matrix, and small molecule nucleotides, which have different properties depending on their chemical or physical cross-linking. Additionally, hydrogels can be designed for different types of drug delivery for specific applications. In this paper, we summarize recent research in the field of bone regeneration using hydrogels as delivery carriers, detail the application of hydrogels in bone defect diseases and their mechanisms, and discuss future research directions of hydrogel drug delivery systems in bone tissue engineering. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

23 pages, 2024 KiB

Open AccessReview

Nano-Based Drug Delivery Systems for Periodontal Tissue Regeneration

by Huanhuan Chen, Yunfan Zhang, Tingting Yu, Guangying Song, Tianmin Xu, Tianyi Xin, Yifan Lin and Bing Han

Pharmaceutics 2022, 14(10), 2250; https://doi.org/10.3390/pharmaceutics14102250 - 21 Oct 2022

Cited by 9 | Viewed by 2296

Abstract

Periodontitis is a dysbiotic biofilm-induced and host-mediated inflammatory disease of tooth supporting tissues that leads to progressive destruction of periodontal ligament and alveolar bone, thereby resulting in gingival recession, deep periodontal pockets, tooth mobility and exfoliation, and aesthetically and functionally compromised dentition. Due [...] Read more.

Periodontitis is a dysbiotic biofilm-induced and host-mediated inflammatory disease of tooth supporting tissues that leads to progressive destruction of periodontal ligament and alveolar bone, thereby resulting in gingival recession, deep periodontal pockets, tooth mobility and exfoliation, and aesthetically and functionally compromised dentition. Due to the improved biopharmaceutical and pharmacokinetic properties and targeted and controlled drug release, nano-based drug delivery systems have emerged as a promising strategy for the treatment of periodontal defects, allowing for increased efficacy and safety in controlling local inflammation, establishing a regenerative microenvironment, and regaining bone and attachments. This review provides an overview of nano-based drug delivery systems and illustrates their practical applications, future prospects, and limitations in the field of periodontal tissue regeneration. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

31 pages, 3088 KiB

Open AccessReview

Drug Delivery Strategies and Biomedical Significance of Hydrogels: Translational Considerations

by Neha Raina, Rakesh Pahwa, Jaydeep Bhattacharya, Alok K. Paul, Veeranoot Nissapatorn, Maria de Lourdes Pereira, Sonia M. R. Oliveira, Karma G. Dolma, Mohammed Rahmatullah, Polrat Wilairatana and Madhu Gupta

Pharmaceutics 2022, 14(3), 574; https://doi.org/10.3390/pharmaceutics14030574 - 05 Mar 2022

Cited by 21 | Viewed by 4385

Abstract

Hydrogels are a promising and attractive option as polymeric gel networks, which have immensely fascinated researchers across the globe because of their outstanding characteristics such as elevated swellability, the permeability of oxygen at a high rate, good biocompatibility, easy loading, and drug release. [...] Read more.

Hydrogels are a promising and attractive option as polymeric gel networks, which have immensely fascinated researchers across the globe because of their outstanding characteristics such as elevated swellability, the permeability of oxygen at a high rate, good biocompatibility, easy loading, and drug release. Hydrogels have been extensively used for several purposes in the biomedical sector using versatile polymers of synthetic and natural origin. This review focuses on functional polymeric materials for the fabrication of hydrogels, evaluation of different parameters of biocompatibility and stability, and their application as carriers for drugs delivery, tissue engineering and other therapeutic purposes. The outcome of various studies on the use of hydrogels in different segments and how they have been appropriately altered in numerous ways to attain the desired targeted delivery of therapeutic agents is summarized. Patents and clinical trials conducted on hydrogel-based products, along with scale-up translation, are also mentioned in detail. Finally, the potential of the hydrogel in the biomedical sector is discussed, along with its further possibilities for improvement for the development of sophisticated smart hydrogels with pivotal biomedical functions. Full article

(This article belongs to the Special Issue Hydrogels in Drug Delivery: Progress and Challenges)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Hydrogels in Drug Delivery: Progress and Challenges

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (16 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI