In this article, silver and magnetite nanofillers were synthesized in modified κ-carrageenan hydrogels using the in situ method. The effect of metallic nanoparticles in gastro-intestinal tract (GIT) release of a model drug (methylene blue) has been investigated. The effect of nanoparticles loading and genipin cross-linking on GIT release of nanocomposite is also studied to finally provide the most suitable drug carrier system. In vitro release studies revealed that using metallic nanocomposites hydrogels in GIT studies can improve the drug release in intestine and minimize it in the stomach. It was found that cross-linking and nanofiller loading can significantly improve the targeted release. Therefore, applying metallic nanoparticles seems to be a promising strategy to develop GIT controlled drug delivery.
Natural biopolymers have attracted considerable interest for the development of delivery systems for protein drugs owing to their biocompatibility, non-toxicity, renewability and mild processing conditions. This paper offers an overview of the current status and future perspectives of particle designs using biopolymers for the stabilization and controlled-delivery of a model protein drug--insulin. We first describe the design criteria for polymeric encapsulation and subsequently classify the basic principles of particle fabrication as well as the existing particle designs for oral insulin encapsulation. The performances of these existing particle designs in terms of insulin stability and in vitro release behavior in acidic and alkaline media, as well as their in vivo performance are compared and reviewed. This review forms the basis for future works on the optimization of particle design and material formulation for the development of an improved oral delivery system for protein drugs.
A poly(vinyl alcohol) (PVA) hydrogel composite scaffold containing N,O-carboxymethylated chitosan (NOCC) was tested to assess its potential as a scaffold for cartilage tissue engineering in a weight-bearing environment. The mechanical properties under unconfined compression for different hydration periods were investigated. The effect of supplementing PVA with NOCC (20wt.% PVA:5vol.% NOCC) produced a porosity of 43.3% and this was compared against a non-porous PVA hydrogel (20g PVA: 100ml of water, control). Under non-hydrated conditions, the porous PVA-NOCC hydrogel behaved in a similar way to the control non-porous PVA hydrogel, with similar non-linear stress-strain response under unconfined compression (0-30% strain). After 7days' hydration, the porous hydrogel demonstrated a reduced stiffness (0.002kPa, at 25% strain), resulting in a more linear stiffness relationship over a range of 0-30% strain. Poisson's ratio for the hydrated non-porous and porous hydrogels ranged between 0.73 and 1.18, and 0.76 and 1.33, respectively, suggesting a greater fluid flow when loaded. The stress relaxation function for the porous hydrogel was affected by the hydration period (from 0 to 600s); however the percentage stress relaxation regained by about 95%, after 1200s for all hydration periods assessed. No significant differences were found between the different hydration periods between the porous hydrogels and control. The calculated aggregate modulus, H(A), for the porous hydrogel reduced drastically from 10.99kPa in its non-hydrated state to about 0.001kPa after 7days' hydration, with the calculated shear modulus reducing from 30.92 to 0.14kPa, respectively. The porous PVA-NOCC hydrogel conformed to a biphasic, viscoelastic model, which has the desired properties required for any scaffold in cartilage tissue engineering.
The gastroretentive dosage form of famotidine was modified using tamarind seed powders to prolong the gastric retention time. Tamarind seeds were used in two different forms having different swelling and gelling properties: with husk (TSP) or without husk (TKP). TKP (TKP1 to TKP 6) and TSP (TSP1 to TSP 6) series were prepared using tamarind powder:xanthan in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4, 0:5, respectively. The matrix tablets were prepared by the wet granulation method and evaluated for pharmacopoeial requirements. TKP2 was the optimum formulation as it had a short floating lag time (FLT<30 s) and more than 98.5% drug release in 12 h. The dissolution data were fitted to popular mathematical models to assess the mechanism of drug release, and the optimum formulation showed a predominant first order release and diffusion mechanism. It was concluded that the TKP2 prepared using tamarind kernel powder:xanthan (4:1) was the optimum formulation with shortest floating lag time and more than 90% release in the determined period of time.
Silver (Ag) coated bioactive glass particles (Ag-BG) were formulated and compared to uncoated controls (BG) in relation to glass characterization, solubility and microbiology. X-ray diffraction (XRD) confirmed a crystalline AgNP surface coating while ion release studies determined low Ag release (<2 mg/L). Cell culture studies presented increased cell viability (127 and 102%) with lower liquid extract (50 and 100 ml/ml) concentrations. Antibacterial testing of Ag-BG in E. coli, S. epidermidis and S. aureus significantly reduced bacterial cell viability by 60-90%. Composites of Ag-BG/CMC-Dex Hydrogels were formulated and characterized. Agar diffusion testing was conducted where Ag-BG/hydrogel composites produced the largest inhibition zones of 7 mm (E. coli), 5 mm (S. aureus) and 4 mm (S. epidermidis).
Recently noted that the methylene blue cause severe central nervous system toxicity. It is essential to optimize the methylene blue from aqueous environment. In this study, a comparison of an optimization of methylene blue was investigated by using modified Ca(2+) and Zn(2+) bio-polymer hydrogel beads. A batch mode study was conducted using various parameters like time, dye concentration, bio-polymer dose, pH and process temperature. The isotherms, kinetics, diffusion and thermodynamic studies were performed for feasibility of the optimization process. Freundlich and Langmuir isotherm equations were used for the prediction of isotherm parameters and correlated with dimensionless separation factor (RL). Pseudo-first order and pseudo-second order Lagegren's kinetic equations were used for the correlation of kinetic parameters. Intraparticle diffusion model was employed for diffusion of the optimization process. The Fourier Transform Infrared Spectroscopy (FTIR) shows different absorbent peaks of Ca(2+) and Zn(2+) beads and the morphology of the bio-polymer material analyzed with Scanning Electron Microscope (SEM). The TG & DTA studies show that good thermal stability with less humidity without production of any non-degraded products.
A new approach to design multifunctional chitosan based nanohydrogel with enhanced glucose sensitivity, stability, drug loading and release profile are reported. Two approaches were followed for functionalization of chitosan based nanohydrogel with 3-APBA via EDC and 3-APTES. The effective functionalization, structure and morphology of Chitosan based IPN respectively were confirmed by FTIR, SEM and AFM. At physiological conditions, the glucose-induced volume phase transition and release profile of the model drug Alizarin Red with 1,2-diol structure (comparative to insulin as a drug as well as a dye for bio separation) were studied at various glucose concentrations, pH and ionic strengths. The results suggested a new concept for diabetes treatment and diols sensitivity in view of their potential hi-tech applications in self-regulated on-off response to the treatment (drug delivery and bio separation concurrently).
This study investigates the preliminary efficacy of drug encapsulation in chitosan hydrogels by cathodic electrodeposition for the encapsulation of the aromatic dye methyl orange to enhance drug delivery in biological systems. Chitosan, a biocompatible and transparent polymer, is known for its ability to effectively encapsulate and transport therapeutic agents, which is critical for sustained and targeted drug release. Methyl orange was selected as a model drug to study the effects of deposition and immersion times on encapsulation efficiency. The effects of deposition and immersion times on encapsulation efficiency were analyzed by synthesizing multilayer hydrogels via electrochemical oxidation. Characterization techniques, including UV-visible spectroscopy, FTIR, and NMR, were employed; FTIR indicated an effective absorption of 4.34 % for Td50Ti60, while UV-Vis showed 46.41 % at Td60Ti50. NMR analysis revealed effective concentrations of 0.47 mM for Td70Ti60 and 0.38 mM for Td60Ti50, indicating that longer immersion times enhance absorption. These findings provide a foundation for further studies aimed at optimizing drug delivery strategies and improving the therapeutic efficacy of encapsulated agents in biological applications.
A new fusidic acid-loaded hydrogel film was prepared via the solvent casting technique using alginate and Aloe vera. The hydrogel films were optimized using different ratios of sodium alginate, Aloe vera, and glycerin. The films containing 10% glycerin (w/w of alginate) exhibited the best appearance. Incorporating Aloe vera influenced the thickness, swelling behavior, water vapor permeability, and drug release profile of the hydrogel films. Higher Aloe vera content resulted in thicker films (up to a certain ratio), increased swelling, reduced water vapor permeability, and a prolonged drug release of up to 93% over 12 h. Fourier-transform infrared spectroscopy (FTIR) analysis confirmed the presence of key functional groups and the interaction between the hydrogel components. The study suggests that the combination of sodium alginate, Aloe vera, and glycerin can improve the mechanical properties and drug release profiles of hydrogel films, making them a promising option for enhanced topical drug delivery and wound healing applications.
The present study aims to formulate a stimuli-responsive in situ hydrogel system to codeliver acacia honey and glycyrrhizic acid for topical application that will aid in absorbing wound exudates, control microbial infestation, and produce angiogenic and antioxidant effects to accelerate wound healing. Therefore, both the natural active constituents were incorporated within an in situ hydrogel composed of poloxamer and hydroxypropyl methylcellulose (HPMC), where the concentrations of the polymers were optimized using Design-Expert software considering optimum values of the dependent variables, gelation temperature (34-37 °C), gelation time (<10 min), and the viscosity (2000-3500 cPs). The optimized formulation showed improved physicochemical properties such as mucoadhesiveness, porosity, swelling, and spreadability, which makes it suitable for wound application. Additionally, the in situ hydrogel exhibited potent in vitro and ex vivo antioxidant effects, in vitro antimicrobial activities, and ex ovo angiogenic effects. Furthermore, the optimized formulation was found to be nontoxic while tested in the HaCaT cell line and acute dermal irritation and corrosion study. The findings of the in vivo wound-healing studies in experimental animal models showed complete wound closure within 15 days of treatment and accelerated development of the extracellular matrix. In addition, the antioxidant, antimicrobial, angiogenic, and wound-healing properties of acacia honey and glycyrrhizic acid coloaded in situ hydrogel were also found to be promising when compared to the standard treatments. Overall, it can be concluded that the optimized stimuli-responsive in situ hydrogel containing two natural compounds could be an alternative to existing topical formulations for acute wounds.
Effective wound healing requires biocompatible and functional wound dressings. This study explores the synergistic potential of gellan gum (GG), known for its exceptional gel-forming abilities, and acacia stingless bee honey (SBH), for its potent antioxidant properties, in developing advanced wound care solutions. GG hydrogel films incorporated with varying concentrations of SBH (v/v) at 10 % (GGSBH10), 15 % (GGSBH15), and 20 % (GGSBH20) were characterized. The incorporation of SBH into the GG matrix resulted in distinctive spectral peaks of ATR-FTIR associated with SBH, particularly evident in GGSBH20. Among the formulations, GGSBH20 demonstrated an impressive water vapor transmission rate of 1149 ± 11 g m-2 d-1 and a swelling ratio of 169 ± 7 %. Disk diffusion revealed that E. coli was susceptible to GGSBH. Cytotoxicity assessments (MTT and scratch assays) on 3 T3-L1 cells confirmed the biocompatibility of GGSBH, which showed no cytotoxic effects up to 72 h of incubation, and improved cell viability. Notably, GGSBH20 displayed the highest wound closure rate, significantly enhancing cell migration and proliferation. Overall, our findings underscore the promising healing properties of GG hydrogel films when enriched with acacia SBH, highlighting their potential as effective and innovative wound dressing materials.
There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug delivery carriers.
Novel pH sensitive N-succinyl chitosan-g-poly (acrylic acid) hydrogels were synthesized through free radical mechanism. Rheometer was used to observe the mechanical strength of the hydrogels. In vitro degradation was conducted in SIF (pH 7.4). The effect of concentration of monomers, initiator, and crosslinking agent and pH and ionic strength of NaCl, CaCl2, and AlCl3 on swelling of the hydrogels was observed. The results showed that equilibrium swelling ratio was highly influenced by concentration of monomers, initiator, and crosslinking agent concentration, and pH and salt solutions of NaCl, CaCl2, and AlCl3. The swelling kinetics revealed that swelling followed non-Fickian anomalous transport. Furthermore, theophylline loading (DL %) and encapsulation efficiency (EE %) of the hydrogels was in the range of 15.5 ± 0.15-22.8 ± 0.06% and 62 ± 0.15-91 ± 0.26%, respectively. The release of theophylline in physiological mediums was strongly influenced by the pH. The theophylline release was in the range of 51 ± 0.20-92 ± 0.12% in SIF and 7.4 ± 0.02-14.9 ± 0.03% in SGF (pH 1.2), respectively. The release data fitted well to Korsmeyer-Peppas model. The chemical activity of the theophylline suggested that drug maintained its chemical activity after release in vitro. The results suggest that synthesized hydrogels are excellent drug carriers.
Natural biopolymers have many attractive medical applications; however, complications due to fibrosis caused a reduction in diffusion and dispersal of nutrients and waste products. Consequently, severe immunocompatibility problems and poor mechanical and degradation properties in synthetic polymers ensue. Hence, the present study investigates a novel hydrogel material synthesized from caprolactone, ethylene glycol, ethylenediamine, polyethylene glycol, ammonium persulfate, and tetramethylethylenediamine via chemo-enzymatic route. Spectroscopic analyses indicated the formation of polyurea and polyhydroxyurethane as the primary building block of the hydrogel starting material. Biocompatibility studies showed positive observation in biosafety test using direct contact cytotoxicity assay in addition to active cellular growth on the hydrogel scaffold based on fluorescence observation. The synthesized hydrogel also exhibited (self)fluorescence properties under specific wavelength excitation. Hence, synthesized hydrogel could be a potential candidate for medical imaging as well as tissue engineering applications as a tissue expander, coating material, biosensor, and drug delivery system.
Polysaccharides are excellent candidates for drug delivery applications as they are available in abundance from natural sources. Polysaccharides such as starch, cellulose, lignin, chitosan, alginate, and tragacanth gum are used to make hydrogels beads. Hydrogels beads are three-dimensional, cross-linked networks of hydrophilic polymers formed in spherical shape and sized in the range of 0.5-1.0 mm of diameter. Beads are formed by various cross-linking methods such as chemical and irradiation methods. Natural polymer-based hydrogels are biocompatible and biodegradable and have inherently low immunogenicity, which makes them suitable for physiological drug delivery approaches. The cross-linked polysaccharide-based hydrogels are environment-sensitive polymers that can potentially be used for the development of "smart" delivery systems, which are capable of control release of the encapsulated drug at a targeted colon site. This topic focuses on various aspects of fabricating and optimizing the cross-linking of polysaccharides, either by a single polysaccharide or mixtures and also natural-synthetic hybrids to produce polymer-based hydrogel vehicles for colon-targeted drug delivery.
The development of hydrogel films as wound healing dressings is of a great interest owing to their biological tissue-like nature. Polyvinyl alcohol/polyethylene glycol (PVA/PEG) hydrogels loaded with asiaticoside, a standardized rich fraction of Centella asiatica, were successfully developed using the freeze-thaw method. Response surface methodology with Box-Behnken experimental design was employed to optimize the hydrogels. The hydrogels were characterized and optimized by gel fraction, swelling behavior, water vapor transmission rate and mechanical strength. The formulation with 8% PVA, 5% PEG 400 and five consecutive freeze-thaw cycles was selected as the optimized formulation and was further characterized by its drug release, rheological study, morphology, cytotoxicity and microbial studies. The optimized formulation showed more than 90% drug release at 12 hours. The rheological properties exhibited that the formulation has viscoelastic behavior and remains stable upon storage. Cell culture studies confirmed the biocompatible nature of the optimized hydrogel formulation. In the microbial limit tests, the optimized hydrogel showed no microbial growth. The developed optimized PVA/PEG hydrogel using freeze-thaw method was swellable, elastic, safe, and it can be considered as a promising new wound dressing formulation.
Research was aimed on microemulsion-based hydrogel for voriconazole. Oleic acid and isopropyl myristate as lipid phases; tween 20: tween 80 as surfactants and PEG600 as cosurfactant were selected to formulate voriconazole microemulsions. The promising microemulsions in terms of zeta potential, pH, viscosity, and drug release were selected and developed into hydrogels using carbopol 934. Resulting microemulsion-based hydrogel (MBH) of voriconazole were evaluated for in vitro diffusion and ex vivo permeation. Antifungal potentials of MBH were assessed against selected fungal strains. Optimal MBH formulations, O6 and O8 had displayed their antifungal potentials with enlarged zone of inhibition against selected fungal strains.
The present research is based on the fabrication preparation of CS/PVA/GG blended hydrogel with nontoxic tetra orthosilicate (TEOS) for sustained paracetamol release. Different TEOS percentages were used because of their nontoxic behavior to study newly designed hydrogels' crosslinking and physicochemical properties. These hydrogels were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and wetting to determine the functional, surface morphology, hydrophilic, or hydrophobic properties. The swelling analysis in different media, degradation in PBS, and drug release kinetics were conducted to observe their response against corresponding media. The FTIR analysis confirmed the components added and crosslinking between them, and surface morphology confirmed different surface and wetting behavior due to different crosslinking. In various solvents, including water, buffer, and electrolyte solutions, the swelling behaviour of hydrogel was investigated and observed that TEOS amount caused less hydrogel swelling. In acidic pH, hydrogels swell the most, while they swell the least at pH 7 or higher. These hydrogels are pH-sensitive and appropriate for controlled drug release. These hydrogels demonstrated that, as the ionic concentration was increased, swelling decreased due to decreased osmotic pressure in various electrolyte solutions. The antimicrobial analysis revealed that these hydrogels are highly antibacterial against Gram-positive (Staphylococcus aureus and Bacillus cereus) and Gram negative (Pseudomonas aeruginosa and Escherichia coli) bacterial strains. The drug release mechanism was 98% in phosphate buffer saline (PBS) media at pH 7.4 in 140 min. To analyze drug release behaviour, the drug release kinetics was assessed against different mathematical models (such as zero and first order, Higuchi, Baker-Lonsdale, Hixson, and Peppas). It was found that hydrogel (CPG2) follows the Peppas model with the highest value of regression (R2 = 0.98509). Hence, from the results, these hydrogels could be a potential biomaterial for wound dressing in biomedical applications.
In this study, MgO nanoparticles are applied to control the initial burst release by modification of matrix structure, thereby affecting the release mechanism. The effects of MgO nanofiller loading on the in vitro release of a model drug are investigated. Surface topography and release kinetics of hydrogel nanocomposites are also studied in order to have better insight into the release mechanism. It was found that the incorporation of MgO nanofillers can significantly decrease the initial burst release. The effect of genipin (GN) on burst release was also compared with MgO nanoparticles, and it was found that the impact of MgO on burst release reduction is more obvious than GN; however, GN cross-linking caused greater final release compared to blanks and nanocomposites. To confirm the capability of nanocomposite hydrogels to reduce burst release, the release of β-carotene in Simulated Gastric Fluid and Simulated Intestinal Fluid was also carried out. Thus, the application of MgO nanoparticles seems to be a promising strategy to control burst release.
The carboxymethyl sago pulp (CMSP) with a degree of substitution of 0.4% was synthesized from sago waste. The CMSP beads with an average diameter of 3.1-4.8 mm were formed by aluminium chloride gelation as well as further cross-linked by irradiation. To evaluate colon targeted release, a model drug, 5-aminosalicylic acid (5-ASA) was encapsulated in CMSP beads. Fourier-transform infrared spectroscopy and X-ray diffraction studies indicated intact and amorphous nature of entrapped drug. A pH dependent drug release was observed, and about 90% of the drug was released only at pH 7.4 over 9 h. Irradiated beads were resisted the drug release in an acidic environment at a higher extent than non-irradiated beads. The drug release from 6% (w/w) of 5-ASA loaded bead followed zero order, whereas, 15 and 22% loaded beads followed first order. The release exponent n value suggests non-fickian transport of 5-ASA from the beads.