Smart controlled release of acarbose from glucose-sensitive hydrogels comprising covalently modified carboxylated pullulan and concanavalin A

A hydrogel comprising covalently modified carboxylated pullulan and concanavalin A (CPUL-ConA) was prepared with glucose-sensitivity in a simulated small intestinal fluid containing glucose. The acarbose-encapsulated CPUL-ConA (Acar/CPUL-ConA) hydrogel, with an acarbose encapsulation ratio of 0.63, was prepared by immersing the dried CPUL-ConA hydrogel in an acarbose/PBS (pH 7.2) solution. In the simulated gastric fluid, less than 20% acarbose was released from the Acar/CPUL-ConA hydrogel, which could be beneficial to protecting the stomach. In contrast, more than 80% acarbose was smartly controlled released from the Acar/CPUL-ConA hydrogel in the simulated small intestine fluid containing glucose. Scanning electron microscopy provided further evidence of the smart release of acarbose from the Acar/CPUL-ConA hydrogel in simulated gastrointestinal fluids, which is advantageous to inhibiting α-glucosidase activity and subsequently reducing the postprandial blood glucose levels, as well as helpful for reducing the gastrointestinal dysfunction of acarbose. Rheological analysis indicated that the Acar/CPUL-ConA hydrogel showed characteristics of chemical crosslinked hydrogels. There was no obvious shear thinning behavior, suggesting that the Acar/CPUL-ConA hydrogel could be stable under gastric and intestinal peristalsis. Therefore, the Acar/CPUL-ConA hydrogel is anticipated to improve the therapeutic efficacy of postprandial hyperglycemia and type 2 diabetes.     

Lanolin‐based organogels as a matrix for topical drug delivery

The current study deals with the development of lanolin‐based emulsion gels by hot emulsification method. Bright‐field, phase contrast, and fluorescent micrographs of the gels have shown the uniform distribution of circular water droplets in the formulations. Coalescence of water droplets was observed in gels containing higher proportion of water. Fourier transform infrared spectrophotometric studies indicated absence of Ln‐drug chemical interactions. X‐ray diffraction studies suggested an increase in amorphousness of the gels with the incorporation of water into the gel structure. The salicylic acid (SA), model drug, release from the gels was found to follow Higuchi kinetics. Krossmeyer–Peppas model fitting indicated non‐Fickian release of the drug. As the water content of the gels increased, there was a corresponding increase in the rate of release of the drug. The gels showed non‐Newtonian and thixotropic flow behavior. The gel to sol transition and melting temperatures of the gels were identified by differential scanning calorimetric (DSC) thermal analysis and falling ball method. DSC thermograms indicated an increase in thermal stability with the increase of water content in the gels. The gels showed sufficient spreadability and biocompatibility characteristics to be used as topical formulations. SA loaded gels showed good antimicrobial efficacy against Bacillus subtilis, a Gram‐positive bacterium. Based on the preliminary studies, the developed gels may be regarded as carriers in topical drug delivery. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

β‐cyclodextrin‐conjugated hyaluronan hydrogel as a potential drug sustained delivery carrier for wound healing

In order to develop a potential drug sustained delivery carrier suitable for wound healing, a series of β‐cyclodextrin conjugated hyaluronan hydrogels (β‐CD‐HA) with adjustable crosslink densities were synthesized and characterized, meanwhile the delivery kinetics and mechanism of diclofenac as a model anti‐inflammatory drug from these hydrogels were investigated. By controlling the feeding molar ratio of β‐CD/HA, a β‐CD substitution degree of 4.65% was obtained by ¹H‐NMR analysis. The incorporation of β‐CD modification had little effect on the internal porous structure, water swelling ratio, and rheological property of HA hydrogel, which however were influenced by the crosslink density. Although the crosslink density had an influence on the drug loading and release profile by altering the water swelling property, the interaction between β‐CD and drug was the primary factor for the high loading capacity and long‐term sustained delivery of diclofenac. The semiempirical equation fit showed that the release of diclofenac from HA‐based hydrogels followed a pseudo‐Fickian diffusion mechanism. By the aid of β‐CD and controlled crosslink density, a β‐CD‐HA hydrogel with a diclofenac sustained delivery period of over 28 days and desirable physicochemical properties was achieved, which will be a promising drug sustained delivery carrier for wound healing. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43072.     

Stimuli-responsive hybrid microgels for controlled drug delivery: Sorafenib as a model drug

Microgels (MGs) are synthetic colloidal hydrogel particles made of three dimensional polymer networks. Their chemical composition is crucial for their use as intelligent drug release systems operated by temperature control. Herein, several MGs using N-isopropylacrylamide (Nipam)/N-isopropylmethacrylamide (Nipmam), chitosan and acrylic/methacrylic acid have been synthesized by free radical polymerization reactions (NC MGs) and the effects of surfactants and different reaction times on size and swelling properties have been investigated. MGs have been identified and characterized by dynamic light scattering and atomic force microscopy, and finally used to optimize the encapsulation protocol of the hydrophobic drug sorafenib. The drug delivery system here described has encapsulation efficiency of 40% and releases 10% of the entrapped drug over about 16 h after the temperature is raised above the volume phase transition temperature. Data suggest that MGs with optimized composition may act as properly instructed entities able to trap and release biomolecules following external stimuli.     

Castor oil and sorbitan monopalmitate based organogel as a probable matrix for controlled drug delivery

The study has been designed to develop and evaluate the in vitro sustained‐release capability of sorbitan monopalmitate (SMP) and castor oil (CO) based organogels. Organogels were prepared by heating the mixture of SMP‐CO at 60°C either with or without using distilled water (DW). The heated mixture was subsequently cooled to room‐temperature to allow the formation of a gelled structure. Characterization of organogels was carried out by microscopy (light, fluorescent, electron, and atomic force), Fourier transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), differential scanning calorimetry (DSC), rheological study, pH, impedance spectroscopy, hemocompatibility, and antimicrobial studies. The properties and stability of the gels was dependent on the composition of the organogels. FTIR studies indicated the presence of strong intramolecular/intermolecular hydrogen bonding amongst the gel components. XRD studies suggested amorphous behavior of the gels. The gels showed a shear thinning behavior. Metronidazole (MZ) loaded gels showed good antimicrobial property to be used as an antimicrobial formulation. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 1503–1515, 2013     

Ethyl methacrylate grafted on two starches as polymeric matrices for drug delivery

The use of copolymers grafted on starch for controlled‐release technology is an interesting proposal, since a modification of a natural polymer is more suitable than synthetic polymers because of its biocompatibility and biodegradability. The aim of this paper is to synthesize acrylic polymers grafted on carbohydrates to investigate the release kinetic of different solubility drugs from polymeric matrix systems and to observe the effect of grafted copolymers and drug solubility on the release mechanism. Copolymer variables such as carbohydrate content, stereoregularity of grafted chains, particle size, morphology, sensitivity to hydration, and rheological properties are discussed. Tablets were prepared by direct compression of the graft copolymer and drug. The drugs' release in vitro kinetics was studied by dissolution testing. Drug release from tablets depends on polymer matrix, polymer content, drug, and pH. An increase in drug solubility results in an increase in the rate of dissolution, as in the case of a poor hydrophilic matrix. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 523–536, 2005     

Dual stimuli responsive glycidyl methacrylate chitosan‐quaternary ammonium hybrid hydrogel and its bovine serum albumin release

A new family of cationic hybrid hydrogels from two new positively charged aqueous soluble precursors, glycidyl methacrylate‐chitosan (GMA‐chitosan), and 2‐(acryloyloxy) ethyl trimethylammonium (AETA), was developed via a simple photocrosslinking fabrication method. These hybrid hydrogels have pendant quaternary ammonium functional groups on the AETA segments. The chemical composition of GMA‐chitosan/AETA hybrid hydrogels were characterized by Fourier transform infrared spectroscopy and their mechanical, swelling, and morphological properties were examined as a function of the composition of the hybrids as well as the effect of pH and ionic strength of the surrounding medium. GMA‐chitosan/AETA hybrid hydrogels show a porous network structure with average pore diameter 20–50 μm. The compression moduli of these hybrid hydrogels ranged from 27.24 to 28.94 kPa, which are significantly higher than a pure GMA‐chitosan (17.64 kPa). GMA‐chitosan/AETA hybrid hydrogel shows pH/ionic strength responsive swelling behavior because of the presence of the positive charge pendant groups. These hybrid hydrogels showed a sustained BSA protein release and a significantly lower initial burst release than a pure GMA‐chitosan hydrogel. The two aqueous soluble precursors and the cationic charge characteristics of the resulting GMA‐chitosan/AETA hybrid hydrogels may suggest that this new family of biomaterials may have promising applications as the pH responsive protein drug delivery vehicles. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 130: 3736–3745, 2013     

Rheological properties and drug release characteristics of pH‐responsive hydrogels

Rheological properties, blend compatibility, and gel‐forming capacity of carbopol 940 (CP‐940), sodium alginate (NaAlg), and guar gum (GG) have been studied. These matrices have been used in delivery of timolol maleate for ophthalmic applications. Aqueous solutions of CP‐940, NaAlg, and GG in concentrations between 0.1 and 1% (wt/vol) and their blends have been prepared. In situ gel forming polymeric solutions have shown an increase in viscosity upon exposure to specific pH, ions, and temperature of the eyeball. Blend miscibility was studied by calculating polymer–polymer interaction parameters using viscosity data. Rheological properties viz., torque, viscosity, shear stress, and shear rate were obtained using a Brookfield rheometer. Viscosities of polymer solutions were obtained by a Schott Gerate viscometer. Rheological data were analyzed using Bingham, Casson Standard, and Casson Chocolate equations. The hydrogels were subjected to ex vivo release studies on timolol maleate through the excised bovine cornea using a modified Franz diffusion cell. Results were compared with the conventional drug solution. The release could be extended when the drug is incorporated into hydrogel‐forming solution. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2057–2064, 2004     

Thermal,electrical, and mechanical properties of tween 80/span 80–based organogels and its application in iontophoretic drug delivery

The present study describes the preparation and characterization of the Tween 80/Span 80 and sunflower oil–based organogels. Organogels were characterized using microscopy, X‐ray diffraction, thermal, mechanical, and electrical techniques. The properties were found to be dependent on the proportion of the water : surfactant mixture. The in vitro drug release studies were performed under electrical potential. The drug release in the presence of electrical current was compared with the passive drug release. The drug release from the organogels followed the zero‐order kinetics suggesting diffusion mediated release. The preliminary results suggested that the organogels may be used as drug carriers in iontophoretic drug delivery. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41419.     

Preparation and characterization of pH responsive poly(methacrylic acid‐acrylamide‐N‐hydroxyethyl acrylamide) hydrogels for drug delivery systems

In this study, pH responsive polymers composed of methacrylic acid, acrylamide, and N‐hydroxyethyl acrylamide were synthesized by free radical polymerization technique. The characterization was done with Fourier transform infrared spectroscopy and scanning electron microscopy. The swelling and drug release behavior of the hydrogels was determined as a function of time at 37°C in pH 2.1 and 7.4. The swelling and drug release studies showed that increased methacrylic acid amount caused a higher increase in swelling and drug release values at pH 7.4 than those at pH 2.1. In addition, the drug release data were applied to kinetic models such as zero order, first order, and Higuchi equations, and it fit well in the Higuchi model of the hydrogel. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43226.     

Design and evaluation of a lyophilized liposomal gel of an antiviral drug for intravaginal delivery

Liposomes of antiviral drug(acyclovir) prepared by rotary evaporation method were incorporated into two bioadhesive polymers, carbopol and HPMC and freeze dried to obtain a unit dosage form. The liposomes, liposomal gels and freeze dried rods were evaluated for various parameters. TEM analysis showed the formation of unilamellar liposomes with a mean diameter ranging from 0.9 μm to 1.2 μm. As the cholesterol content increases from 0.5% to 2%w/w, the entrapment efficiency and vesicle size increased. Carbopol gels exhibited higher viscosity, spreadability, mucoadhesiveness than HPMC gels. The redipsersion of freeze dried forms in SVF was found to be slow and its ex‐vivo retention time was found to be 12 hrs while acyclovir gel retained only for 8.25 hrs. The tablet and gel released 96.93±0.15% acyclovir within 6 hrs and 92.31±0.31% by 8 hrs respectively while freeze dried forms could sustain the release upto 12 hrs. From the stability studies the optimum storage condition was found to be 4‐8°C. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39804.     

Exploring poly(vinyl alcohol) hydrogels containing drug–cyclodextrin complexes as controlled drug delivery systems

Poly(vinyl alcohol) (PVA) hydrogels containing drug–β‐cyclodextrin inclusion complexes (ICs) were synthesized with glutaraldehyde (GA) as a crosslinker. The role of cyclodextrin (CD), the effect of the nature of drug, and the degree of crosslinking on the drug‐release process were investigated. The probable mechanism of drug release was also explored. Controlled release of the drug was achieved from the hydrogels containing the ICs. The nature of the drug, in terms of its binding efficacy with CD, played an important role. The effect of the degree of crosslinking on the release pattern was strikingly different from that in the hydrogels containing free drug and those with ICs. The role of CD in the drug‐release process was not only due to its inclusion ability but also its effect on the polymer relaxation. GA, apart from crosslinking PVA, probably interacted with the cyclodextrins and, thereby, influenced the matrix structure and the drug‐release kinetics. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40318.     

Synthesis and characterization of novel pH‐responsive poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) hydrogels for drug delivery

In this study, N‐allylsuccinamic acid (NASA) was synthesized in a single step with a yield of 85%. Carboxylic acid containing NASA was characterized through Fourier transform infrared (FTIR) radiation and ¹H‐NMR and ¹³C‐NMR analysis, and then it was used for synthesis of poly(2‐hydroxylethyl methacrylate‐co‐N‐allylsuccinamic acid) [p(HEMA‐co‐NASA)] hydrogels. The structure of the obtained pH‐responsive p(HEMA‐co‐NASA) hydrogels were characterized with FTIR spectroscopy and scanning electron microscopy analysis, and their swelling characterization was carried out under different drug‐release conditions. In the application step of the study, the hydrogels were used for the in vitro release of vitamin B12 and Rhodamine 6G, which were selected as model drugs. We determined that the hydrogels used as a drug‐delivery matrix could release the drug they had absorbed under different release conditions (phosphate‐buffered saline, 0.9% NaCl, and pH 1.2) at high rates for time periods of up to 24 h. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 39660.     

Development and characterization of gelatin‐based hydrogels,emulsion hydrogels,and bigels: A comparative study

This study was designed to examine the physicochemical and electrical properties of gelatin‐based hydrogels, emulgels, and bigels. The chemical studies suggested an increase in hydrogen bonding in the emulgel and bigel when sesame oil (SO; representative vegetable oil) and SO organogel (OG; representative OG) were incorporated within the gelatin matrix. The emulgel and bigel showed better mechanical properties and higher electrical impedances compared to the hydrogel. The hydrogel showed similar swelling at pH 1.2 and 7.2. The swelling of the emulgel and bigel was higher at pH 7.2. The formulations were found to be highly hemocompatible; this indicated their biocompatible nature. Ciprofloxacin, a model antimicrobial drug, was incorporated within the formulations. The release of the drug was found to be diffusion‐mediated. The antimicrobial efficiency of all of the drug‐loaded formulations was found to be equivalent. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41502.     

Design and study of the potential of crosslinked cationic polymers as drug delivery systems for dermal application

Crosslinked carriers based on cationic monomer [2‐(acryloyloxy)ethyl]trimethylammonium chloride or 2‐(dimethylamino)ethyl methacrylate were developed and investigated as new platform for ibuprofen transdermal delivery. Series of networks of varied composition and structure were synthesized and characterized by FTIR spectroscopy and following swelling kinetics in different solvents. Dermal safety tests to examine the skin irritation and sensitization potential of the network films were performed in vivo. Chosen network compositions were loaded with ibuprofen by swelling in its ethanol solution. The structures of the drug carriers were investigated by scanning electron microscopy. Ibuprofen release from the developed drug delivery systems was followed in phosphate buffer solution at 37 °C. The investigation proved the feasibility of the developed cationic copolymer networks as effective platforms with modified ibuprofen release for potential dermal application. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018 , 135, 46420.     

Dextrin crosslinked with poly(lactic acid): A novel hydrogel for controlled drug release application

A new class of biodegradable crosslinked hydrogel, consisting of hydrophobic polylactic acid (PLA) and hydrophilic dextrin in presence of crosslinker N,N‐methylene bisacrylamide (MBA) has been synthesized by free‐radical polymerization technique using potassium persulfate (KPS) as initiator. By variation of crosslinker concentration, a series of hydrogels have been prepared and the optimized grade has been selected on the basis of higher crosslinking efficiency as well as lower equilibrium swelling characteristics, XRD analysis. The hydrogels have been characterized by FTIR spectra, ¹³C‐NMR spectra, CHN analysis, SEM analysis, swelling characteristics, and toxicity study. In vitro release study of model drugs (ciprofloxacin and ornidazole) from hydrogel matrix has been performed in various buffer solutions at 37°C. The drug release kinetics and mechanism have been studied using zero order, first‐order kinetic models, Korsemeyar–Peppas model, Higuchi model, Hixson–Crowell model, and nonlinear Kopcha model. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40039.     

Effect of network mesh size and swelling to the drug delivery from pH responsive hydrogels

pH responsive hydrogels are ideal platforms for numerous therapeutic delivery applications, including oral delivery, as they are capable of overcoming the many barriers that must be considered when creating an effective drug delivery system. Understanding of the innate hydrogel network structure and its swelling behavior at environmentally relevant conditions is vital for designing hydrogel network capable of effective controlled drug release. Herein, we explored how to expand traditional techniques of swelling and pore characterization to gain better insight into the performance of anionic microparticles composed of the poly(methyl methacrylate-co-acrylic acid) with varying molar percentage of 10, 20, and 30 mol% of MMA, for controlled release of low-molecular-weight drugs. By evaluating these carrier systems at environmental conditions, we can observe changes in swelling and pore size of the anionic hydrogel networks as a function of MMA, which was then correlated with the release profiles of the small-molecular-weight drug sodium nitrate. With the correlation of the swelling behavior of the networks and the release profiles, we demonstrated how the expansion of swelling parameters at relevant pH values provides further incite for evaluating for the optimal blend for controlled release. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48767.     

Preparation and evaluation of photocrosslinkable chitosan as a drug delivery matrix

Epichlorohydrin (1‐chloro‐2,3‐epoxypropane) was reacted with sodium azide in the presence of a phase transfer catalyst to obtain 1‐chloro‐2‐hydroxy‐3‐azidopropane, which was further coupled onto chitosan to prepare a photocrosslinkable derivative of the biopolymer. Elemental analysis and infrared (IR) spectroscopy confirmed the incorporation of azide groups onto chitosan. Films were cast from an aqueous acetic acid solution of azidated chitosan containing a model drug, such as theophylline. Irradiation of the film with ultraviolet (UV) light led to crosslinking of the drug incorporated film. IR spectra indicated complete surface crosslinking within 2 h of irradiation. Release of theophylline from uncrosslinked and crosslinked films was examined in simulated gastric and intestinal fluids without enzymes at 37 °C. The release of the drug from the crosslinked films was slower than the release from uncrosslinked films. Although the system is far from being optimized to obtain sustained release of a pharmacologically active agent for long periods, the data obtained indicate the possibility of developing photocrosslinkable matrices of biopolymers, such as chitosan, for sustained drug delivery with many advantages over chemical crosslinking. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1873–1877, 2002     

Evaluation of alginate–chitosan bioadhesive beads as a drug delivery system for the controlled release of theophylline

This study describes the preparation of mucoadhesive alginate–chitosan beads containing theophylline intended for colon‐specific delivery. The calcium alginate beads were coated with chitosan by the ionotropic hydrogelation method with a polyelectrolyte complex reaction between two oppositely charged polyions. The release profiles of theophylline from the beads were determined by ultraviolet–visible absorption measurement at 272 nm. Scanning electron microscopy was used for morphology observation. The in vitro mucoadhesive tests for particles were carried out with the freshly excised jejunum of Sprague‐Dawley rats. The bead particles, which ranged in size from 200 to 400 μm, exhibited excellent mucoadhesive properties. The results showed that the formulated coated beads succeeded in controlling the release of theophylline over a 24‐h period. In conclusion, the release of theophylline was found to be dependent on the composition of the beads, the component polymer and its possible interactions, and the bioadhesiveness. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009