Functionalization of sterculia gum for making platform hydrogels via network formation for use in drug delivery.

Recently, various advancements have been made in the development of functional polymeric materials for innovative applications. Herein this work, functionalization of sterculia gum (SG) was carried out via grafting of poly(2-(methacryloyloxy) ethyltrimethylammonium chloride) (METAC)-polyvinyl pyrrolidone (PVP) to develop hydrogel dressings as a platform for use in drug delivery (DD). The innovation of the present work is the exploration of inherent antioxidant and antimicrobial properties of the SG along with antimicrobial characteristic of poly(METAC) and PVP, to design the doxycycline encapsulated hydrogel dressings for better wound healing. FESEM, EDS and AFM analyzed the surface morphology of hydrogels. FTIR, 13C NMR and XRD inferred inclusion of poly(METAC)-PVP into polymers. 13C NMR confirmed the incorporation of poly(METAC) and PVP onto gum by the presence of a peak at 54.74 ppm because of methyl carbon attached to quaternary nitrogen of poly(METAC) and at 45.48 ppm due to the ring carbon of PVP along with FTIR peak at 949 cm-1 because of CN bending of quaternary nitrogen of poy (METAC). Thermal characterization of copolymers has been performed using TGA analysis. One gram of copolymeric hydrogel dressing absorbed 6.51 ± 0.03 g simulated salivary fluid (SSF) and 7.65 ± 0.03 g simulated wound fluid (SWF). Release of doxycycline drug occurred in a sustained manner and followed the Non-Fickian diffusion mechanism from hydrogels. The release profile was most effectively described by Hixon-Crowell kinetic model. Hydrogel demonstrated biocompatibility and expressed thrombogenicity 79.7 ± 4.9 % during its polymer-blood interactions. Copolymer revealed mucoadhesive property, requiring a force of 77.00 ± 0.01 mN to detach from bio-membrane. Additionally, it exhibited antioxidant features, showing 43.81 ± 0.286 % free radical scavenging. Hydrogel dressings were mechanically stable and revealed 0.76 ± 0.09 N mm-2 tensile strength and 9.18 ± 0.01 N burst strength. Polymer films were permeable to oxygen and water vapor and were impermeable to microorganisms. Hydrogel dressings exhibited antimicrobial properties against Pseudomonas aeruginosa and Staphylococcus aureus bacteria. Overall, these properties displayed the suitability of hydrogels for wound dressing (WD) applications which may actively enhance wound healing.

The centrifugal spinning of vitamin doped natural gum fibers for skin regeneration.

The study investigates the use of fiber carriers, based on biopolymeric gums as potential candidates for cosmetic and dermatological applications, in particular for skin regeneration. Gum arabic (GA), xanthan gum (XA), and gum karaya (GK) were used as the main gum materials for the fibers, which were prepared by centrifugal spinning from an aqueous solution. These solutions of different mass gum ratios were blended with poly (ethylene oxide) (PEO) for better spinnability. Finally, vitamins E and C were added to selected solutions of gums. The resulting fibers were extensively investigated. The morphology and structure of all fibers were investigated by scanning electron microscopy and Fourier transformed infrared spectroscopy. Most importantly, they were characterized by the release of vitamin E loaded in the fibers using UV-VIS spectroscopy. The presentation will show that the newly prepared fibers from GA and PEO represent a very promising material for cosmetic and dermatologic applications.

Novelkaraya gum micro-particles loaded Ganoderma lucidum polysaccharide regulate sex hormones, oxidative stress and inflammatory cytokine levels in cadmium induced testicular toxicity in experimental animals.

Presented research aimed to develop a spray drying process without the use of organic solvents for the preparation of novel Karaya gum polymer microparticles (MPs) of Ganoderma lucidum polysaccharide (GLP). The prepared microparticles were characterized and evaluated. Prepared novel karaya gum micro-particles loaded Ganoderma lucidum polysaccharide (GLP MPs) were observed an effect on cadmium (CAD) induced testicular toxicity. A total of 40 rats (male) was divided into 4 groups viz. 1. Control group, 2. GLP MPs (250 mg/kg, 60 days of b.w per day), 3. CAD (60 days of 30 mg/l/day), 4. GLP MPs + CAD. CAD was responsible for altering the sex hormones, oxidative stress and inflammatory cytokines. Furthermore, elevated levels of indicator of oxidative stress, malondialdehyde, and a reduced action of SOD, GSH, and CAT (antioxidant enzymes), were observed in the tissues of the testicles of CAD- treated group. Such harmful occurrences were followed by an up-regulation in proinflammatory cytokines (TNF-α, IL-1ß) levels, protein expression of Nrf2, and HO-1 expression was decreased. GLP MPs pre-treatment significantly abrogated these toxic effects which were confirmed histologically. This study concluded that pre-treatment with GLP MPs exerts a protective effect against CAD-induced male reproductive testicular toxicity.

Recent findings and future directions of grafted gum karaya polysaccharides and their various applications: A review.

Gum karaya is a polysaccharide that has several industrial applications in the pharmaceutical, food, and environmental fields owing to its hydrophilic, anionic, and biocompatible nature. Gum karaya and its modified forms have been assessed for drug delivery, wastewater treatment, and food industry applications. This review provides a comprehensive overview of various synthetic methods of modification of gum karaya, such as grafting initiated through free radical, microwave-assisted grafting, radiation-assisted, and enzyme-assisted modification methods. In addition, the review outlines collective industrial applications of modified gum karaya in drug delivery systems, removal of heavy atoms, dyes, food, and other biological activities, and suggests possible prospects for gum karaya modification and their remarkable industrial applications.

Characteristics of karaya gum based films: Amelioration by inclusion of Schisandra chinensis oil and its oleogel in the film formulation.

This research was focused to develop novel karaya gum films, modified by adding Schisandra chinensis oil and its oleogel. The films produced were assessed for physicochemical, mechanical, thermal and structural characteristics. Glass transition temperature (Tg) of control karaya gum films was recorded as 145.70 °C. Insignificant (p < 0.05) changes occurred in Tg of films in which oil was incorporated, irrespective of the concentration. However, Tg decreased significantly (p < 0.05) as oleogel was added to the karaya gum films and lowest Tg occurred for the KGOG3 films which contained highest concentration of oleogel. X-ray diffraction test depicted an obsolete amorphous behavior of control karaya gum film whereas some peaks appeared in other film samples. Scanning electron micrography (SEM) revealed a reduction in roughness and grainy morphology when oil or oleogel was added to the films. Addition of oil/oleogel enhanced the phenolic content and DPPH radical scavenging activity of the films.

Modified karaya gum colloidal particles for the management of systemic hypertension.

This study undertakes the development of colloidal carriers for the purpose of oral delivery of bosentan and subsequent management of systemic hypertension. Karaya gum, a natural polymer was carboxymethylated to improve its hydrophilic character and then the carboxymethyl gum was hydrophobically modified by forming propyl ethers. The modified polymer acquired amphiphilic property and self-aggregated in water to form amphiphilic colloidal particles (ACPs) at critical concentration of 3.35 mg/L with spherical shape (<200 nm) and smooth surface morphology. The colloidal particles could entrap >90% drug in the lipophilic domain. The ionic crosslinking of the hydrophilic shell of ACPs imparted greater stability to the colloidal system. The crosslinking extended the duration of drug release under simulated gastrointestinal fluids. The crystalline drug physically turned into amorphous state after hosting into the lipophilic cores of ACPs. The entrapment resulted in significant improvement of drug dissolution rate. The polymer relaxation contributed to the diffusion process of drug from ACPs. Pre-clinical testing via oral route demonstrated that the crosslinked colloidal particles could effectively control the systemic hypertension over a period of 12 h. Hence, bosentan-loaded self-assembled colloidal particles may advance the management of systemic hypertension.

Sterculia striata gum as a potential oral delivery system for protein drugs.

Natural polysaccharides have been investigated as vehicles for oral insulin administration. Because of their non-toxic, renewable, low cost and readily available properties, gums find multiple applications in the pharmaceutical industry. This work aimed to develop a Sterculia striata gum-based formulation associated with additional biopolymers (dextran sulfate, chitosan, and albumin), a crosslinking agent (calcium chloride) and stabilizing agents (polyethylene glycol and poloxamer 188), to increase the oral bioavailability of proteins. Insulin was used as a model drug and the methods used to prepare the formulation were based on ionotropic pregelation followed by electrolytic complexation of oppositely charged biopolymers under controlled pH conditions. The developed formulation was characterized to validate its efficacy, by the determination of its average particle size (622 nm), the insulin encapsulation efficiency (70%), stability in storage for 30 days, and the in vitro mucoadhesion strength (92.46 mN). Additionally, the developed formulation preserved about 64% of initial insulin dose in a simulated gastric medium. This study proposed, for the first time, a Sterculia striata gum-based insulin delivery system with potential for the oral administration of protein drugs, being considered a valid alternative for efficient delivery of those drugs.

Antibacterial and cytotoxic properties from esterified Sterculia gum.

Sterculia gums, as karaya and chicha gum, are complex branched and polydisperse heteropolysaccharides which can have their applications extended by improving their characteristics through chemical modifications. The objective of this work was to increase the antimicrobial activity of karaya and chicha gum through chemical modification with maleic anhydride. The incorporation of anhydride in the gum structure was confirmed by the characterization techniques. The derived biopolymers were synthesized and characterized by FTIR, X-ray diffraction, Thermogravimetric analysis and elemental analysis. Antimicrobial activity was evaluated against the Staphylococcus aureus strain (ATCC 25923). Mammalian cytotoxicity assays were also performed by MTT and hemolysis tests. The derivatives showed excellent antibacterial action inhibiting almost 100% of bacterial growth and did not present significant cytotoxicity in mammalian cells. The results showed that the derivatives are promising for biomedical applications aiming the control of infectious diseases caused by S. aureus.

Microwave assisted synthesis of karaya gum based montmorillonite nanocomposite: Characterisation, swelling and dye adsorption studies.

A polymer-clay hybrid composite material, (KG-g-PMETAC/MMT) has been synthesised by microwave assisted free radical polymerisation using modified karaya gum and clay mineral and was characterised by various techniques. The karaya gum has been modified by grafting with (2-methacryloyloxy ethyl) trimethyl ammonium chloride prior to making the clay composite. Montmorillonite was used as the clay component. The nanocomposite exhibited pH responsive swelling behaviour. The maximum swelling of 42.23 g/g was observed at pH 7.0 and minimum of 17.28 g/g was noticed at pH 9.2. The water transport mechanism was Fickian in nature and followed second order kinetic model. The adsorption capacities of the nanocomposite for the chosen cationic dyes, methylene blue (MB), toluidine blue (TB), crystal violet (CV) and azure B (AB) were found to 155.85, 149.64, 137.77 and 128.78 mg/g respectively. The dye adsorption was found to be a pseudo-first order kinetic process. The adsorption data is found to best fit with Freundlich isotherm model indicating heterogeneous adsorption and possibility of multilayer formation. Negative value of ΔG indicated the spontaneous nature of adsorption process at the temperatures under study. The reusability studies indicated that desorption of about 70% of the adsorbed dyes can be achieved after two consecutive cycles.

Synthesis and characterization of alginate and sterculia gum based hydrogel for brain drug delivery applications.

The present work deals with the design of the alginate, sterculia gum polysaccharide and PVP based hydrogel for brain drug delivery applications. The release dynamics of citicoline drug, a nerve regenerating agent, was evaluated. The polymers were investigated by Cryo-SEMs, AFM, FTIR, XRD, 13C NMR, and swelling studies. The drug release occurred slowly without burst effect and followed mechanism that was approaching the Fickian diffusion mechanism and first order kinetic model. The polymer matrix showed drug loading 40.0 ± 0.8%, thrombose percentage 68.70 ± 8.95%, hemolytic index value 3.66 ± 1.65%, detachment force from the intestinal mucosa = 0.124 ± 0.04 N, and tensile strength 7.67 ± 0.40 N/mm2. These films were found biocompatible, antioxidant and mucoadhesive and could be explored for brain drug delivery.

Eco-friendly synthesis and photocatalytic application of flowers-like ZnO structures using Arabic and Karaya Gums.

Flowers-like ZnO structures were synthesized using Arabic Gum (AGZnO) or Karaya Gum (KGZnO). The AGZnO and KGZnO were characterized by X-ray diffractometry, Fourier Transformed Infrared, Scanning Electron Microscopy, Photoluminescence, nitrogen adsorption/desorption and diffuse reflectance techniques. The materials were tested in the discoloration of Methylene Blue (MB) dye under visible light and scavenger studies were also performed. The toxicity of the MB irradiated was investigated in bioassays with Artemia salina. The structural characterization demonstrated the formation of hexagonal ZnO. All samples presented flower-like morphology with presence of mesopores identified by BET method. The optical properties indicated band gap of 2.99 (AGZnO) and 2.76 eV (KGZnO), and emission in violet, blue and green emissions also were observed. The KGZnO demonstrated better photocatalytic performance than the AGZnO, and scavenger studies indicated that OH radicals are the main species involved in the degradation of the pollutant model. The photodiscoloration of MB solution did not demonstrate toxicity. Therefore, KGZnO is a promising material for photocatalysis application.

Study of a cross-linked hydrogel of Karaya gum and Starch as a controlled drug delivery system.

A cross-linked hydrogel was synthesized using a hybrid backbone of karaya gum starch and grafted with polyacrylic acid. It showed a maximum swelling ratio (SR) of 30.5 g/g at pH 10 and was explored as an oral drug delivery carrier using paracetamol and aspirin as model drugs. In vitro release experiments revealed that maximum drug release at pH 7.4 in comparison to pH 1.2 (simulated intestinal vs gastric fluid) and neutral medium. The release profiles of these drugs showed no initial burst. It also showed good hemocompatibilty and non-cytotoxicity for its employment as a site specific drug delivery agent.

Novel propyl karaya gum nanogels for bosentan: In vitro and in vivo drug delivery performance.

The amphiphilic propyl Karaya gum (KG) with a degree of propyl group substitution of 3.24 was synthesized to design self-assembled nanogels as carriers for bosentan monohydrate, a poorly soluble antihypertensive drug. The drug was physically hosted into the hydrophobic core of the micellar nanogels by solvent evaporation method. TEM images revealed spherical shape and core-shell morphology of the nanogels. Depending upon polymer: drug weight ratio, the drug entrapment efficiency of >85% was attained. The carriers had hydrodynamic diameter in the range of 230-305 nm with narrow size distribution. The zeta potential of -23.0 to -24.9 mV and low critical association concentration (CAC) of 8.32 mg/l provided evidence that the colloidal nanogel system was physically stable. Thermodynamics of the propyl KG system in water favored spontaneous self-assembly of propyl KG. FTIR, thermal and x-ray analyses suggested that the drug was compatible in the hydrophobic confines of the nanogels. The micellar nanogels liberated their contents in simulated gastrointestinal condition in a pH-dependent manner over a period of 10 h. Peppas-Sahlin modeling of in vitro drug release data suggested that the polymer relaxation/swelling mechanism dominated the drug release process. Pre-clinical testing of the mucoadhesive nanogel formulations exhibited that the system could monitor the anti-hypertensive activity for a prolonged period. Overall, this propyl KG micellar nanogel system had a great potential and splendid outlook to serve as novel oral controlled release carriers for poorly soluble drugs with outstanding pharmacodynamics.

Smart karaya-locust bean gum hydrogel particles for the treatment of hypertension: Optimization by factorial design and pre-clinical evaluation.

This investigation was undertaken to unveil the controlled drug delivery and preclinical anti-hypertensive potential of a novel interpenetrating biopolymer-based network of karaya gum and carboxymethyl locust bean gum (CLBG). The Williamson synthesis of CLBG was confirmed after analyzing FTIR spectra, degree of O-carboxymethyl group substitution and viscosity. The hydrogel particles (HPs) were developed using aluminium chloride solution as cross-linker. A full 32 factorial design approach was adopted for the optimization of two responses: drug entrapment efficiency and drug release (%) in simulated gastrointestinal conditions at 10 h. FE-SEM images and EDX spectra supported the formation of spherical HPs and successful entrapment of the drug in the HPs. Depending upon formulation variables, the drug entrapment efficiency of the HPs lied in the range of 84-98%. The HP matrix was chemically compatible for carvedilol phosphate as was suggested by infrared, thermal and x-ray analyses. The swelling kinetics of HPs corroborated well with the pH-dependent in vitro drug discharge characteristics. The drug release from HPs was found to follow anomalous transport mechanism with varying contribution of simple diffusion and polymer relaxation as was elucidated by Peppas-Sahlin model equation. Preclinical data suggested that the optimized HPs had an excellent blood pressure lowering activity in male Swiss albino mice up to 10 h.

Karaya gum-graft-poly(2-(dimethylamino)ethyl methacrylate) gel: An efficient adsorbent for removal of ionic dyes from water.

In the present study, a novel hydrogel based on the polysaccharide, 'Karaya gum' has been synthesised by graft copolymerization and evaluated as an adsorbent for the removal of ionic dyes from aqueous solution. The hydrogel was made by simultaneous grafting and cross linking of Karaya gum using 2-(dimethylamino)ethyl methacrylate (DMAEMA) and N,N'-methylene-bis-acrylamide via microwave irradiation. The graft copolymer gel was characterized by FTIR, TGA, SEM techniques. The swelling of the gel studied in buffer media of varying pH revealed a pH responsive behaviour with a maximum swelling in neutral pH and a minimum swelling at pH 1.2. The temperature dependent swelling study indicated 40 °C as the lowest critical solution temperature. Kinetic studies indicated the swelling to be a second order process with Fickian diffusion as the water transport mechanism. The adsorption studies indicated maximum adsorption capacity of 89.28 and 101.42 mg/g towards methylene blue and indigo carmine respectively. The dye adsorption data is found to fit well with pseudo- second order kinetic model and the Freundlich adsorption isotherm model. The adsorption was found to be a multistep process with surface adsorption followed by intraparticle diffusion. Thermodynamic studies revealed the adsorption of dyes to be spontaneous.

Modification of sterculia gum polysaccharide via network formation by radiation induced crosslinking polymerization for biomedical applications.

AIMS: Keeping in view the therapeutic and pharmaceutical applications of sterculia gum polysaccharide in consideration, its modification has been carried out through grafting and crosslinking to develop the hydrogels for enhanced biomedical applications. Radiation method was used for formation of sterile network of sterculia gum, carbopol and graphene oxide (GO). These polymers were characterized by Cryo-SEMs, AFM, 13C NMR solid state, swelling studies. Some biomedical properties of hydrogels like thrombogenicity, haemolytic potential, antioxidant activity, mucoadhesion and gel strength were determined along with the drug delivery studies. SCOPE: In the present work, sterile polysaccharide gum based drug delivery system was developed for the slow delivery of gemcitabine, an anti-cancer drug, to overcome its side. CONCLUSIONS: The release profile of anti-cancer drug "gemcitabine" followed non-Fickian diffusion mechanism and release profile was best fitted in Korsmeyer-Peppas kinetic model of drug release. The hydrogels were found to be non-thrombogenic, non-haemolytic, mucoadhesive and antioxidant in nature. Incorporation of the GO nano-sheets in the composite hydrogel matrix has improved its mechanical and drug delivery properties and also exerted strong influence on the network density and mesh size of the hydrogels.

Sterculia and Brachychiton: a comprehensive overview on their ethnopharmacology, biological activities, phytochemistry and the role of their gummy exudates in drug delivery.

OBJECTIVES: Sterculia and Brachychiton are two related genera (Malvaceae) containing more than 300 species. Most of these species are ornamental trees that are native to Australia and widely cultivated in many countries. Different members of the two genera were used by various cultures for medicinal and economical purposes. This review sheds light on the medicinal values and chemical composition of various species of these two genera. KEY FINDINGS: Sterculia and Brachychiton species were used traditionally for the treatment of gastrointestinal disorders, microbial infection, skin diseases, inflammation and many other conditions. The seeds of various species were roasted and eaten by many traditional tribes. Plants from the two genera revealed their anti-inflammatory, antioxidant, antimicrobial, antidiabetic, antiulcer, insecticidal and analgesic activity. These activities may be attributed to the presence of a wide range of secondary metabolites as flavonoids, phenolic acids, coumarins, terpenoids particularly sesquiterpenes and triterpenes in addition to sterols and fatty acids. Moreover, the gummy exudates obtained from some members of these genera played an important role in different pharmaceutical dosage forms and drug-delivery systems. CONCLUSIONS: More research is recommended on other species of Sterculia and Brachychiton to discover new molecular entities with potential biological and economic values.

Formulation and in vitro evaluation of sustained release matrix tablets using cross-linked natural gum.

Polysaccharide gums because of their biocompatibility, biodegradability and non-immunogenic properties are considered as the best choice for preparing sustained release tablets as compared to their synthetic counterpart. The cross linking of natural gums in matrix tablets increase the sustained release property of matrix tablets. Isoniazid is a first line therapy of tuberculosis, belongs to BCS I with half-life of 3-4 hours. These characteristics make isoniazid a good candidate for sustained release dosage form. Karaya gum crossed linked with trisodium tri metaphosphate was used as release rate retardant for preparing isoniazid cross-linked matrix tablet. Total 8 sustained release formulations were prepared. Both granules and tablets were evaluated under in vitro condition against different parameters. Dissolution studies were performed with all eight formulations for 12 hours using USP apparatus I. Four formulations designated as F1, F2, F3, F4 have drug and karaya gum while other four formulations F5, F6, F7, F8 have drug and crossed linked polymer in ratios of 1:1, 1:2, 1:3 and 1:4 respectively. Dissolution data was analyzed by using different kinetic models. Best fit model for most efficient formulation was zero order while release mechanism was super case I. Formulation 8 showed sufficiently slow release kinetics and about 83% of drug was released in 10 hours, indicating that cross-linked karaya gum proved efficient in preparing sustained release tablets.

Functionally modified polyacrylamide-graft-gum karaya pH-sensitive spray dried microspheres for colon targeting of an anti-cancer drug.

An effort was made to formulate and evaluate pH-sensitive spray dried microspheres using hydrolyzed polyacrylamide-graft-gum karaya (PAAm-g-GK) for colon specific delivery of an anti-cancer agent, capecitabine. The synthesis of pH-sensitive PAAm-g-GK copolymer was done by free radical polymerization followed by alkaline hydrolysis and characterized satisfactorily. The microspheres were spherical in shape; drug entrapment efficiency was found to be in the range of 77.30% to 88.74%. Pulsatile swelling study indicates that the PAAm-g-GK consists of considerable pH-sensitivity. The in-vitro drug release suggested that the microspheres prepared using native GK were incapable to retard the drug release within 5h in the environment of stomach and small intestine. While, those microspheres prepared using pH-sensitive PAAm-g-GK copolymer having crosslinked with glutaraldehyde (GA), released little amount of drug within 5h, but maximum amount of drug was targeted to colonic region in a controlled manner up to 24h. For example, GK10 Microspheres showed only 19.16% drug release at the end of 5th h, while about 80.14% of drug was targeted to colonic region. Cross-linking with GA reduced the early drug release in the upper part of gastrointestinal tract and guaranteed maximum drug release in the colonic region. A rapid enhancement in drug release was witnessed in rat caecal content medium due to the action of colonic bacteria on PAAm-g-GK copolymer.

Influence of graphene-oxide nanosheets impregnation on properties of sterculia gum-polyacrylamide hydrogel formed by radiation induced polymerization.

Present work is an attempt, to explore the potential of graphene oxide nanoplates impregnation, on the mechanical and drug delivery properties of sterculia gum-polyacrylamide composite hydrogel formed by radiation induced polymerization. These polymers were characterized by SEM, cryo-SEM, AFM, FTIR's, 13C NMR and swelling studies. Release profile of an anticancer drug 'gemcitabine' was studied to determine the drug release mechanism and best fit kinetic model. Furthermore, some important biomedical properties of the polymers such as blood compatibility, mucoadhesion, antioxidant properties and gel strength were also studied. Impregnation of GO into sterculia gum-poly(AAm) hydrogels decreased the swelling of hydrogels but improved the mechanical, drug loading and drug release properties of the hydrogels. Release of gemcitabine from drug loaded hydrogels occurred through non-Fickian diffusion mechanism and release profile was best fitted in first order kinetic model. These hydrogels have been found as haemocompatible, mucoadhesive, and antioxidant in nature.