Evaluation of natural gum-based cryogels for soft tissue engineering.

In this study, three natural biomaterials, Locust bean gum (LBG), Xanthan gum (XG), and Mastic gum (MG), were combined to form cryogel scaffolds. Thermal and chemical characterizations revealed the successful blend formation from LBG-XG (LX) and LBG-XG-MG (LXM) polymers. All blends resulted in macro-porous scaffolds with interconnected pore structures under the size of 400 µm. The swollen cryogels had similar mechanical properties compared with other polysaccharide-based cryogels. The mean tensile and compressive modulus values of the wet cryogels were in the range of 3.5-11.6 kPa and 82-398 kPa, respectively. The sustained release of the small molecule Kartogenin from varying concentrations and ratios of cryogels was in between 32 and 66% through 21 days of incubation. Physical, mechanical, and chemical properties make LX and LXM polysaccharide-based cryogels promising candidates for cartilage and other soft tissue engineering, and drug delivery applications.

Optimization, in vitro release and toxicity evaluation of novel pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum semi-interpenetrating networks.

BACKGROUND: In recent era, pH sensitive polymeric carriers that combines the materials engineering and medicine is gaining researcher's attention as they maximizes drug concentration at site of absorption and reduces side effects for e.g. orally administered cetirizine HCl (CTZ HCl) upsets the stomach and furthermore shows high intestinal absorption. Thus, development of pH sensitive hydrogels with sufficient mechanical strength will be good candidate to address this issue. METHODS: Here, we developed pH sensitive itaconic acid-g-poly(acrylamide)/sterculia gum (IA-g-poly(AM)/sterculia gum) semi-interpenetrating network (semi-IPN) by free radical polymerization technique for intestinal delivery of CTZ HCL. RESULTS: Optimized formulation (I5) with 6% w/w IA showed negligible swelling at pH 1.2, and maximum swelling at pH 7.4. Solid state characterization of optimized formulation showed successful development of semi-IPN structure and incorporation of drug without any noticeable drug-carrier interaction. In vitro release study showed biphasic pH dependent release of CTZ HCl, where initial burst release was observed at acidic pH followed by sustained release at basic pH. Acute oral toxicity and histopathological studies confirmed the non-toxic nature of IA-g-poly(AM)/sterculia gum. CONCLUSION: Conclusively, developed biocompatible semi-IPN hydrogels with sufficient pH sensitivity and mechanical strength could serve as a potential carrier for intestinal delivery of CTZ HCL to maximize its absorption and reduce side effects.

Synthesis and characterization of scaffolds produced under mild conditions based on oxidized cashew gums and carboxyethyl chitosan.

This study describes the development of scaffolds based on carboxyethyl chitosan (CEC) and different oxidized cashew gums (CGOx) for tissue engineering (TE) applications. After the physico-chemical characterizations of CEC and CGOx (oxidation degree of 20, 35 and 50%), these macromolecules were used for producing the CGOx-CEC hydrogels through a Schiff base reaction, in the absence of any crosslinking agent. The CGOx-CEC scaffolds obtained after a freeze-drying process were characterized for their morphology, mechanical properties, swelling ability, degradation, and porosity. Those revealed to be highly porous (25-65%), and showed a stable swelling behavior, as well as degradation properties in the absence of enzymes. The use of the cashew gum with higher degree of oxidation led to scaffolds with higher crosslinking densities and increased compressive modulus. None of the hydrogels show cytotoxicity during the 14 days of incubation. Considering all the properties mentioned, these scaffolds are excellent candidates for soft tissue regeneration, owing to the use of eco-friendly starting materials and the easy tuning of their properties.

Acacia mearnsii gum: A residue as an alternative gum Arabic for food stabilizer.

Acacia mearnsii gum is not commercially exploited, being characterized as residue from A. mearnsii cultivation. This work investigated the A. mearnsii gum polysaccharide composition, its cytotoxicity and the technological effect as a stabilizer in ice cream. A. mearnsii gum showed a similar chemical structure to commercial gum Arabic and did not decrease the viability and proliferation of fibroblast cells (Balb/3T3) and hepatocarcinoma (HepG2). Rheological tests showed that the ice cream stabilized by the A. mearnsii gum had a more structured system (more interactions between the mixture components) and the same melting characteristics as the ice cream samples made with commercial gum Arabic. The results showed that A. mearnsii gum, which is actually an agro-industrial residue from tannin production for industry, is a potential stabilizing gum for the food industry, contributing to the economic development of the exploitation chain of A. mearnsii products and by-products.

In vitro evaluation of reactive nature of E- and Z-guggulsterones and their metabolites in human liver microsomes using UHPLC-Orbitrap mass spectrometer.

Guggulipid is known to be useful for hypercholesterolemia, arthritis, acne, and obesity. These activities are attributed to its two principal isomeric active constituents, viz., E- and Z-guggulsterones. There are several side effects reported for guggulipid, which include widespread erythematous papules in a morbilliform pattern and macules localized to the arms; swelling and erythema of the face with burning sensation; pruritis; and bullous lesions on the lower legs with associated headaches, myalgia and itching. We hypothesized that one probable reason for these toxic reactions could be the formation of electrophilic reactive metabolites (RMs) of guggulsterones and their subsequent reaction with cellular proteins. Unfortunately, no report exists in the literature highlighting detection of RMs of guggulsterone isomers. Accordingly, the present study was undertaken to investigate the potential of E- and Z-guggulsterones to form RMs in human liver microsomes (HLM) using glutathione (GSH) and N-acetylcysteine (NAC) as trapping agents. The generated samples were analysed using ultra-high performance liquid chromatography (UHPLC) coupled to an Orbitrap mass spectrometer. The analysis of incubations with trapping agents highlighted that hydroxylated metabolites of guggulsterone isomers showed adduction with GSH and NAC. Even direct adducts of guggulsterone isomers were observed with both the trapping agents. The in silico toxicity potential of E- and Z-guggulsterones and their RMs was predicted using ADMET Predictor™ software and comparison was made against reported toxicities of guggulipid.

Engineering butylglyceryl-modified polysaccharides towards nanomedicines for brain drug delivery.

Colloidal systems prepared from carbohydrates are subject of intense research due to their potential to enhance drug permeability through biological membranes, however their characteristics and performance are never compared directly. Here we report the results of a comparative investigation of a series of butylglyceryl-modified polysaccharides (chitosan, guar gum, and pullulan) that were formulated into nanoparticles and loaded with a range of model actives (Doxorubicin, Rhodamine B, Angiotensin II). Butylglyceryl-modified guar gum and corresponding pullulan nanocarriers were more stable at physiological pH compared to those obtained from modified chitosan, and studies of the in-vitro interactions with mouse brain endothelial cells (bEnd3) indicated an increased biological membrane permeability and lack of toxicity at application-relevant concentrations. No significant haemolytic effect was observed, and confocal microscopy and flow cytometry studies confirmed the efficient cellular uptake and cytoplasmic localisation of NPs. Most promising characteristics for brain drug delivery applications were demonstrated by butylglyceryl pullulan nanocarriers.

Toxicity studies of a gum guggul extract formulation administered by gavage to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice.

Gum guggul extracts (GGEs) are botanical preparations derived from the oleoresin of the Commiphora mukul tree. The preparations are traditionally used in Ayurvedic medicine to treat hyperlipidemia, obesity, diabetes, atherosclerosis, and inflammatory conditions such as arthritis. In the United States, GGEs are marketed as dietary supplements. GGE toxicity was evaluated due to widespread human exposure through increasing dietary supplement use, demonstrated metabolic and hormone-altering effects, and a lack of available information to adequately assess safe use in humans. Male and female Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice were administered a GGE formulation in corn oil by gavage for 28 days or 3 months. Oral gavage was chosen as the route of exposure for these studies because human exposure primarily occurs by ingestion of encapsulated GGE supplements. (Abstract Abridged).

Acrylamide grafted neem (Azadirachta indica) gum polymer: Screening and exploration as a drug release retardant for tablet formulation.

The study was initiated with the intent to synthesize acrylamide grafted neem gum polymer (AAm-g-NG), and screen its drug release retardation ability both in vitro and in vivo. Different batches (NGP-1 to NGP-9) of tablet formulation were prepared by varying polymer concentration using propranolol HCl and compared with HPMC K100 M and marketed SR tablets. FTIR study proved the grafting phenomenon and showed no incompatibility between AAm-g-NG and propranolol HCl. AAm-g-NG showed significant swelling and water retention capacity than NG. AAm-g-NG was found to be biodegradable and exhibited no toxicity to Artemia salina. After 12 h, NGP-6 showed non-significant (p > 0.05; f2= ∼ 90) percent drug release (80.52 ±â€¯3.41%) compare to marketed formulation (79.65 ±â€¯4.08%). Significant swelling of the matrix caused slower diffusion of the drug. NGP-6 and marketed formulation in rabbits showed the non-significant difference between Cmax and Tmax, hence NGP-6 meets the requirement of sustained-release tablets.

Synthesis and evaluation of hydrophobically modified fenugreek gum for potential hepatic drug delivery.

The objective of this study was to hydrophobically modify fenugreek gum (FG) and to further evaluate the potential application of the obtained derivative in liver-targeted drug delivery system. Stearic acid (C18) was conjugated with FG (FG-C18) by a simple esterification reaction. The obtained FG-C18 was then characterized on its chemical structure by Fourier transform infrared spectroscopy and 1H-nuclear magnetic resonance. The self-assembled nanomicelles (NMs) of FG-C18 in water were prepared by an ultrasonication method. The average diameter and zeta potential of FG-C18 NMs were 196.70 ± 6.12 nm and -31.79 ± 1.58 mV, respectively. FG-C18 NMs appeared as spherical particles under transmission electron microscopy and possessed a critical micellar concentration of 0.042 mg/ml by pyrene fluorescence probe method. A low toxicity of FG-C18 was revealed on both HepG2 and MCF-7 cells at 0.1-100 mg/ml. Haemolysis of FG-C18 was less than 5%. Cellular uptake of coumarin-6 into HepG2 cells was enhanced by treating with C6-loaded FG-C18 NMs compared to free coumarin-6. These results suggest that FG-C18 have a potential application for a liver targeted drug delivery.

Phenolics composition, antioxidant properties and toxicological assessment of Prosopis alba exudate gum.

The objective of this work was to deepen on the study of functional properties of the phytochemicals present in Prosopis alba exudate gum (G), as well as to rule out possible adverse effects of some of its components. Commonly employed purification methods were compared. Filtration prevents further loss of potentially bioactive compounds. The filtrated gum showed a higher concentration of phenolics, flavonoids and tannins than arabic gum, which was correlated with better in vitro antioxidant properties. Particularly, tannins, commonly considered as toxic compounds in exudate gums, were found in lower concentration than in others gums obtained from genus Prosopis and Acacia. The toxicological evaluation performed on rats did not show symptoms of intoxication associated with the administration of the gum. These results provide useful evidence to support the potential use of G as a safe functional food additive with the added benefit of taking advantage of a non-exploited natural resource.

Mucoadhesive guargum hydrogel inter-connected chitosan-g-polycaprolactone micelles for rifampicin delivery.

Natural polymer guar gum has one of the highest viscosities in water solution and hence, these are significantly used in pharmaceutical applications. Guar gum inter-connected micelles as a new carrier has been developed for poor water soluble rifampicin drug. The hydrogel inter-connected micelle core was formulated as a hydrophilic inner and hydrophobic outer core by using guar gum/chitosan/polycaprolactone and the carrier interaction with rifampicin was confirmed by FT-IR. The morphological observations were carried out through TEM, SEM and AFM analysis. The encapsulation efficiency and in-vitro drug release behavior of prepared hydrogel based micelle system was analyzed by UV-vis spectrometry. The anti-bacterial activity against K. pneumoniae and S. aureus was studied by observing their ruptured surface by SEM. The cytotoxicity study reveals that the pure polymeric system has no toxic effect whereas drug loaded ones showed superior activity against THP-1 cells. From the cell apoptosis analyses, the apoptosis was carried out in a time dependent manner. The cell uptake behavior was also observed in THP-1 cells which indicate that the hydrogel based micelle system is an excellent material for the mucoadhesive on intracellular alveolar macrophage treatment.

Smart wound dressing based on κ-carrageenan/locust bean gum/cranberry extract for monitoring bacterial infections.

A smart wound dressing based on carrageenan (κC), locust bean gum (LBG), and cranberry extract (CB) for monitoring bacterial wound infections was developed and characterized using UV-vis spectroscopy, FT-IR, and SEM. The mechanical, swelling, cytotoxic and pH sensor properties were also investigated. UV-vis spectra demonstrated that the obtained κC:LBG:CB hydrogel film exhibited a visible change of colors as it was immersed in PBS solution pH 5.0, 7.3 and 9.0. The spectra of FT-IR suggested that chemical interactions had occurred between κC and CB extract. The obtained κC:LBG:CB hydrogel film exhibited adequate mechanical properties and a swelling behavior dependent on pH. Cytotoxicity tests indicated that κC:LBG:CB hydrogel film had dose-dependent cytotoxicity against NIH 3T3 fibroblast cells. The in vitro studies using Staphylococcus aureus and Pseudomonas aeruginosa demonstrated that the color changes of the κC:LBG:CB hydrogel film could be observed by naked eyes, confirming the potential use of the obtained hydrogel film as a visual system for monitoring bacterial wound infections.

Modifiable natural gum based microgel capsules as sustainable drug delivery systems.

Few hundred micrometer size microgel capsules from natural locust bean gum (LBG) was synthesized by means of divinyl sulfone (DVS) crosslinking in a surfactant free cyclohexane medium with 100% yield in 1 h. These LBG microgel capsules were chemically modified with different numbers of linear amine containing modifying agents such as ethylenediamine (EDA), diethylenetriamine (DETA), triethylenetetraamine (TETA) and branched polyethyleneimine (PEI) to induce cationic character for LBG microgels. The biggest change in zeta potential of LBG microgels that is +44.9 mV from -17.67 mV was observed upon the modification of LBG microgels with branched PEI (LBG/PEI). The blood compatibility studies were revealed that bare LBG microgels possess a good blood compatibility with non-hemolytic value, 0.96 ± 0.15%, and high blood clotting index, 87.35 ± 4.10%, whereas the blood compatibility of LBG/PEI microgels was found to be slightly-hemolytic, 4.96 ± 1.03%, and also moderate blood clotting index, 65.98 ± 98%. Additionally, sodium diclofenac (SDC) as a model drug was loaded into the LBG based microgels by directly loading from solution (absorption) and by chemical conjugation methods for in vitro release studies at physiological conditions, pH 7.4 at 37.5 °C A longer, and sustainable drug release profiles were obtained from chemical drug conjugated LBG microgels and the amine modified LBG microgels.

Gugulipid causes hypercholesterolemia leading to endothelial dysfunction, increased atherosclerosis, and premature death by ischemic heart disease in male mice.

For proper cholesterol metabolism, normal expression and function of scavenger receptor class B type I (SR-BI), a high-density lipoprotein (HDL) receptor, is required. Among the factors that regulate overall cholesterol homeostasis and HDL metabolism, the nuclear farnesoid X receptor plays an important role. Guggulsterone, a bioactive compound present in the natural product gugulipid, is an antagonist of this receptor. This natural product is widely used globally as a natural lipid-lowering agent, although its anti-atherogenic cardiovascular benefit in animal models or humans is unknown. The aim of this study was to determine the effects of gugulipid on cholesterol homeostasis and development of mild and severe atherosclerosis in male mice. For this purpose, we evaluated the impact of gugulipid treatment on liver histology, plasma lipoprotein cholesterol, endothelial function, and development of atherosclerosis and/or ischemic heart disease in wild-type mice; apolipoprotein E knockout mice, a model of atherosclerosis without ischemic complications; and SR-B1 knockout and atherogenic-diet-fed apolipoprotein E hypomorphic (SR-BI KO/ApoER61h/h) mice, a model of lethal ischemic heart disease due to severe atherosclerosis. Gugulipid administration was associated with histological abnormalities in liver, increased alanine aminotransferase levels, lower hepatic SR-BI content, hypercholesterolemia due to increased HDL cholesterol levels, endothelial dysfunction, enhanced atherosclerosis, and accelerated death in animals with severe ischemic heart disease. In conclusion, our data show important adverse effects of gugulipid intake on HDL metabolism and atherosclerosis in male mice, suggesting potential and unknown deleterious effects on cardiovascular health in humans. In addition, these findings reemphasize the need for rigorous preclinical and clinical studies to provide guidance on the consumption of natural products and regulation of their use in the general population.

Acetylated cashew gum-based nanoparticles for transdermal delivery of diclofenac diethyl amine.

Nanoprecipitation and dialysis methods were employed to obtain nanoparticles (NPs) of acetylated cashew gum (ACG). NPs synthesized by dialysis showed greater average size compared to those synthesized by nanoprecipitation, but they presented improved stability and yield. NPs were loaded with diclofenac diethylamine and the efficiency of the drug incorporation was over 60% for both methods, for an ACG:NP a weight ratio of 10:1. The cytotoxicity assay demonstrated that the NPs had no significant effect on the cell viability, verifying their biocompatibility. The release profile for the diclofenac diethylamine associated with the ACG-NPs showed a more controlled release compared to the free drug and a Fickian diffusion mechanism was observed. Transdermal permeation reached 90% penetration of the drug.

Safety Assessment of Galactomannans as Used in Cosmetics.

The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the safety of 16 galactomannans as used in cosmetics. These ingredients are legume polysaccharides that function mostly as hair/skin-conditioning agents and viscosity-increasing agents in cosmetic products. Their substantial molecular sizes suggest that skin penetration of these ingredients would be unlikely. The Panel concluded that these galactomannans are safe in the present practices of use and concentration described in this safety assessment.

Physicochemical characterization and toxicological evaluation of plant-based anionic polymers and their nanoparticulated system for ocular delivery.

The water-soluble fractions of mucilages and gum from the seeds of fenugreek, isphagula and mango bark exudate were isolated, purified and characterized using X-ray diffraction (XRD) spectrometry, Fourier transform infrared spectroscopy (FT-IR), maldi/GC-MS, elemental analysis, 1D ((1)H and (13)C) and 2D (HMQC, COSY) nuclear magnetic resonance spectroscopy (NMR). The fenugreek mucilage was identified to be a galactomannan chain consisting of 4 units of galactose attached to the backbone of 6 mannose units in 1:1.5 ratio. The isphagula mucilage was identified to be an arabinoxylan polysaccharide chain consisting of 4 units of arabinofuranose attached to the backbone of 9 xylopyrannose units in 1:3 ratio. The mango gum showed the presence of amylose, α-arabinofuranosyl and ß-galactopyranosyl, respectively. The characterized mucilages and gum were individually formulated into nanoparticulate system using their complementarily charged polymer chitosan. The particles were observed to be spherical in shape in the range of 61.5-90 nm having zetapotential between 31 and 34 mV and PDI of 0.097-0.241. The prepared nanoparticles were observed to be nonirritant and nontoxic in vitro and in vivo upto 2000 µg/ml. Therefore, these mucilages and gum can be the alternatives of anionic polymers for the ocular drug delivery system.

A comprehensive evaluation of the toxicology of the "Deli" cast sheet process used in experimental cigarettes.

CONTEXT: Manufacture of cigarettes results in tobacco by-products, some of which can be processed and added back to cigarettes. Such additions (known as reconstituted tobacco or reconstituted leaf) have been shown to reduce tar yields. A new process (termed "Deli" cast sheet) is a potential refinement of the reconstitution process. OBJECTIVE: Compare toxicity of smoke from experimental cigarettes made with reconstituted leaf with that from cigarettes made with Deli cast sheet. MATERIALS AND METHODS: Analytical chemistry, Salmonella mutagenicity and cytotoxicity assays were used to evaluate the composition biological activity of mainstream smoke from experimental cigarettes made with Deli cast sheet or with reconstituted leaf. The effect of different amounts of guar and propylene glycol in Deli cast sheet was also evaluated. RESULTS: Small increases in the amount of nitrogen oxides were found as a result of inclusion of the Deli cast sheet when compared with reconstituted leaf; no differences in cytotoxicity or mutagenicity were found. CONCLUSION: The Deli process neither significantly modified chemical composition of smoke nor affected its biological activity, as measured by the mutagenicity and cytotoxicity assays used here.

Guggulipid of Commiphora mukul, with antiallodynic and antihyperalgesic activities in both sciatic nerve and spinal nerve ligation models of neuropathic pain.

CONTEXT: Guggulipid is a neutral fraction of ethyl acetate extract of gum resin of the tree Commiphora mukul Engl. (Burseraceae) and used in Ayurvedic medicine for treatment of neurological disorders. OBJECTIVES: The present study was undertaken to assess the antiallodynic and antihyperalgesic activities of guggulipid in rats. MATERIALS AND METHODS: The screening study included the CCI and L5-L6 SNL models of neuropathic pain. Guggulipid (100 and 50 mg/kg) or saline was administered intraperitoneally in a blinded, randomized manner from postoperative day (POD) 7 to 13. Paw withdrawal duration (PWD) to spontaneous pain, chemical allodynia and mechanical hyperalgesia and paw withdrawal latency (PWL) to mechanical allodynia and thermal hyperalgesia were tested before surgery, before and after guggulipid or saline administration (from POD7 to 13) and after the withdrawal of treatment (from POD14 to 20). RESULTS: The activity profiles of the different doses of guggulipid were found to vary with time. In CCI rats, guggulipid (100 and 50 mg/kg) significantly (p < 0.05) reduced the spontaneous pain, mechanical allodynia and mechanical and thermal hyperalgesia responses and the LD50 of guggulipid was 1600 mg/kg. In SNL rats, both doses of guggulipid were found to be ineffective in reversing the spontaneous pain but showing antiallodynic and antihyperalgesic activity. DISCUSSION AND CONCLUSION: The results demonstrated that guggulipid produce antinociception in the peripheral nerve injury (CCI and SNL) models of neuropathic pain. The underlying mechanisms are expected to be modulating microglial activation occurring due to peripheral nerve injury.

Evaluation of 90-day oral rat toxicity studies on the food additive, gum ghatti.

Gum ghatti, a polysaccharide of natural origin, is used in foods as a thickening, gelling, emulsifying and stabilizing agent. In a 90-day toxicity study following Organization for Economic Co-operation and Development (OECD) Guideline #408, male and female Sprague-Dawley rats were exposed to 0 (control), 0.5, 1.5 and 5% gum ghatti in AIN-93M basal diet. Expected changes included increased full and empty cecal weights in 5% groups. Incidentally 2/10 females from the 5% gum ghatti group had a single colon ulcer with associated acute inflammation. In a second 90-day study increased cecal weights were present in Sprague-Dawley females exposed to 5% gum ghatti in AIN-93M and NIH-07 basal diets. A single colon ulcer with associated acute inflammation occurred in 1/20 control females given AIN-93M basal diet. The colon ulcers were considered a sporadic change possibly attributable to AIN-93M basal diet. In the second study a few statistically significant alterations in clinical chemistry were considered sporadic and unrelated to treatment. Feed consumption among treated and control groups was similar for each sex. Gum ghatti intake at the 5% dietary level ranged from 3044 to 3825mg/kg body weight/day. The 5% dietary administration was a NOAEL in both studies. NOAELs for males and females in the first study were 3044 and 3309mg/kg/day, respectively. NOAELs for females in the second study were 3670 and 3825mg/kg/day for AIN-93M and NIH-07 diets, respectively.