ABSTRACT
In the past three decades, the prevalence of type-2 diabetes has arisen dramatically in countries of all income levels. A novel, most effective nanotechnology-based strategy may reduce the prevalence of diabetes. Recently, the shell-crosslinked polysaccharide-based micellar nanocarriers (MNCs) have shown great promise in terms of stability, controlled drug release, and improved in vivo performance. In this study, heptyl carboxymethyl guar gum was synthesized and characterized by ATR-FTIR, 1HNMR spectroscopy, surface charge, critical micelle concentration (23.9 µg/mL), and cytotoxicity analysis. Box-Behnken design was used to optimize the diameter, zeta potential, drug entrapment efficiency (DEE), and drug release characteristics of poly (allylamine)-crosslinked MNCs containing canagliflozin. The optimized MNCs revealed spherical morphology under TEM and had 149.3 nm diameter (PDI 21.2 %), +53.8 mV zeta potential, and 84 % DEE. The MNCs released about 63 % of the drug in 12 h under varying pH of the simulated gastrointestinal fluid. DSC and x-ray analyses suggested amorphous dispersion of drugs in the MNCs. CAM assay demonstrated the biocompatibility of the MNCs. The MNCs showed hemolysis of <1 %, 85 % mucin adsorption, and stability over three months. The MNCs demonstrated excellent anti-diabetic efficacy in streptozotocin-nicotinamide-induced diabetic rats, continuously lowering blood glucose levels up to 12 h.
Subject(s)
Canagliflozin , Diabetes Mellitus, Experimental , Diabetes Mellitus, Type 2 , Drug Carriers , Galactose , Mannans , Polyamines , Animals , Galactose/chemistry , Galactose/analogs & derivatives , Mannans/chemistry , Mannans/pharmacology , Rats , Drug Carriers/chemistry , Diabetes Mellitus, Type 2/drug therapy , Polyamines/chemistry , Diabetes Mellitus, Experimental/drug therapy , Canagliflozin/chemistry , Canagliflozin/pharmacology , Drug Liberation , Nanoparticles/chemistry , Male , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Blood Glucose/drug effects , Galactans/chemistry , Galactans/pharmacology , Plant Gums/chemistryABSTRACT
A stable Madhuca indica oil-in-water nanoemulsion (99-210 nm, zeta potential: > - 30 mV) was produced employing Tween 20 (surfactant) and Transcutol P (co-surfactant) (3:1). The nanoemulsion (oil: Smix = 3:7, 5:5, and 7:3) were subsequently incorporated into oxcarbazepine-loaded carboxymethylxanthan gum (DS = 1.23) dispersion. The hydrogel microspheres were formed using the ionic gelation process. Higher oil concentration had a considerable impact on particle size, drug entrapment efficiency, and buoyancy. The maximum 92 % drug entrapment efficiency was achieved with the microspheres having oil: Smix ratio 5:5. FESEM study revealed that the microspheres were spherical in shape and had an orange peel-like surface roughness. FTIR analysis revealed a hydrogen bonding interaction between drug and polymer. Thermal and x-ray examinations revealed the transformation of crystalline oxcarbazepine into an amorphous form. The microspheres had a buoyancy period of 7.5 h with corresponding release of around 83 % drug in 8 h in simulated stomach fluid, governed by supercase-II transport mechanism. In vivo neurobehavioral studies on PTZ-induced rats demonstrated that the microspheres outperformed drug suspension in terms of rotarod retention, number of crossings, and rearing activity in open field. Thus, Madhuca indica oil-in-water nanoemulsion-entrapped carboxymethyl xanthan gum microspheres appeared to be useful for monitoring oxcarbazepine release and managing epileptic seizures.
Subject(s)
Mannans , Microspheres , Animals , Rats , Mannans/chemistry , Hydrogels/chemistry , Particle Size , Epilepsy/drug therapy , Male , Drug Carriers/chemistry , Emulsions , Seizures/drug therapy , Drug Liberation , Plant Oils/chemistry , Plant Oils/pharmacology , Anticonvulsants/chemistry , Anticonvulsants/pharmacology , Galactose/analogs & derivativesABSTRACT
Natural polysaccharides are being studied for their biocompatibility, biodegradability, low toxicity, and low cost in the fabrication of various hydrogel devices. However, due to their insufficient physicochemical and mechanical qualities, polysaccharide hydrogels alone are not acceptable for biological applications. Various synthetic crosslinkers have been tested to overcome the drawbacks of standalone polysaccharide hydrogels; however, the presence of toxic residual crosslinkers, the generation of toxic by-products following biodegradation, and the requirement of toxic organic solvents for processing pose challenges in achieving the desired non-toxic biomaterials. Natural crosslinkers such as citric acid, tannic acid, vanillin, gallic acid, ferulic acid, proanthocyanidins, phytic acid, squaric acid, and epigallocatechin have been used to generate polysaccharide-based hydrogels in recent years. Various polysaccharides, including cellulose, alginate, pectin, hyaluronic acid, and chitosan, have been hydrogelized and investigated for their potential in drug delivery and tissue engineering applications using natural crosslinkers. We attempted to provide an overview of the synthesis of polysaccharide-based hydrogel systems (films, complex nanoparticles, microspheres, and porous scaffolds) based on green crosslinkers, as well as a description of the mechanism of crosslinking and properties with a special emphasis on drug delivery, and tissue engineering applications.
Subject(s)
Hydrogels , Tissue Engineering , Hydrogels/chemistry , Polysaccharides/chemistry , Drug Delivery SystemsABSTRACT
Natural polysaccharides have been widely exploited in drug delivery and tissue engineering research. They exhibit excellent biocompatibility and fewer adverse effects; however, it is challenging to assess their bioactivities to that of manufactured synthetics because of their intrinsic physicochemical characteristics. Studies showed that the carboxymethylation of polysaccharides considerably increases the aqueous solubility and bioactivities of inherent polysaccharides and offers structural diversity, but it also has some limitations that can be resolved by derivatization or the grafting of carboxymethylated gums. The swelling ratio, flocculation capacity, viscosity, partition coefficient, metal absorption properties, and thermosensitivity of natural polysaccharides have been improved as a result of these changes. In order to create better and functionally enhanced polysaccharides, researchers have modified the structures and properties of carboxymethylated gums. This review summarizes the various ways of modifying carboxymethylated gums, explores the impact that molecular modifications have on their physicochemical characteristics and bioactivities, and sheds light on various applications for the derivatives of carboxymethylated polysaccharides.
ABSTRACT
Diverse properties of natural gums have made them quite useful for various pharmaceutical applications. However, they suffer from various problems, including unregulated hydration rates, microbial degradation, and decline in viscosity during warehousing. Among various chemical procedures for modification of gums, carboxymethylation has been widely studied due to its simplicity and efficiency. Despite the availability of numerous research articles on natural gums and their uses, a comprehensive review on carboxymethylation of natural gums and their applications in the pharmaceutical and other biomedical fields is not published until now. This review outlines the classification of gums and their derivatization methods. Further, we have discussed various techniques of carboxymethylation, process of determination of degree of substitution, and functionalization pattern of substituted gums. Detailed information about the application of carboxymethyl gums as drug delivery carriers has been described. The article also gives a brief account on tissue engineering and cell delivery potential of carboxymethylated gums.
Subject(s)
Drug Carriers , Excipients , Chemical Phenomena , Drug Carriers/chemistry , Drug Delivery Systems , Excipients/chemistry , Plant Gums/chemistry , ViscosityABSTRACT
Herein, the repaglinide-loaded hydrogel particles of carboxyethyl xanthan gum (CEXG) and carboxymethyl xanthan gum (CMXG) were fabricated, and controlled drug delivery performance was assessed. The XG derivatives were characterized by FTIR analyses, degree of substitution, and cytotoxicity assay. CEXG: CMXG (1:2) hydrogel particles had maximum drug entrapment efficiency of 92%. The hydrogel particles swelled a maximum of about 2.25 times in phosphate buffer (pH 6.8) than that in acidic medium (pH 1.2) in 2 h. The particles discharged 97% drug in simulated gastrointestinal pH in 4 h. The acetylation of hydrogel particles reduced the drug entrapment efficiency to 78%; however, it extended drug release up to 8 h, obeying anomalous diffusion. DSC and X-ray diffraction analyses suggested amorphous dispersion of repaglinide after entrapment. Preclinically, the acetylated hydrogels caused a maximum 52.8% reduction in blood glucose level and effectively lowered blood glucose up to 8 h. Hence, the acetylated CEXG: CMXG hydrogel particles could help control diabetes.
Subject(s)
Diabetes Mellitus , Hydrogels , Blood Glucose , Carbamates , Humans , Hydrogels/chemistry , Piperidines , Polysaccharides, Bacterial/chemistryABSTRACT
Xanthan gum (XG) possesses numerous hydroxyl groups, which are the focal points for graft copolymerization of synthetic monomers. A detailed mechanism of graft copolymerization is of utmost importance in obtaining new materials with desirable attributes. The physicochemical, thermal, and morphological changes gained after graft copolymerization is also described. The graft copolymerization can further improve adsorption efficiency of toxic heavy metals and synthetic dyes from wastewater or industrial effluents. The swelling and pH-sensitivity of graft copolymer are attractive features for the purpose of controlled drug delivery. Despite a plethora of reports, comprehensive reviews on XG-based graft copolymers and their potential applications are scarce. Hence, this review undertakes detailed discussion on the synthesis of XG-based graft copolymer, their properties and potential application in drug delivery and wastewater treatment, which would be interesting for the readers and budding scientists to progress further with polysaccharide research and explore new materials for the intended purposes.
Subject(s)
Drug Delivery Systems/methods , Polysaccharides, Bacterial/chemistry , Water Purification/methods , Biopolymers/chemistry , Humans , Pharmaceutical Preparations/chemistry , Polymerization , Wastewater/chemistryABSTRACT
Reduction of ice masses concerning global warming is significantly changing geomorphology in high mountains. Formation of supraglacial lakes is one of such essential indications. Therefore, in the present study, we attempted to understand regional morphodynamics of supraglacial lakes, distributed in 17 glaciers within the Everest Himalaya. An average of 0.08 km2/yr lake expansion rate was noticed during the studied year. Decadal (2010-2019) lake morphodynamic study using high resolution satellite images revealed that only 161 out of total 2424 lakes were static, and mostly concentrated at the lower part of the ablation area with an alarming rate of surface area increase. We also found appearance of new cluster of lakes at higher elevations. We collected here statistical evidences of regional morphodynamics and key controlling factors to stabilize lakes. The parameters, viz., spatio-temporal distribution of lakes, their domain wise variation, multi-temporal (Seasonal to long-term) changes, lake density, and stability index were estimated and mapped. Finally, we concluded that new lake formations at higher elevation were triggered by gradual increase in temperature, decrease in glacier surface velocity, slope and ice thickness. The feature selection techniques indicated ice thickness as prior controlling factor followed by the surface velocity and slope to stabilize lakes at the lower part of ablation.
ABSTRACT
Nanotheranostics, an approach of combining both diagnosis and therapy, is one of the latest advances in cancer therapy particularly. Nanocarriers designed and derived from inorganic materials such as like gold nanoparticles, silica nanoparticles, magnetic nanoparticles and carbon nanotubes have been explored for tremendous applications in this area. Similarly, nanoparticles composed of some organic material alone or in combination with inorganic nano-cargos have been developed pre-clinically and possess excellent features desired. Photothermal therapy, MRI, simultaneous imaging and delivery, and combination chemotherapy with a diagnosis are a few of the known methods exploring cancer therapy and detection at organ/tissue/molecular/sub-cellular level. This review comprises an overview of the recent reports meant for nano theranostics purposes. Targeted cancer nanotheranostics have been included for understating tumor micro-environment or cell-specific targeting approach employed. A brief account of various strategies is also included for the readers highlighting the mechanism of cancer therapy.
Subject(s)
Metal Nanoparticles , Nanoparticles , Nanotubes, Carbon , Neoplasms , Gold , Humans , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Theranostic Nanomedicine , Tumor MicroenvironmentABSTRACT
Galactomannans are naturally occurring biocompatible and biodegradable nonionic polysaccharides comprised of mannose and galactose residues. They are under investigation for the design of various drug delivery carriers such as matrix tablets, microparticles, nanoparticles/nanocomposites, polymeric micelles, hydrogels, as well as pharmaceutical excipients. Amongst galactomannans, guar gum, locust bean gum, and fenugreek gum are the biomaterials mostly investigated for their potential utility as nanocarriers for various purposes, either in their native or modified forms. The galactomannan-based nanomaterials have been fabricated by adopting various strategies. These galactomannan nanomaterials have been tested for oral vaccination, oral insulin delivery, cancer cell & macrophage targeting, controlled drug delivery, heavy metal extraction and wound dressing applications. The galactomannan has attracted the attention of researchers as reducing agents for the green synthesis of metal nanoparticles as well. These nanometals have shown improved antimicrobial, antioxidant and anticancer activities. In vitro toxicity of the nanomaterials is also assessed in some instances. Others such as cassia gum, tara gum, Delonix, Leucaena leucocephala, Punica granatum galactomannans are amongst the least studied materials for biological applications. This review describes various strategies adopted for the synthesis of galactomannan-based nanomaterials, their properties and applications, especially in the field of drug delivery.
Subject(s)
Biocompatible Materials/chemistry , Mannans/chemistry , Nanostructures/chemistry , Polysaccharides/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/therapeutic use , Drug Delivery Systems , Galactans/chemical synthesis , Galactans/chemistry , Galactose/analogs & derivatives , Humans , Mannans/chemical synthesis , Mannans/therapeutic use , Plant Gums/chemical synthesis , Plant Gums/chemistry , Polysaccharides/chemical synthesis , Polysaccharides/therapeutic use , Trigonella/chemistryABSTRACT
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.
Subject(s)
Hypertension/drug therapy , Karaya Gum/chemistry , Diffusion , Drug Carriers/chemistry , Drug Liberation , Hypertension/metabolism , Polymers/chemistry , SolubilityABSTRACT
Natural polysaccharides are well known for their biocompatibility, non-toxicity and biodegradability. These properties are also inherent to xanthan gum (XG), a microbial polysaccharide. This biomaterial has been extensively investigated as matrices for tablets, nanoparticles, microparticles, hydrogels, buccal/transdermal patches, tissue engineering scaffolds with different degrees of success. However, the native XG has its own limitations with regards to its susceptibility to microbial contamination, unusable viscosity, poor thermal and mechanical stability, and inadequate water solubility. Chemical modification can circumvent these limitations and tailor the properties of virgin XG to fulfill the unmet needs of drug delivery, tissue engineering, oil drilling and other applications. This review illustrates the process of chemical modification and/crosslinking of XG via etherification, esterification, acetalation, amidation, and oxidation. This review further describes the tailor-made properties of novel XG derivatives and their potential application in diverse fields. The physicomechanical modification and its impact on the properties of XG are also discussed. Overall, the recent developments on XG derivatives are very promising to progress further with polysaccharide research.
ABSTRACT
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.
Subject(s)
Bosentan/administration & dosage , Drug Delivery Systems , Karaya Gum/chemistry , Nanogels/chemistry , Polyethylene Glycols/chemistry , Polyethyleneimine/chemistry , Animals , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/pharmacology , Antihypertensive Agents/therapeutic use , Bosentan/pharmacology , Bosentan/therapeutic use , Calorimetry, Differential Scanning , Disease Models, Animal , Drug Liberation , Hypertension/drug therapy , Karaya Gum/chemical synthesis , Male , Mice , Rats, Wistar , Spectroscopy, Fourier Transform Infrared , X-Ray DiffractionABSTRACT
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.
Subject(s)
Antihypertensive Agents/chemistry , Drug Carriers/chemistry , Galactans/chemistry , Hydrogels/chemistry , Hypertension/drug therapy , Karaya Gum/chemistry , Mannans/chemistry , Plant Gums/chemistry , Animals , Antihypertensive Agents/therapeutic use , Carvedilol/chemistry , Carvedilol/therapeutic use , Drug Design , Drug Liberation , Hydrogen-Ion Concentration , Male , Mice , Particle Size , ViscosityABSTRACT
Ichnocarpus frutescens, a climber plant, is distributed all over India. As its different parts are used as anti-inflammatory agent, so we re-investigated the roots to isolate compounds and evaluate its biological efficacy. Also, in-silico molecular docking was carried out to elucidate the structure activity relationship (SAR) of isolated compounds toward identifies the drug target enzyme with validation, which was further supported by anti-inflammatory in-vitro and in-vivo experimental models. The compounds have been undertaken mainly to investigate the anti-inflammatory and analgesic efficacy along with molecular docking investigation followed by anti-proteinase, anti-denaturation and cyclooxygenase (COX) inhibition studies. Inflammatory cytokines like TNF-α and IL-6 were assayed from lipopolysaccharides (LPS) and Concavallin (CON A) stimulated human PBMC derived macrophages by Enyme linked immune sorbent assay (ELISA) method. The purity index of the lead compound was determined by HPLC. The compounds were illustrated as 2-hydroxy tricosanoic acid (1), stigmasterol glucoside (2), stigmasterol (3), ß-sitosterol (4) and ß-sitosterol glucoside (5). The test molecules showed significant anti-denaturation, anti-proteinase and analgesic effect validated with docking study. Compounds exhibited anti-inflammatory and pain killing action due to dexamethasone like phytosterol property. Promising anti-denaturation and anti-proteinase activity offered by the compound 5, may hold its promise to fight against arthritis by rejuvenating the osteoblast cells and destroying the bone-resorpting complex of hydrated protein, bone minerals by secreting the acid and an enzyme collagenase along with pain management. The lead bioactive compound i.e. ß-sitosterol glucoside (compound 5) demonstrated considerable anti-inflammatory activity showing more than 90% protection against the inflammatory cytokines at 50⯵M dose. The anti-denaturation and COX-2 inhibition shown by the compound 5 was also noteworthy with the significant IC50 (ranging from 0.25 to 2.56⯵M) that also supporting its future promise for developing as anti-inflammatory agent. Since the most bio-active compound (5) elicit promising acute anti-inflammatory action and peripheral anti-nociceptive pain killing action with a significant ED50 dose of 3.95 & 2.84â¯mg/kg i.p. respectively in the in-vivo animal model. It could suggest its potentiality as a good in-vivo bio available agent to be an emerging anti-inflammatory drug regimen scaffold in the future. It also establishes significant in-vitro and in-vivo result co-relation. Therefore, the compound 5 could be believed as a potent lead for designing anti-inflammatory, anti-arthritic drug or pain killer without showing any untoward effect.
Subject(s)
Apocynaceae/chemistry , Inflammation/drug therapy , Nociceptive Pain/drug therapy , Steroids/administration & dosage , Analgesics/pharmacology , Anti-Inflammatory Agents/pharmacology , Cytokines/metabolism , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/isolation & purification , Glucosides/chemistry , Glucosides/isolation & purification , Humans , Inflammation/pathology , Interleukin-6/genetics , Leukocytes, Mononuclear/drug effects , Lipopolysaccharides/chemistry , Macrophages/drug effects , Molecular Docking Simulation , Nociceptive Pain/pathology , Pain Perception/drug effects , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Sitosterols/chemistry , Sitosterols/isolation & purification , Steroids/chemistry , Steroids/isolation & purification , Stigmasterol/analogs & derivatives , Stigmasterol/chemistry , Stigmasterol/isolation & purification , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Olive oil-entrapped diethanolamine-modified high-methoxyl pectin (DMP)-gellan gum (GG)-bionanofiller composites were developed for controlled intragastric delivery of metformin HCl (MFM). DMP had a degree of amidation of 48.7% and was characterized further by FTIR, XRD and DSC analyses. MFM-loaded composites were subsequently accomplished by green synthesis via ionotropic gelation technique using zinc acetate as cross-linker. The thermal, X-ray and infrared analyses suggested an environment in the composites compatible with the drug, except certain degree of attenuation in drug's crystallinity. Scanning electron microscopy revealed almost spherical shape of the composites. Depending upon the mass ratios of GG:DMP, types of nanofiller (neusilin/bentonite/Florite) and oil inclusion, the composites exhibited variable drug encapsulation efficiency (DEE, 50-85%) and extended drug release behaviours (Q8h, 69-94%) in acetate buffer (pHâ¯4.5). The optimized oil-entrapped Florite R NF/GG: DMP (1:1) composites eluted MFM via case-II transport mechanism and its drug release data was best fitted in zero-order kinetic model. The optimized formulation demonstrated excellent gastroretentive properties and substantial hypoglycemic effect in streptozotocin-induced diabetic rats. These novel hybrid matrices were thus found suitable for controlled intragastric delivery of MFM for the management of type 2 diabetes.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Drug Delivery Systems , Metformin/administration & dosage , Polysaccharides, Bacterial/administration & dosage , Animals , Diabetes Mellitus, Experimental/pathology , Drug Liberation , Ethanolamines/administration & dosage , Ethanolamines/chemistry , Humans , Metformin/chemistry , Microspheres , Olive Oil/administration & dosage , Olive Oil/chemistry , Pectins/chemistry , Polysaccharides, Bacterial/chemistry , RatsABSTRACT
PURPOSE: The application of betulinic acid (B), a potent antineoplastic agent, is limited due to poor bioavailability, short plasma half-life and inappropriate tissue distribution. Thus, we aimed to prepare novel 50:50 poly(lactic-co-glycolic acid) (PLGA)-loaded B nanoparticles (BNP) and to compare its anti-hepatocellular carcinoma (HCC) activity with parent B. METHODS: BNP were synthesized and characterized using different methods such as scanning electron microscopy (SEM), fourier-transform infrared (FTIR) spectrometry and particle size analyses. Particle size of BNP was optimized through the application of the stabilizer, polyvinyl alcohol (PVA). The anti-HCC response was evaluated through in vitro cell line study using Hep-G2 cells, confocal microscopy, in vivo oral pharmacokinetics and animal studies. Further, quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was conducted to observe the changes in the expression of specific genes. RESULTS: Particle size of BNP was optimized through the application of the stabilizer, polyvinyl alcohol. Physicochemical characterization exhibited particle size of 257.1 nm with zeta potential -0.170 mV (optimized batch B, BNP). SEM and FTIR analyses of BNP showed that cylindrical particles of B converted to spherical particles in BNP and there were no interaction between B and used polymers. The release study of optimized BNP was highest (≥80%) than any other formulation. Later, in vitro cell culture analysis using Hep-G2 cells and confocal microscopy studies revealed that BNP had the highest inhibition and penetration properties than parent B. Oral pharmacokinetics studies using albino Wistar rats at single 100 mg dose again exhibited BNP had the higher 50% of plasma concentration (t1/2), a higher maximum plasma concentration (Cmax) and took longer to reach the maximum plasma concentration (Tmax) than parent B. Next, our in vivo study using nitrosodiethyl amine (NDEA)-induced HCC model documented BNP decreased in number of nodules, restored body weight, oxidative stress parameters, liver marker enzymes and histological architecture than parent B. Lastly, qRT-PCR studies further demonstrated that anti-HCC properties of BNP may be due to over expression of antiapoptotic caspases i.e., caspase 3 and 8. CONCLUSION: The prepared BNP showed a better therapeutic response against HCC and could be attributed as future candidate molecule for HCC treatment.
Subject(s)
Lactic Acid/chemistry , Liver Neoplasms/drug therapy , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Triterpenes/therapeutic use , Administration, Oral , Animals , Antineoplastic Agents/blood , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Carcinoma, Hepatocellular/drug therapy , Cell Proliferation/drug effects , Chromatography, High Pressure Liquid , Drug Carriers/chemistry , Drug Liberation , Half-Life , Hep G2 Cells , Humans , Inflammation Mediators/metabolism , Kinetics , Liver/drug effects , Liver/pathology , Liver/physiopathology , Liver Neoplasms/pathology , Liver Neoplasms/ultrastructure , Male , Nanoparticles/ultrastructure , Oxidative Stress/drug effects , Particle Size , Pentacyclic Triterpenes , Polylactic Acid-Polyglycolic Acid Copolymer , Rats, Wistar , Spectroscopy, Fourier Transform Infrared , Static Electricity , Triterpenes/blood , Triterpenes/chemistry , Triterpenes/pharmacokinetics , Betulinic AcidABSTRACT
Novel carboxymethyl fenugreek galactomannan (CFG)-gellan gum (GG)-calcium silicate (CS) composite beads were developed for controlled glimepiride (GLI) delivery. CFG having degree of carboxymethylation of 0.71 was synthesized and characterized by FTIR, DSC and XRD analyses. Subsequently, GLI-loaded hybrids were accomplished by ionotropic gelation technique employing Ca+2/Zn+2/Al+3 ions as cross-linkers. All the formulations demonstrated excellent drug encapsulation efficiency (DEE, 48-97%) and sustained drug release behaviour (Q8h, 62-94%). These quality attributes were remarkably influenced by polymer-blend (GG:CFG) ratios, cross-linker types and CS inclusion. The drug release profile of the optimized formulation (F-6) was best fitted in zero-order model with anomalous diffusion driven mechanism. It also conferred excellent ex vivo mucoadhesive property and considerable hypoglycemic effect in streptozotocin-induced diabetic rats. Furthermore, the beads were characterized for drug-excipients compatibility, drug crystallinity, thermal behaviour and surface morphology. Thus, the developed hybrid matrices are appropriate for controlled delivery of GLI for Type 2 diabetes management.
Subject(s)
Delayed-Action Preparations/chemical synthesis , Diabetes Mellitus, Experimental/drug therapy , Drug Carriers , Hypoglycemic Agents/pharmacokinetics , Sulfonylurea Compounds/pharmacokinetics , Trigonella/chemistry , Animals , Calcium Compounds/chemistry , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Drug Compounding/methods , Drug Liberation , Galactose/analogs & derivatives , Hypoglycemic Agents/pharmacology , Mannans/chemistry , Polysaccharides, Bacterial/chemistry , Rats , Silicates/chemistry , Streptozocin , Sulfonylurea Compounds/pharmacologyABSTRACT
Gum Ghatti (GG) is a water soluble complex polysaccharide obtained from Anogeissus latifolia. Due to its non toxic and excellent emulsifying characteristics, it was widely used in different pharmaceutical preparations. Currently another facet was explored for its utility as release retardant polymer in oral controlled drug delivery system. As GG solely was incapable of forming microspheres therefore modification of GG to Sodium carboxymethyl (NaCMGG) derivative was done by carboxymethylation process and its gel forming capacity was explored by the use of trivalent cation (Aluminium chloride) which results into complete microbead system in a complete aqueous environment for controlled delivery of Ropinirole Hydrochloride (RHCl). Rheological property of NaCMGG showed pseudoplastic shear thinning behavior. Spherical shape of bead was observed under scanning electron microscope. Depending upon the formulation variables, Drug entrapment efficiency (DEE) varies from 47.66±3.51 % to 71.4±2.65%., and 80 to 90% drug was released in 6h in pH 6.8 phosphate buffer. Drug release was governed by both fickian diffusion and polymer relaxation simultaneously. Compatible environment for drug entrapment was established by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). Thus the modified derivative NaCMGG could be a promising polymer in biomedical application.
Subject(s)
Ethers/chemistry , Hydrogels/chemistry , Indoles/administration & dosage , Indoles/chemistry , Plant Gums/chemistry , Administration, Oral , Delayed-Action Preparations , Drug Liberation , KineticsABSTRACT
In this study, gelatin and carboxymethyl tamarind gum (CTG) were chemically cross-linked to control the delivery of aceclofenac from their interpenetrating network (IPNs). Infrared spectra, thermal and X-ray data supported that drug and polymer was compatible in the composite hydrogels. Irregularly shaped IPN microstructures were seen under field emission scanning electron microscope (FE-SEM). IPN system was capable of entrapping about 96% of the drug fed. CTG in IPN structures suppressed the drug release rate in HCl solution (pH1.2); however extended the same in phosphate buffer solution (pH6.8). The drug release was controlled by polymer chain relaxation/swelling and simple diffusion in vitro. The anti-inflammatory activity of drug-loaded biocomposites lasted over 7h in albino rats, thus suggesting their potential as an anti-inflammatory therapeutics.