Curcumin coating: a novel solution to mitigate inherent carbon nanotube toxicity.

Multi-walled Carbon Nanotubes (MWCNTs) are inert structures with high aspect ratios that are widely used as vehicles for targeted drug delivery in cancer and many other diseases. They are largely non-toxic in nature however, when cells are exposed to these nanotubes for prolonged durations or at high concentrations, they show certain adverse effects. These include cytotoxicity, inflammation, generation of oxidative stress, and genotoxicity among others. To combat such adverse effects, various moieties can be attached to the surface of these nanotubes. Curcumin is a known anti-inflammatory, antioxidant and cytoprotective compound derived from a medicinal plant called Curcuma longa. In this study, we have synthesized and characterized Curcumin coated-lysine functionalized MWCNTs and further evaluated the cytoprotective, anti-inflammatory, antioxidant and antiapoptotic effect of Curcumin coating on the surface of MWCNTs. The results show a significant decrease in the level of inflammatory molecules like IL-6, IL-8, IL-1ß, TNFα and NFκB in cells exposed to Curcumin-coated MWCNTs as compared to the uncoated ones at both transcript and protein levels. Further, compared to the uncoated samples, there is a reduction in ROS production and upregulation of antioxidant enzyme-Catalase in the cells treated with Curcumin-coated MWCNTs. Curcumin coating also helped in recovery of mitochondrial membrane potential in the cells exposed to MWCNTs. Lastly, cells exposed to Curcumin-coated MWCNTs showed reduced cell death as compared to the ones exposed to uncoated MWCNTs. Our findings suggest that coating of Curcumin on the surface of MWCNTs reduces its ability to cause inflammation, oxidative stress, and cell death.

Design, synthesis, and anticancer activity of some novel 1H-benzo[d]imidazole-5-carboxamide derivatives as fatty acid synthase inhibitors.

Multiple malignancies exhibit aberrant FASN expression, associated with enhanced de novo lipogenesis to meet the metabolic demands of rapidly proliferating tumour cells. Furthermore, elevated FASN expression has been linked to tumour aggressiveness and poor prognosis in a variety of malignant tumours, making FASN is an attractive target for anticancer drug discovery. Herein, we report the de novo design and synthesis of (2-(2-hydroxyphenyl)-1H-benzo[d]imidazol-5-yl)(piperazin-1-yl)methanone derivatives as novel FASN inhibitors with potential therapeutic applications in breast and colorectal cancers. Twelve (2-(2-hydroxyphenyl)-1H-benzo[d]imidazol-5-yl)(piperazin-1-yl)methanone derivatives (CTL) were synthesized and evaluated for FASN inhibition and cytotoxicity against colon cancer (HCT-116, Caco-2 cell lines), breast cancer (MCF-7 cell line) and normal cell line (HEK-293). Compounds CTL-06 and CTL-12 were chosen as the most promising lead molecules based on FASN inhibition and selective cytotoxicity profiles against colon and breast cancer cell lines. Compounds CTL-06 and CTL-12 demonstrate promising FASN inhibitory activity at IC50 of 3 ± 0.25 µM and 2.5 ± 0.25 µM when compared to the FASN inhibitor orlistat, which has an IC50 of 13.5 ± 1.0 µM. Mechanistic investigations on HCT-116 revealed that CTL-06 and CTL-12 treatment led to cell cycle arrest in Sub-G1/S phase along with apoptosis induction. Western blot studies indicated that CTL-06 and CTL-12 inhibited FASN expression in a dose-dependent manner. CTL-06 and CTL-12 treatment of HCT-116 cells enhanced caspase-9 expression in a dose-dependent manner, while upregulating proapoptotic marker Bax and downregulating antiapoptotic Bcl-xL. Molecular docking experiments of CTL-06 and CTL-12 with FASN enzyme revealed the mode of binding of these analogues in the KR domain of the enzyme.

Antiproliferative Efficacy of N-(3-chloro-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine, DW-8, in Colon Cancer Cells Is Mediated by Intrinsic Apoptosis.

A novel series of 4-anilinoquinazoline analogues, DW (1-10), were evaluated for anticancer efficacy in human breast cancer (BT-20) and human colorectal cancer (CRC) cell lines (HCT116, HT29, and SW620). The compound, DW-8, had the highest anticancer efficacy and selectivity in the colorectal cancer cell lines, HCT116, HT29, and SW620, with IC50 values of 8.50 ± 2.53 µM, 5.80 ± 0.92 µM, and 6.15 ± 0.37 µM, respectively, compared to the non-cancerous colon cell line, CRL1459, with an IC50 of 14.05 ± 0.37 µM. The selectivity index of DW-8 was >2-fold in colon cancer cells incubated with vehicle. We further determined the mechanisms of cell death induced by DW-8 in SW620 CRC cancer cells. DW-8 (10 and 30 µM) induced apoptosis by (1) producing cell cycle arrest at the G2 phase; (2) activating the intrinsic apoptotic pathway, as indicated by the activation of caspase-9 and the executioner caspases-3 and 7; (3) nuclear fragmentation and (4) increasing the levels of reactive oxygen species (ROS). Overall, our results suggest that DW-8 may represent a suitable lead for developing novel compounds to treat CRC.

A Novel Dialkylamino-Functionalized Chalcone, DML6, Inhibits Cervical Cancer Cell Proliferation, In Vitro, via Induction of Oxidative Stress, Intrinsic Apoptosis and Mitotic Catastrophe.

In this study, we designed, synthesized and evaluated, in vitro, novel chalcone analogs containing dialkylamino pharmacophores in the cervical cancer cell line, OV2008. The compound, DML6 was selective and significantly decreased the proliferation of OV2008 and HeLa cells in sub-micromolar concentrations, compared to prostate, lung, colon, breast or human embryonic kidney cell line (HEK293). DML6, at 5 µM, arrested the OV2008 cells in the G2 phase. Furthermore, DML6, at 5 µM, increased the levels of reactive oxygen species and induced a collapse in the mitochondrial membrane potential, compared to OV2008 cells incubated with a vehicle. DML6, at 5 µM, induced intrinsic apoptosis by significantly (1) increasing the levels of the pro-apoptotic proteins, Bak and Bax, and (2) decreasing the levels of l the anti-apoptotic protein, Bcl-2, compared to cell incubated with a vehicle. Furthermore, DML6, at 5 and 20 µM, induced the cleavage of caspase-9, followed by subsequent cleavage of the executioner caspases, caspase-3 and caspase-7, which produced OV2008 cell death. Overall, our data suggest that DML6 is an apoptosis-inducing compound that should undergo further evaluation as a potential treatment for cervical cancer.

Design, synthesis and biological evaluation of some tetrazole acetamide derivatives as novel non-carboxylic PTP1B inhibitors.

A series of ten N-(3-(1H-tetrazole-5-yl)phenyl)acetamide derivatives (NM-07 to NM-16) designed from a lead molecule identified previously in our laboratory were synthesized and evaluated for protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Among the synthesized molecules, NM-14, a 5-Cl substituted benzothiazole analogue elicited significant PTP1B inhibition with an IC50 of 1.88 µM against reference standard suramin (IC50 ≥ 10 µM). Furthermore, this molecule also showed good in vivo antidiabetic activity which was comparable to that of standard antidiabetic drugs metformin and glimepiride. Overall, the results of the study clearly reveal that the reported tetrazole derivatives especially NM-14 are valuable prototypes for the development of novel non-carboxylic inhibitors of PTP1B with antidiabetic potential.

lH-Pyrazolo[3,4-b]quinolin-3-amine derivatives inhibit growth of colon cancer cells via apoptosis and sub G1 cell cycle arrest.

A series of lH-pyrazolo[3,4-b]quinolin-3-amine derivatives were synthesized and evaluated for anticancer efficacy in a panel of ten cancer cell lines, including breast (MDAMB-231 and MCF-7), colon (HCT-116, HCT-15, HT-29 and LOVO), prostate (DU-145 and PC3), brain (LN-229), ovarian (A2780), and human embryonic kidney (HEK293) cells, a non-cancerous cell line. Among the eight derivatives screened, compound QTZ05 had the most potent and selective antitumor efficacy in the four colon cancer cell lines, with IC50 values ranging from 2.3 to 10.2 µM. Furthermore, QTZ05 inhibited colony formation in HCT-116 cells in a concentration-dependent manner. Cell cycle analysis data indicated that QTZ05 caused an arrest in the sub G1 cell cycle in HCT-116 cells. QTZ05 induced apoptosis in HCT-116 cells in a concentration-dependent manner that was characterized by chromatin condensation and increase in the fluorescence of fluorochrome-conjugated Annexin V. The findings from our study suggest that QTZ05 may be a valuable prototype for the development of chemotherapeutics targeting apoptotic pathways in colorectal cancer cells.

Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation.

Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC50 value of 4.48 µM. Docking studies with NM-03 revealed the key interactions with desired amino acids in the binding site of PTP1B. Furthermore, compound NM-03 also elicited good in vivo activity. Taken together, the results of this study establish N-(3-(1H-tetrazole-5-yl)phenyl)-2-(benzo[d]oxazol-2-ylthio)acetamide (NM-03) as a valuable lead molecule with great potential for PTP1B inhibitor development targeting diabetes.

Molecular dynamic simulations and structure-based pharmacophore development for farnesyltransferase inhibitors discovery.

Farnesyltransferase is one of the enzyme targets for the development of drugs for diseases, including cancer, malaria, progeria, etc. In the present study, the structure-based pharmacophore models have been developed from five complex structures (1LD7, 1NI1, 2IEJ, 2ZIR and 2ZIS) obtained from the protein data bank. Initially, molecular dynamic (MD) simulations were performed for the complexes for 10 ns using AMBER 12 software. The conformers of the complexes (75) generated from the equilibrated protein were undergone protein-ligand interaction fingerprint (PLIF) analysis. The results showed that some important residues, such as LeuB96, TrpB102, TrpB106, ArgB202, TyrB300, AspB359 and TyrB361, are predominantly present in most of the complexes for interactions. These residues form side chain acceptor and surface (hydrophobic or π-π) kind of interactions with the ligands present in the complexes. The structure-based pharmacophore models were generated from the fingerprint bits obtained from PLIF analysis. The pharmacophore models have 3-4 pharmacophore contours consist of acceptor and metal ligation (Acc & ML), hydrophobic (HydA) and extended acceptor (Acc2) features with the radius ranging between 1-3 Å for Acc & ML and 1-2 Å for HydA. The excluded volumes of the pharmacophore contours radius are between 1-2 Å. Further, the distance between the interacting groups, root mean square deviation (RMSD), root mean square fluctuation (RMSF) and radial distribution function (RDF) analysis were performed for the MD-simulated proteins using PTRAJ module. The generated pharmacophore models were used to screen a set of natural compounds and database compounds to select significant HITs. We conclude that the developed pharmacophore model can be a significant model for the identification of HITs as FTase inhibitors.

Predictive QSAR models development and validation for human ether-a-go-go related gene (hERG) blockers using newer tools.

In the present computational analysis, pharmacophore-based active conformer selection method was used to derive active conformers for the physicochemical descriptors calculation. The significant regression models were validated using different validation methods, which provided significant Q(2) values. The distance-based approaches were also used to analyze the discriminant property of the molecules contributed in the models. The Mahalanobis distance (MD) values obtained from these studies revealed that the compounds with very high and very low acting human ether-a-go-go-related gene blockers possessed high MD values, while the predicted activity of those compounds exhibited less residual errors. The results obtained in the studies suggest that the distance-based approaches can be used to validate the quantitative structure-activity relationship models significantly. The descriptors contributed in the models explain that the flexibility of the bonds connected to the aromatic rings or non-polar region of the molecules make π-π interaction with the aromatic residues of the protein.

Role of magnetic resonance imaging cephalometry in obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is one of the most common public health problems in adults. Patients with OSA are prone for excessive adipose tissue deposition in the neck, which in turn, increases the upper airway narrowing. Of the imaging modalities available for assessing the upper airway, magnetic resonance imaging (MRI) is found to be useful technique for defining soft tissue abnormalities. METHODS: We prospectively studied 50 patients presenting with OSA and 50 normal controls to evaluate the role of MRI cephalometry in the diagnosis of OSA and compared the cross-sectional area and antero-posterior diameter of the upper airway in the retro-palatal airway and retro-glossal areas by MRI cephalometry. RESULTS: In comparison with controls, cases had a significantly lower cross-sectional area and antero-posterior diameter of the upper airway in the retro-palatal airway and retro-glossal areas. CONCLUSIONS: Our observations suggest that MRI cephalometry is a sensitive technique for the diagnosis of OSA.

Ligand-conjugated multiwalled carbon nanotubes for cancer targeted drug delivery.

Multiwalled carbon nanotubes (MWCNTs) are at the forefront of nanotechnology-based advancements in cancer therapy, particularly in the field of targeted drug delivery. The nanotubes are characterized by their concentric graphene layers, which give them outstanding structural strength. They can deliver substantial doses of therapeutic agents, potentially reducing treatment frequency and improving patient compliance. MWCNTs' diminutive size and modifiable surface enable them to have a high drug loading capacity and penetrate biological barriers. As a result of the extensive research on these nanomaterials, they have been studied extensively as synthetic and chemically functionalized molecules, which can be combined with various ligands (such as folic acid, antibodies, peptides, mannose, galactose, polymers) and linkers, and to deliver anticancer drugs, including but not limited to paclitaxel, docetaxel, cisplatin, doxorubicin, tamoxifen, methotrexate, quercetin and others, to cancer cells. This functionalization facilitates selective targeting of cancer cells, as these ligands bind to specific receptors overexpressed in tumor cells. By sparing non-cancerous cells and delivering the therapeutic payload precisely to cancer cells, this therapeutic payload delivery ability reduces chemotherapy systemic toxicity. There is great potential for MWCNTs to be used as targeted delivery systems for drugs. In this review, we discuss techniques for functionalizing and conjugating MWCNTs to drugs using natural and biomacromolecular linkers, which can bind to the cancer cells' receptors/biomolecules. Using MWCNTs to administer cancer drugs is a transformative approach to cancer treatment that combines nanotechnology and pharmacotherapy. It is an exciting and rich field of research to explore and optimize MWCNTs for drug delivery purposes, which could result in significant benefits for cancer patients.

In silico-guided discovery and in vitro validation of novel sugar-tethered lysinated carbon nanotubes for targeted drug delivery of doxorubicin.

CONTEXT: Multiwalled carbon nanotubes (MWCNTs) functionalized with lysine via 1,3-dipolar cycloaddition and conjugated to galactose or mannose are potential nanocarriers that can effectively bind to the lectin receptor in MDA-MB-231 or MCF-7 breast cancer cells. In this work, a method based on molecular dynamics (MD) simulation was used to predict the interaction of these functionalized MWCNTs with doxorubicin and obtain structural evidence that allows a better understanding of the drug loading and release process. The MD simulations showed that while doxorubicin only interacted with pristine MWCNTs through π-π stacking interactions, functionalized MWCNTs were also able to establish hydrogen bonds, suggesting that the functionalized groups improve doxorubicin loading. Moreover, the elevated adsorption levels observed for functionalized nanotubes further support this enhancement in loading efficiency. MD simulations also shed light on the intratumoral pH-specific release of doxorubicin from functionalized MWCNTs, which is induced by protonation of the daunosamine moiety. The simulations show that this change in protonation leads to a lower absorption of doxorubicin to the MWCNTs. The MD studies were then experimentally validated, where functionalized MWCNTs showed improved dispersion in aqueous medium compared to pristine MWCNTs and, in agreement with the computational predictions, increased drug loading capacity. Doxorubicin-loaded functionalized MWCNTs demonstrated specific release of doxorubicin in tumor microenvironment (pH = 5.0) with negligible release in the physiological pH (pH = 7.4). Furthermore, doxorubicin-free MWNCT nanoformulations exhibited insignificant cytotoxicity. The experimental studies yielded nearly identical results to the MD studies, underlining the usefulness of the method. Our functionalized MWCNTs represent promising non-toxic nanoplatforms with enhanced aqueous dispersibility and the potential for conjugation with ligands for targeted delivery of anti-cancer drugs to breast cancer cells. METHODS: The computational model of a pristine carbon nanotube was created with the buildCstruct 1.2 Python script. The lysinated functionalized groups were added with PyMOL and VMD. The carbon nanotubes and doxorubicin molecules were parameterized using the general AMBER force field, and RESP charges were determined using Gaussian 09. Molecular dynamics simulations were carried out with the AMBER 20 software package. Adsorption levels were calculated using the water-shell function of cpptraj. Cytotoxicity was evaluated via a MTT assay using MDA-MB-231 and MCF-7 breast cancer cells. Drug uptake of doxorubicin and doxorubicin-loaded MWCNTs was measured by fluorescence microscopy.

Thyroid storm presenting as congestive heart failure and protein-S deficiency-induced biventricular and internal jugular venous thrombii.

The thyroid storm is a medical emergency characterized by decompensation of one or more organ systems. Associated cardiac involvement carries poor prognosis. Early recognition and appropriate management of life-threatening thyrotoxicosis is vital to prevent the high morbidity and mortality that may accompany this disorder. We report a young lady presenting with thyroid storm presenting as acute heart failure with biventricular and bilateral internal jugular venous thrombi. In addition, she also had thyrotoxicosis-induced transient protein-S deficiency which recovered following remission.

Fatty Acid Synthase (FASN): A Patent Review Since 2016-Present.

INTRODUCTION: Fatty acid synthase (FASN), is a key metabolic enzyme involved in fatty acid biosynthesis and is an essential target for multiple disease progressions like cancer, obesity, NAFLD, etc. Aberrant expression of FASN is associated with deregulated energy metabolism of cells in these diseases. AREA COVERED: This article provides a summary of the most recent developments in the discovery of novel FASN inhibitors with potential therapeutic uses in cancer, obesity, and other metabolic disorders such as nonalcoholic fatty liver disease from 2016 to the present. The recently published patent applications and forthcoming clinical data of FASN inhibitors from both academia and the pharma industries are also highlighted in this study. EXPERT OPINION: The implication of FASN in multiple diseases has provided an impetus for developing novel inhibitors by both pharma companies and academia. Critical analysis of the patent literature reveals the exploration of diverse molecular scaffolds to identify potential FASN inhibitors that target the different catalytic domains of the enzyme. In spite of these multifaceted efforts, only one molecule, TVB-2640, has reached phase II trials for nonalcoholic steatohepatitis (NASH) and many malignancies. However, thecombined efforts of pharma companies to produce several FASN inhibitors might facilitate the clinical translation of this unique class of inhibitors. Nevertheless, concerted efforts towards developing multiple FASN inhibitors by pharma companies might facilitate the clinical translation of this novel class of inhibitors.

Virtual screening and QSAR study of some pyrrolidine derivatives as α-mannosidase inhibitors for binding feature analysis.

Virtual screening and QSAR analysis were carried out to investigate the binding features of (2R, 3R, 4S)-2-aminomethylpyrrolidine 3,4-diol and the functionalized pyrrolidine derivatives to the α-mannosidase I and II enzymes. The QSAR models (possessed considerable R(2), Q(2) values, etc.) suggested that the presence of polar property on the vdW surface (vsurf_W, vsurf_Wp, etc.) of the molecules is important along with the presence of aromatic rings (opr_violation) in the molecules (which also provide hydrophobicity to the molecules). The docking study performed on α-mannosidase I and II enzymes pointed that the main interactions occur by hydrogen bonds, hydrophobic π-π stacking contacts and salt bridges with the cation calcium (for α-mannosidase I) and close interaction with zinc ion (α-mannosidase II), respectively. The bond flexibility orientates the aromatic ring in the molecules toward the hydrophobic cavity for π-π stacking contacts with the aromatic amino acids (Phe528, Phe329 and Phe659 for α-mannosidase I and Trp95, Tyr269, Phe312, Tyr102 for α-mannosidase II). The pharmacophore analysis also supports the results derived from the docking and QSAR studies. Our results suggest that the best compound to inhibit both classes of α-mannosidase is the compound 30, which may be used to design similar and better inhibitors to next generation drugs.

Synthesis, in silico metabolic and toxicity prediction of some novel imidazolinones derivatives as potent anticonvulsant agents.

A series of 1,2,4-trisubstituted 5-imidazolinone derivatives were synthesized by Erlenmeyer condensation of benzoylglycine (hippuric acid) with different aldehydes in the presence of sodium acetate and acetic anhydride. The derivatives of the compounds were prepared by condensation of some known sulpha drugs with 5-oxazolone derivatives. The anticonvulsant activity of the compounds was determined by the protection of pentylenetetrazole-induced convulsions that was ranged from 10 to 60%. The compounds with p-OCH3, p-OH and o-Cl substitutions in the phenyl ring on 4(th) position of the imidazolinone ring exhibited good anticonvulsant activity. In silico metabolic and toxicity studies showed that all the compounds in the series are not likely to exhibit toxicity except the compounds IIIa, IIIb, VIa and VIb, that is predicted to show 29% mutagenicity and 53% irritation in comparison to the other compounds. The predicted lethal effect and hERG toxicity of the compounds showed that IIa, IVa, Va and Vb might be toxic at higher concentrations. The results successfully establish the synthesized imidazolinone derivatives as novel compounds with anticonvulsant properties, low predicted cardiotoxicity and lethal effects thus can be promising leads for further development as novel anticonvulsants.

Structural analysis of structurally diverse α-glucosidase inhibitors for active site feature analysis.

In the present investigation, a QSAR analysis on structurally diverse α-glucosidase inhibitors (andrographolide, chromenone, triazole derivatives) was performed and the developed models were validated by various validation methods (LMO, LOO, LSO, bootstrapping, Y-randomization and test set). The statistical parameters calculated for the models show that the developed models are statistically significant and have predicted the activities with small residual errors. The crossvalidated correlation coefficient (Q(2)) values obtained from different validation methods show >0.7 for both the models. Other correlations coefficient statistical parameters (R(2)(pred) and R(2)(m)) show that the developed models are reliable and robust. The leave-series-out (LSO) results reveal that the developed models can predict the activity of new compounds and its crossvalidated correlation coefficients' values are comparable with the Q(2) values obtained from other validation methods. The descriptors contributed in the selected models are suggested that the lower/reduced polarizability on the vdW surface area of the molecules and the presence of flexible bonds allow the substituents/side chains in the molecules with free movement and with lesser stretching energy which are favourable for the α-glucosidase inhibitory activity. These results reveal that the developed models are statistically significant and can be used with other molecular modelling works for designing novel α-glucosidase inhibitors with multiple activities (HIV, diabetics, cancer, etc).

Comparative structural analysis of α-glucosidase inhibitors on difference species: a computational study.

Structural feature analysis of chlorogenic acid derivatives made up of varying lengths of alkyl groups as α-glucosidases inhibitors were performed by QSAR techniques. The statistically significant models derived from the study were validated by leave one out, Y-randomization and test set methods. The predictive capacity of the models was assessed by its validation parameters such as crossvalidated correlation coefficients (Q(2)), predictive residual analysis and other correlation parameters. The results obtained from the study show that the models were constructed with vsurf like properties (vsurf_ID4, vsurf_ID7 and vsurf_CW8), partial charge (Q_VSA_FNEG) and conformation dependent charged (dipoleX) descriptors. The integy moments of hydrophobicity descriptors (ID4 and ID7) are contributed for the inhibitory activity of the α-glucosidases enzymes of both the species. The vsurf_ID7 descriptor has contributed significantly (negatively) for the inhibitory activity prediction of α-glucosidases enzymes of S. cerevisiae. The partial negative charge on the surface of the molecules is detrimental for the activity, which reveals that the active site of the enzymes may have negatively charged groups. The pharmacophore analysis results also confirm the presence of hydrophilic properties on the vdW surface of the molecules. These results explain that the active sites of α-glucosidase enzymes of both the species have the same environment for the interaction. The alkyl side chain on the molecules is important for the pharmacokinetic behavior of the molecules and reduces the interaction energy of the molecules with the water. Hence, these results will be useful for designing novel molecules with multiple activities.

Repaglinide-laden hydrogel particles of xanthan gum derivatives for the management of diabetes.

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.