25 results on '"Toreniyazov E"'
Search Results
2. Isolation, Purification of Phenolic Glycoside 1 from Moringa oleifera Seeds and Formulation of Its Liposome Delivery System.
- Author
-
Shi F, Gong M, Adu-Frimpong M, Jiang X, Wang X, Hua Q, Li T, Li J, Yu J, Toreniyazov E, Cao X, Wang Q, and Xu X
- Subjects
- Humans, Animals, Hep G2 Cells, Particle Size, Drug Delivery Systems methods, Mice, Male, Rats, Administration, Oral, Chemistry, Pharmaceutical methods, Rats, Sprague-Dawley, Liposomes, Moringa oleifera chemistry, Seeds chemistry, Glycosides chemistry, Glycosides administration & dosage, Glycosides pharmacology, Glycosides isolation & purification, Biological Availability, Phenols administration & dosage, Phenols chemistry, Phenols isolation & purification, Phenols pharmacokinetics
- Abstract
In this study, N, N '-bis {4- [(α-L- rhamnosyloxy) benzyl]} thiourea (PG-1), a phenolic glycoside compound was purified from Moringa seed. The PG-1 has attracted extensive attention due to its anti-cancer, antioxidant, anti-inflammatory and hypoglycemic properties. However, some of its physicochemical properties such as oral bioavailability has not been studied. Herein, a highly purified PG-1 was extracted and incorporated in multiple layered liposomes (PG-1-L) to avoid its burst release and enhance oral bioavailability. After appropriate characterization, it was discovered that the obtained PG-1-L was stable, homogeneous and well dispersed with the average particle size being 89.26 ± 0.23 nm. Importantly, the in vitro release and in vivo oral bioavailability of PG-1-L were significantly improved compared with PG-1. In addition, MTT results showed that compared with the free PG-1, PG-1-L displayed obvious inhibitory effect on the HepG2 cells, while the inhibitory effect on healthy non-malignant 3T6 and LO-2 cells was not significant, indicating that PG-1-L had high safety. In conclusion, PG-1-L can be used as a promising delivery system and an ideal novel approach to improve the oral bioavailability and anticancer activity of PG-1., (© 2024. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
- Published
- 2024
- Full Text
- View/download PDF
3. Preparation, characterisation, and pharmacodynamic study of myricetin pH-sensitive liposomes.
- Author
-
Li C, Du M, Meng L, Adu-Frimpong M, Gong C, Zheng S, Shi W, Wang Q, Toreniyazov E, Ji H, Cao X, Yu J, and Xu X
- Subjects
- Hydrogen-Ion Concentration, Animals, Male, Uric Acid, Biological Availability, Particle Size, Rats, Sprague-Dawley, Drug Liberation, Rats, Liposomes chemistry, Flavonoids pharmacokinetics, Flavonoids chemistry, Flavonoids administration & dosage, Flavonoids pharmacology
- Abstract
Aims: Myricetin (MYR) was incorporated into pH-sensitive liposomes in order to improve its bioavailability and anti-hyperuricemic activity., Methods: The MYR pH-sensitive liposomes (MYR liposomes) were prepared using thin film dispersion method, and assessed by particle size (PS), polydispersed index (PDI), zeta potential (ZP), encapsulation efficiency, drug loading, and in vitro release rate. Pharmacokinetics and anti-hyperuricemic activities were also evaluated., Results: The PS, PDI, ZP, encapsulation efficiency, and drug loading of MYR liposomes were 184.34 ± 1.05 nm, 0.215 ± 0.005, -38.46 ± 0.30 mV, 83.42 ± 1.07%w/w, and 6.20 ± 0.31%w/w, respectively. The release rate of MYR liposomes was higher than free MYR, wherein the cumulative value responded to pH. Besides, the Cmax of MYR liposomes was 4.92 ± 0.20 μg/mL. The level of uric acid in the M-L-H group (200 mg/kg) was reduced by 54.74%w/v in comparison with the model group., Conclusion: MYR liposomes exhibited pH sensitivity and could potentially enhance the oral bioavailability and anti-hyperuricemic efficacy of MYR.
- Published
- 2024
- Full Text
- View/download PDF
4. Preparation, characterization, pharmacokinetics and ulcerative colitis treatment of hyperoside-loaded mixed micelles.
- Author
-
Jin X, Xia X, Li J, Adu-Frimpong M, Wang X, Wang Q, Wu H, Yu Q, Ji H, Toreniyazov E, Cao X, Yu J, and Xu X
- Subjects
- Humans, Administration, Oral, Particle Size, Drug Carriers chemistry, Micelles, Colitis, Ulcerative drug therapy, Quercetin analogs & derivatives
- Abstract
At present, ulcerative colitis (UC) has become a global disease due to its high incidence. Hyperoside (HYP) is a naturally occurring flavonoid compound with many pharmacological effects. This study aimed to develop HYP-loaded mixed micelles (HYP-M) to improve oral bioavailability of HYP and to evaluate its therapeutic effect on UC. The prepared HYP-M exhibited stable physical and chemical properties, smaller particle size (PS) (21.48 ± 1.37 nm), good polydispersity index (PDI = 0.178 ± 0.013), negative Zeta potential (ZP) (- 20.00 ± 0.48 mV) and high entrapment rate (EE) (89.59 ± 2.03%). In vitro release and in vivo pharmacokinetic results showed that HYP-M significantly increased the releasing rate of HYP, wherein its oral bioavailability was 4.15 times higher than that of free HYP. In addition, HYP-M was more effective in the treatment of UC than free HYP. In conclusion, HYP-M could serve as a novel approach to improve bioavailability and increase anti-UC activity of HYP., (© 2023. Controlled Release Society.)
- Published
- 2024
- Full Text
- View/download PDF
5. Isoliquiritigenin Containing PH Sensitive Micelles for Enhanced Anti-Colitis Activity.
- Author
-
Shi F, Du M, Wang Q, Adu-Frimpong M, Li C, Zhang X, Ji H, Toreniyazov E, Cao X, Wang Q, and Xu X
- Subjects
- Rats, Animals, Drug Delivery Systems methods, Anti-Inflammatory Agents pharmacology, Hydrogen-Ion Concentration, Drug Carriers chemistry, Micelles, Colitis, Chalcones
- Abstract
Isoliquiritigenin (ISL) is known to have a variety of pharmacological activities, but its poor water solubility limits its application. In order to improve the bioavailability of ISL and its anti-colitis activity, this study aims to develop an effective drug delivery system loaded with ISL. In this study, ISL pH-sensitive micelles (ISL-M) were prepared by thin film hydration method. The micellar size (PS), polydispersity index (PDI), electrokinetic potential (ζ-potential), drug loading (DL), encapsulation rate (EE) and other physical parameters were characterized. The storage stability of ISL-M was tested, release in vitro and pharmacokinetic studies in rats were performed, and the anti-inflammatory effect of ISL-M on ulcerative colitis induced by dextran sulfate sodium (DSS) was evaluated. The results showed that PS, PDI, ZP, EE% and DL% of ISL-M were 151.15±1.04 nm, 0.092±0.014, -31.32±0.721 mV, 93.97±1.53 % and 8.42±0.34 %, respectively. Compared with unformulated ISL (F-ISL), the cumulative release rate of ISL-M in the three different media was significantly increased and showed a certain pH sensitivity. The area under drug curve (AUC
0-t ) and peak concentration (Cmax ) of ISL-M group were 2.94 and 4.06 times higher than those of ISL group. In addition, ISL-M is expected to develop new methods for increasing the bioavailability and anti-inflammatory activity of ISL., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
6. In-vitro and in-vivo evaluation and anti-colitis activity of esculetin-loaded nanostructured lipid carrier decorated with DSPE-MPEG2000.
- Author
-
Shi F, Yin W, Adu-Frimpong M, Li X, Xia X, Sun W, Ji H, Toreniyazov E, Qilong W, Cao X, Yu J, and Xu X
- Subjects
- Animals, Mice, Interleukin-6, Tumor Necrosis Factor-alpha, Inflammation, Excipients, Lipids, Colitis, Ulcerative chemically induced, Colitis, Ulcerative drug therapy
- Abstract
Objective: Encapsulation of esculetin into DSPE-MPEG2000 carrier was performed to improve its water solubility and oral bioavailability, as well as enhance its anti-inflammatory effect on a mouse model of ulcerative colitis that was induced with dextran sulphate sodium (DSS)., Methods: We determined the in-vitro and in-vivo high-performance liquid chromatographic (HPLC) analysis method of esculetin; Esculetin-loaded nanostructure lipid carrier (Esc-NLC) was prepared using a thin-film dispersion method, wherein a particle size analyser was used to measure the particle size (PS) and zeta potential (ZP) of the Esc-NLC, while a transmission electron microscope (TEM) was employed to observe its morphology. Also, HPLC was used to measure its drug loading (DL), encapsulation efficiency (EE) and the in-vitro release of the preparation, as well as investigate the pharmacokinetic parameters. In addition, its anti-colitis effect was evaluated via histopathological examination of HE-stained sections and detection of the concentrations of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1 beta (β), and IL-6 in serum with ELISA kits., Results: The PS of Esc-NLC was 102.29 ± 0.63 nm with relative standard deviation (RSD) of 1.08% (with poly-dispersity index-PDI of 0.197 ± 0.023), while the ZP was -15.67 ± 1.39 mV with RSD of 1.24%. Solubility of esculetin was improved coupled with prolonged release time. Its pharmacokinetic parameters were compared with that of free esculetin, wherein the maximum concentration of the drug in plasma was increased by 5.5 times. Of note, bioavailability of the drug was increased by 1.7 times, while the half-life was prolonged by 2.4 times. In the anti-colitis efficacy experiment, the mice in Esc and Esc-NLC groups exhibited significantly reduced levels of TNF-α, IL-1β, and IL-6 in their sera comparable to the DSS group. Colon histopathological examination revealed that mice with ulcerative colitis in both Esc and Esc-NLC groups displayed improved inflammation, amid the Esc-NLC groups having the best prophylactic treatment effect., Conclusion: Esc-NLC could ameliorate DSS-induced ulcerative colitis by improving bioavailability, prolonging drug release time and regulating cytokine release. This observation confirmed the potential of Esc-NLC to reduce inflammation in ulcerative colitis, albeit the need for follow-up research to verify the application of this strategy to clinical treatment of ulcerative colitis.
- Published
- 2023
- Full Text
- View/download PDF
7. Vitexin loaded mixed polymeric micelles: preparation, optimization, evaluation and anti-osteoporotic effect.
- Author
-
Zhang J, Li X, Xia X, Adu-Frimpong M, Shen X, He Q, Rong W, Shi F, Cao X, Ji H, Toreniyazov E, Wang Q, Yu J, and Xu X
- Subjects
- Rats, Animals, Prednisone, Polymers, Particle Size, Drug Carriers chemistry, Micelles, Zebrafish
- Abstract
In this regard, we developed vitexin (Vi)-loaded D- ɑ -tocopherol polyethylene glycol succinate, polyvinylpyrrolidone K30 and sodium cholate mixed micelles (Vi-MMs) mainly for improving oral bioavailability and enhancing anti-osteoporotic effect of Vi. Thin layer dispersion method was employed to prepare Vi-MMs, and then the optimal prescription was optimized by the orthogonal design-response surface method, wherein encapsulation efficiency (EE) was used as optimizing index. The physical properties of Vi-MMs such as appearance morphology, particle size, and zeta potential were also characterized. We further analyzed the in-vitro release of Vi and Vi-MMs in three media and investigated the pharmacokinetics of Vi and Vi-MMs in rats. Anti-osteoporotic activity of Vi and Vi-MMs was assessed by establishing a zebrafish osteoporosis model with prednisone. Drug loading, EE, particle size and zeta potential of the optimized Vi-MMs were 8.58 ± 0.13%, 93.86 ± 1.79%, 20.41 ± 0.64 nm and -10 ± 0.56 mV, respectively. The optimized Vi-MMs were shaped spherically as exhibited by transmission electron microscopic technique, with evident core shell nano-structure, well dispersed. In all three media, the release rate of Vi-MMs was significantly higher than that of free Vi. The oral bioavailability of Vi-MMs was increased by 5.6-fold compared to free Vi. In addition, alleviation of prednisone induced osteoporosis in zebrafish by Vi-MMs further demonstrated good anti-osteoporotic effect. In summary, Vi-MMs exhibited enhanced bioavailability and anti-osteoporotic effect, which is expected to be potential nanocarrier for Vi applications in drug development., (© 2023 IOP Publishing Ltd.)
- Published
- 2023
- Full Text
- View/download PDF
8. Preparation, Physical Characterization, Pharmacokinetics and Anti-Hyperglycemic Activity of Esculetin-Loaded Mixed Micelles.
- Author
-
Li X, Xia X, Zhang J, Adu-Frimpong M, Shen X, Yin W, He Q, Rong W, Shi F, Cao X, Ji H, Toreniyazov E, Wang Q, Yu J, and Xu X
- Subjects
- Rats, Animals, Mice, Administration, Oral, Solubility, Biological Availability, Particle Size, Hypoglycemic Agents pharmacology, Hypoglycemic Agents therapeutic use, Drug Carriers, Micelles, Umbelliferones
- Abstract
Despite its low water solubility, esculetin (EC) have been described to demonstrate various health benefits. Thus, we sought to develop esculetin-loaded mixed micelles (EC-M) delivery system to purposively improve biological availability and anti-hyperglycemia activity of EC. Thin-film hydration method was employed to fabricate EC-M, amid characterization with transmission electron microscopic analysis (TEM), coupled with physical properties such as particle size (PS), poly-dispersity index (PDI), zeta-potential (ZP) and stability testing. We analyzed in-vitro release and studied EC-M pharmacokinetics in rats. The hyperglycemic mice model was established with streptozotocin (STZ) to evaluate anti-hyperglycemic activity of EC-M. The PS, PDI and ZP of EC-M were 47.97 ± 0.41 nm, 0.189 ± 0.005 and -25.55 ± 0.28 mV, respectively. The release rate of EC-M increased comparable to free EC in the three media. The oral biological availability and half-life of EC-M increased respectively by 3.06 and 1.45 folds compared to free EC. Besides, we observed 46.21% decrease in blood glucose of mice in EC-M group comparable to the model control, wherein, the anti-hyperglycemic effect of EC-M was better compared to free EC. Conclusively, EC-M may ideally serve as a novel approach to enhance biological availability and increased anti-hyperglycemic activity of EC., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
9. Preparation, in vitro and in vivo evaluation of pinocembrin-loaded TPGS modified liposomes with enhanced bioavailability and antihyperglycemic activity.
- Author
-
Shen X, Rong W, Adu-Frimpong M, He Q, Li X, Shi F, Ji H, Toreniyazov E, Xia X, Zhang J, Wang Q, Yu J, and Xu X
- Subjects
- Mice, Animals, Biological Availability, Hypoglycemic Agents pharmacology, Polyethylene Glycols chemistry, Particle Size, Liposomes chemistry, Diabetes Mellitus, Experimental drug therapy
- Abstract
Purpose: To prepare polyethylene glycol succinate-vitamin E modified pinocembrin (PCB)-loaded liposomes (PCBT-liposomes) and evaluate PCBT-liposomal pharmacokinetics and antihyperglycemic activity., Significance: The novel PCBT-liposomes demonstrated a promising application prospect as a nano drug carrier for future research., Methods: Thin film dispersion was used to prepare PCBT-liposomes. We measured a series of characterization, followed by in vitro cumulative release, in vivo pharmacokinetic study, and antihyperglycemic activity evaluation., Results: PCBT-liposomes displayed spherical and bilayered nanoparticles with mean particle size (roughly 92 nm), negative zeta potential (about -26.650 mV), high drug encapsulation efficiency (87.32 ± 1.34%) and good storage (at 4 or 25 °C) stability during 48 h after hydration. The cumulative release rate of PCBT-liposomes was markedly higher than free PCB in four different pH media. In vivo investigation showed that PCBT-liposomes could obviously improve oral bioavailability of PCB by 1.96 times, whereas the C
max , MRT0- t , and T1/2 of PCBT-liposomes were roughly 1.700 ± 0.139 µg·mL-1 , 12.695 ± 1.647 h, and 14.244 h, respectively. In terms of biochemical analysis, aspartate amino-transferase (AST), alanine amino-transferase (ALT), interleukin-1 (IL-1), and tumor necrosis factor-α (TNF-α) concentrations in serum of diabetic mice were respectively decreased 28.28%, 17.23%, 17.77%, and 8.08% after PCBT-liposomal treatment., Conclusion: These results show PCBT-liposomal preparation as an excellent nano-carrier which has the potential to improve water solubility, bioavailability, and antihyperglycemic activity of PCB, amid broadening the application of PCB in the clinical settings.- Published
- 2022
- Full Text
- View/download PDF
10. Preparation of Pinocembrin-Loaded F127/MPEG-PDLLA Polymer Micelles and Anti-Osteoporotic Activity.
- Author
-
Cao X, He Q, Adu-Frimpong M, Shen X, Rong W, Li X, Zhang J, Xia X, Shi F, Ji H, Toreniyazov E, Wang Q, Yu J, and Xu X
- Subjects
- Animals, Drug Carriers, Drug Delivery Systems methods, Particle Size, Polyethylene Glycols, Polyethylenes, Polymers, Polypropylenes, Prednisolone, Solubility, Water, Zebrafish, Flavanones pharmacology, Micelles
- Abstract
Pinocembrin (PCB) is 5,7-dihydroxyl flavanone and has multiple pharmacological activities, namely, anti-inflammation, anti-osteoporotic, and so on. However, low water solubility and bioavailability have hindered its application. Herein, we aimed to increase its bioavailability through preparation of F127/MPEG-PDLLA polymer micelles (PCB-M). We characterized the micelles through appropriate attributes such as analysis of particle size (PS), polydispersity (PDI), transmission electron microscopic (TEM) image, stability test, and evaluation of in vitro release of drug. After physical characterization, the respective PS, PDI, and entrapment efficiency (EE) of PCB-M were estimated to be 27.63 ± 0.17 nm, 0.055 ± 0.02, and 90.53 ± 0.01%. Fluorescence probe method was employed to measure critical micelle concentration (CMC) of PCB-M, we observed CMC was low, thereby suggesting that PCB-M had good stability. In vitro release analysis indicated that the rate of cumulative PCB release from PCB-M was greater than 90% in each medium compared with free PCB, which was less than 40%, thus pointing to a significantly improved solubility of PCB. In vivo pharmacokinetic results showed that oral biological availability of PCB-M increased 5.3 folds comparable to free PCB. The effects of PCB on osteoblasts and ALP activities were investigated; subsequently, zebrafish osteoporotic model was established with prednisolone to study the anti-osteoporotic effects of PCB and PCB-M. The results showed that PCB improved osteoporosis with PCB-M being more effective than free PCB. Finally, PCB-M can be used as a promising method to improve the solubility of PCB, while the bioavailability and anti-osteoporotic effect of PCB could be improved, thus laying a foundation for clinical use in the future., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)
- Published
- 2022
- Full Text
- View/download PDF
11. Hyperoside-loaded TPGs/mPEG-PDLLA self-assembled polymeric micelles: preparation, characterization and in vitro / in vivo evaluation.
- Author
-
Xia X, Zhang J, Adu-Frimpong M, Li X, Shen X, He Q, Rong W, Ji H, Toreniyazov E, Xu X, Yu J, and Wang Q
- Subjects
- Drug Carriers chemistry, Particle Size, Polymers chemistry, Quercetin analogs & derivatives, Solubility, Micelles, Polyethylene Glycols chemistry
- Abstract
Hyperoside (Hyp) self-assembled polymeric micelles (Hyp-PMs) were purposely developed to enhance aqueous solubility, in vivo availability and anti-oxidative effect of Hyp. In preparing Hyp-PMs, we employed the thin film dispersion method with the micelles consisting of TPGs and mPEG2000-PDLLA3000. The particle size, polydispersity index and zeta potential of Hyp-PMs were 67.42 ± 1.44 nm, 0.229 ± 0.015 and -18.67 ± 0.576 mV, respectively, coupled with high encapsulation efficiency (EE)of 90.63 ± 1.45% and drug loading (DL) of 6.97 ± 1.56%. Furthermore, the value of critical micelle concentration (CMC) was quite low, which indicated good stability and improved self-assembly ability of Hyp-PMs. Also, trend of in vitro Hyp release from Hyp-PMs demonstrated enhanced solubility of Hyp. Similarly, in comparison with free Hyp, oral bioavailability of Hyp-PMs was improved (about 8 folds) whilst half-life of Hyp-PMs was extended (about 3 folds). In vitro anti-oxidative effect showed obvious strong scavenging DPPH capability of Hyp-PMs, which may be attributed to its smaller size and better solubility. Altogether, Hyp-PMs may serve as a possible strategy to potentially enhance aqueous solubility, bioavailability and anti-oxidative effect of Hyp, which may play a key role in Hyp application in the pharmaceutical industries.
- Published
- 2022
- Full Text
- View/download PDF
12. Pinocembrin polymeric micellar drug delivery system: preparation, characterisation and anti-hyperuricemic activity evaluation.
- Author
-
Rong W, Shen X, Adu-Frimpong M, He Q, Zhang J, Li X, Xia X, Shi F, Cao X, Ji H, Toreniyazov E, Wang Q, Yu J, and Xu X
- Subjects
- Administration, Oral, Animals, Biological Availability, Drug Carriers chemistry, Flavanones, Particle Size, Polymers chemistry, Rats, Rats, Sprague-Dawley, Solubility, Drug Delivery Systems methods, Micelles
- Abstract
Aim: Hydrophobic pinocembrin (PCB) was incorporated into a new nano-drug delivery system to enhance solubility, bioavailability and anti-hyperuricemic activity of the drug. Methods: We fabricated PCB loaded polymeric micelles (PCB-FPM) by thin film dispersion method and appropriately determined their physical characteristics. The oral relative bioavailability and anti-hyperuricemic activity of PCB-FPM and free PCB were observed. Results: The optimum particle size of the micelles was 19.90 ± 0.93 nm. PCB-FPM exhibited great stability within 18 days, coupled with lower cytotoxicity and higher biocompatibility. Moreover, the percent cumulative release of PCB-FPM was much higher than free PCB in the dissolution media. The oral bioavailability of PCB-FPM was increased by 2.61 times compared with free PCB. Uric acid (UA) level of rats was reduced in PCB-FPM group (200 mg/kg) by 78.82% comparable to the model control. Conclusion: PCB-FPM may become an ideal strategy to increase oral in-vivo availability and anti-hyperuricemic activity of PCB.
- Published
- 2022
- Full Text
- View/download PDF
13. Liquiritin-Hydroxypropyl-Beta-Cyclodextrin Inclusion Complex: Preparation, Characterization, Bioavailability and Antitumor Activity Evaluation.
- Author
-
Wang Q, Zhang K, Weng W, Chen L, Wei C, Bao R, Adu-Frimpong M, Cao X, Yu Q, Shi F, Toreniyazov E, Ji H, Xu X, and Yu J
- Subjects
- 2-Hydroxypropyl-beta-cyclodextrin chemistry, Biological Availability, Calorimetry, Differential Scanning, Flavanones, Glucosides, Solubility, Spectroscopy, Fourier Transform Infrared, Water, X-Ray Diffraction, beta-Cyclodextrins chemistry
- Abstract
The pharmacological activities of liquiritin (LT) are greatly limited by its insolubility and low oral absorption. The purpose of this study was to prepare LT-hydroxypropyl-beta-cyclodextrin inclusion complex (LT-HP-β-CD) to increase water solubility, oral bioavailability and antitumor effect of LT. Herein, saturated aqueous solution method was applied to prepare the LT-HP-β-CD prior to characterization via scanning electron microscope (SEM), infrared radiation (IR) spectroscopy, X-ray diffraction analysis (XRD), and differential scanning calorimetry (DSC). Also, in vitro release and in vivo pharmacokinetics were evaluated. Moreover, the anti-tumor activity of the formulation was investigated in the A549 lung cancer cells. The results of SEM, IR, XRD and DSC showed that LT-HP-β-CD was successfully formulated. In vitro release and oral bioavailability of LT-HP-β-CD compared with the free LT was significantly higher. Successfully, antitumor effect of LT was remarkably enhanced by the preparation of LT-HP-β-CD. Altogether, the LT-HP-β-CD represents a potential carrier for enhancing the water solubility and oral bioavailability of LT coupled with antitumor activity enhancement., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
- Full Text
- View/download PDF
14. Enhanced oral bioavailability and anti-hyperuricemic activity of liquiritin via a self-nanoemulsifying drug delivery system.
- Author
-
Wei C, Wang Q, Weng W, Adu-Frimpong M, Toreniyazov E, Ji H, Xu X, and Yu J
- Subjects
- Administration, Oral, Biological Availability, Emulsions, Flavanones, Glucosides, Particle Size, Solubility, Surface-Active Agents, Drug Delivery Systems, Nanoparticles
- Abstract
Background: This study focused on the development of a self-nanoemulsifying drug delivery system (SNEDDS) to improve, potentially, the solubility and oral bioavailability of liquiritin (LQ)., Methods: The solubility of LQ in different types of excipient, namely oils (OLs), emulsifiers (EMs), and co-emulsifiers (CO-EMs), was evaluated, and a pseudo-ternary phase diagram (PTPD) and the formulation optimization were established. The prepared self-nanoemulsifying drug delivery system of liquiritin (LQ-SNEDDS) was assessed using droplet size (DS), zeta potential (ZP), polydispersity index (PDI), droplet morphology, drug release in vitro, and oral bioavailability., Results: After the dilution of the LQ-SNEDDS, a transparent nanoemulsion was obtained with an acceptable DS (24.70 ± 0.73 nm), ZP (-18.69 ± 1.44 mV), and PDI (0.122 ± 0.006). The LQ-SNEDDS that was developed had a better release rate in vitro than the free LQ suspension. Pharmacokinetic evaluation showed that the relative oral bioavailability of LQ-SNEDDS was increased by 5.53 times, and LQ-SNEDDS exhibited a delayed half life and longer retention time in comparison with those of free LQ. Similarly, LQ-SNEDDS had a better urate lowering effect and provided better organ protection than free LQ at the same dose (P < 0.05)., Conclusions: The incorporation of LQ into SNEDDS could serve as a promising approach to improve the solubility, oral bioavailability, and anti-hyperuricemic effect of LQ. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)
- Published
- 2022
- Full Text
- View/download PDF
15. Enhancement of oral bioavailability and anti-hyperuricemic activity of aloe emodin via novel Soluplus®-glycyrrhizic acid mixed micelle system.
- Author
-
Shi F, Chen L, Wang Y, Liu J, Adu-Frimpong M, Ji H, Toreniyazov E, Wang Q, Yu J, and Xu X
- Subjects
- Administration, Oral, Animals, Anthraquinones, Biological Availability, Phosphates, Polyethylene Glycols chemistry, Polyvinyls, Rats, Glycyrrhizic Acid, Micelles
- Abstract
The objective of this study was to fabricate a novel drug delivery system using Soluplus® (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer) and glycyrrhizic acid to improve solubility, bioavailability, and anti-hyperuricemic activity of aloe emodin (AE). The AE-loaded mixed micelles (AE-M) were prepared by thin-film hydration method. The optimal AE-M contained small-sized (30.13 ± 1.34 nm) particles with high encapsulation efficiency (m/m, %) of 90.3 ± 1.08%. The release rate of AE increased in the micellar formulation than that of free AE in the four media (DDW, pH 7.0; phosphate buffer solution, pH 7.4; phosphate buffer solution, pH 6.8; and hydrochloric acid aqueous solution, pH 1.2). In comparison to free AE, the pharmacokinetic study of AE-M showed that its relative oral bioavailability increased by 3.09 times, indicating that mixed micelles may promote gastrointestinal absorption. More importantly, AE-M effectively reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in model rats. The degree of ankle swelling, serum levels of interleukin (IL)-1, and IL-6-related inflammatory factors levels all decreased in the gouty arthritis model established via monosodium urate (MSU) crystals. Taken together, the AE-M demonstrated the potential to improve the bioavailability, anti-hyperuricemic activity, and anti-inflammation of AE., (© 2021. Controlled Release Society.)
- Published
- 2022
- Full Text
- View/download PDF
16. Preparation, characterization, pharmacokinetics, and antirenal injury activity studies of Licochalcone A-loaded liposomes.
- Author
-
Liu J, Zhu Z, Yang Y, Adu-Frimpong M, Chen L, Ji H, Toreniyazov E, Wang Q, Yu J, and Xu X
- Subjects
- Animals, Biological Availability, Mice, Solubility, Chalcones pharmacology, Liposomes chemistry
- Abstract
A liposome of Licochalcone A (LCA-Liposomes) was purposively prepared to ameliorate the low in vivo availability and efficacy of LCA. Physical characterization of LCA-Liposomes was carried out mainly by determining particle size, morphology, zeta potential (Z-potential), and efficiency of LCA encapsulation (EE) via appropriate techniques. Also, the rate of LCA release in vitro and distribution in vivo (plasma and tissues) was evaluated. Evaluation of the antirenal activity of LCA-liposomes was carried out by establishing chronic renal failure (CRF) model in mice through intragastric administration of adenine (200 mg/kg) and subsequent determination of biochemical parameters and examination of tissue sections. Respectively, the mean size of liposomal particles, Z-potential and EE of LCA-Liposomes were 71.78 ± 0.99 nm, -38.49 ± 0.06 mV, and 97.67 ± 1.72%. Pharmacokinetic and tissue distribution studies showed that LCA-Liposomes could improve the availability of LCA in the blood and tissues, whereas during pharmacodynamics studies, the liposome effectively improved the therapeutic effect of LCA on CRF mice by potentially protecting the renal tissues while exhibiting antioxidant activity. In conclusion, LCA-Liposomes could effectively improve the bioavailability of LCA and provide platform for the development of LCA-related functional products. PRACTICAL APPLICATIONS: As a traditional Chinese medicine, licorice is widely used in food and pharmaceutical industries. LCA is a small molecule flavonoid extracted from the root of licorice. In this study, LCA was loaded on liposome carriers, which significantly improved the water solubility and oral bioavailability, and proved that LCA-Liposomes have certain therapeutic effects on chronic renal failure, thereby providing a basis for the development of LCA into drugs or functional food in the future., (© 2021 Wiley Periodicals LLC.)
- Published
- 2022
- Full Text
- View/download PDF
17. SMEDDS for improved oral bioavailability and anti-hyperuricemic activity of licochalcone A.
- Author
-
Zhu Z, Liu J, Yang Y, Adu-Frimpong M, Ji H, Toreniyazov E, Wang Q, Yu J, and Xu X
- Subjects
- Administration, Oral, Animals, Biological Availability, Chalcones, Drug Delivery Systems, Emulsions therapeutic use, Particle Size, Rats, Rats, Sprague-Dawley, Solubility, Hyperuricemia drug therapy
- Abstract
The aim of this study was to develop licochalcone A-loaded self-microemulsifying drug delivery system (LCA-SMEDDS) to improve bioavailability and anti-hyperuricemic activity of hydrophobic natural compound licochalcone A (LCA). The prepared LCA-SMEDDS was characterised by transmission electron microscopy analysis, particle size, polymer dispersity index (PDI), zeta potential, stability tests and in vitro release analysis. LCA-SMEDDS and free LCA were orally administered to Sprague-Dawley rats to investigate respective bioavailability. The hyperuricaemia rat model was established to evaluate anti-hyperuricemic activity. The particle size, PDI, and zeta potential of LCA-SMEDDS were 25.68 ± 0.79 nm, 0.074 ± 0.024, -14.37 ± 2.17 mV. The oral bioavailability of LCA-SMEDDS was increased 2.36-fold compared with the free LCA. The uric acid level of LCA-SMEDDS group (200 mg/kg) was decreased 60.08% compared with model control group. The developed LCA-SMEDDS could be an outstanding candidate for improving oral bioavailability and anti-hyperuricemic activity of LCA.
- Published
- 2021
- Full Text
- View/download PDF
18. Mixed micelles for enhanced oral bioavailability and hypolipidemic effect of liquiritin: preparation, in vitro and in vivo evaluation.
- Author
-
Weng W, Wang Q, Wei C, Adu-Frimpong M, Toreniyazov E, Ji H, Yu J, and Xu X
- Subjects
- Administration, Oral, Animals, Biological Availability, Drug Carriers, Flavanones chemistry, Flavanones pharmacology, Glucosides chemistry, Glucosides pharmacology, Mice, Particle Size, Solubility, Flavanones administration & dosage, Glucosides administration & dosage, Micelles
- Abstract
Objectives: Liquiritin, as one of the main flavonoids in Glycyrrhiza, exhibits extensive pharmacological effects, such as the anti-oxidant, anti-inflammatory, anti-tumor and so on. Herein, the aqueous solubility and oral bioavailability of liquiritin was purposely enhanced via the preparation of the mixed micelles., Methods: The liquiritin-loaded micelles (LLM) were fabricated via thin-film dispersion method. The optimal LLM formulation was evaluated through physical properties including particle size (PS), encapsulation efficiency (EE) and drug loading (DL). In vitro accumulate release as well as in vivo pharmacokinetics were also evaluated. Moreover, the hypolipidemic activity of LLM was observed in the hyperlipidemia mice model., Results: The LLM exhibited a homogenous spherical shape with small mean PS, good stability and high encapsulation efficiency. The accumulate release rates in vitro of the LLM were obviously higher than free liquiritin. The oral bioavailability of the formulation was heightened by 3.98 times in comparison with the free liquiritin. More importantly, LLM increased the hypolipidemic and effect of alleviating lipid metabolism disorder in hepatocytes of liquiritin in hyperlipidemia mice model., Conclusions: Collectively, the improved solubility of liquiritin in water coupled with its enhanced oral bioavailability and concomitant hypolipidemic activity could be attributed to the incorporation of the drug into the mixed micelles.
- Published
- 2021
- Full Text
- View/download PDF
19. Enhancement of oral bioavailability and hypoglycemic activity of liquiritin-loaded precursor liposome.
- Author
-
Wang Q, Wei C, Weng W, Bao R, Adu-Frimpong M, Toreniyazov E, Ji H, Xu XM, and Yu J
- Subjects
- Administration, Oral, Animals, Biological Availability, Flavanones, Glucosides, Mice, Particle Size, Solubility, Hypoglycemic Agents, Liposomes
- Abstract
The purpose of this study was to develop a precursor liposome nano-delivery system for liquiritin (LT) to improve its solubility, oral bioavailability, and efficacy. The characterizations of the particle diameter, zeta potential, polydispersity index (PDI), droplet morphology, drug release in vitro, and oral bioavailability of the prepared LT precursor liposomes (LTMs) were carried out. In addition, streptozotocin intraperitoneal injection successfully induced diabetic mouse model, while the LT hypoglycemic effect, oral glucose tolerance, biochemical parameters and pathological sections were studied. The prepared LTMs were diluted to obtain a clear and transparent solution with a diameter of 91.84 ± 1.85 nm, zeta potential of -38.59 ± 2.65 mV and PDI of 0.215 ± 0.016. The in vitro release of the LTMs was superior to that of the free LT suspension, which may be related to the increased solubility of LT, as well as the small diameter and increased surface area. The obtained pharmacokinetic parameters indicated that the relative oral bioavailability of LTMs was increased by 8.8 times compared with the free LT suspension. Pharmacodynamic studies showed that LTMs effectively improved LT's hypoglycemic effect and diabetes-related organ repair, simultaneously confirmed its antioxidant activity. These results implied that the LTMs was an effective method to improve the solubility, oral bioavailability, and hypoglycemic activity of LT., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
20. Preparation, characterization, pharmacokinetics and anti-hyperuricemia activity studies of myricitrin-loaded proliposomes.
- Author
-
Weng W, Wang Q, Wei C, Man N, Zhang K, Wei Q, Adu-Frimpong M, Toreniyazov E, Ji H, Yu J, and Xu X
- Subjects
- Administration, Oral, Animals, Biological Availability, Chemistry, Pharmaceutical, Drug Liberation, Drug Stability, Flavonoids chemistry, Flavonoids pharmacokinetics, Freeze Drying, Gout Suppressants chemistry, Gout Suppressants pharmacokinetics, Hyperuricemia blood, Hyperuricemia pathology, Kidney drug effects, Kidney pathology, Liposomes, Liver drug effects, Liver pathology, Male, Rats, Sprague-Dawley, Uric Acid blood, Flavonoids administration & dosage, Gout Suppressants administration & dosage, Hyperuricemia drug therapy
- Abstract
Myricitrin has many pharmacological effects, such as anti-inflammation, liver protection and anti-oxidation. However, its clinical application is limited by poor solubility and low oral bioavailability. The preparation of myricitrin-loaded proliposomes (MPs) was achieved via the combination of thin-film dispersion technique and freeze-drying method. The in vitro release of MPs compared with free myricitrin was measured in different dissolution media while the pharmacokinetic study was also conducted in rats. Moreover, the uric acid-lowering activity of MPs was investigated in the hyperuricemic rat model. The prepared myricitrin appeared to be spherical. Notably, compared with the free myricitrin, the cumulative release in vitro and in vivo oral bioavailability of MPs were markedly increased. Besides, the MPs could significantly lower the serum uric acid level as well as ameliorate liver and kidney damage in hyperuricemic rats compared with the model group. Therefore, the present work supports the fact that MPs improved the oral bioavailability of myricitrin for the prospect of clinical application., (Copyright © 2019 Elsevier B.V. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
21. Self-Micro-Emulsifying Controlled Release of Eugenol Pellets: Preparation, In vitro/In vivo Investigation in Beagle Dogs.
- Author
-
Wang Q, Guo M, Adu-Frimpong M, Zhang K, Yang Q, Toreniyazov E, Ji H, Xu X, Cao X, and Yu J
- Subjects
- Administration, Oral, Animals, Biological Availability, Cellulose analogs & derivatives, Cellulose chemistry, Chemistry, Pharmaceutical methods, Delayed-Action Preparations, Dogs, Emulsions chemistry, Eugenol administration & dosage, Eugenol chemistry, Hypromellose Derivatives chemistry, Particle Size, Polyethylene Glycols chemistry, Eugenol pharmacokinetics
- Abstract
This report aimed to formulate self-micro-emulsifying (SMEDDS) controlled-release pellets delivery system to improve aqueous solubility and in vivo availability of eugenol, a main constituent of clove oil with multiple pharmacological activities. The optimal formulation of eugenol-SMEDDS was eugenol: ethyl oleate: cremophor EL: 1, 2-propylene glycol at the ratio of 5:5:12:8. The SMEDDS were observed under transmission electron microscopy (TEM), and the size distribution was measured with dynamic laser light scatting (DLS). The particle size, index of dispersity (PDI), and zeta potential (Z-potential) were 68.8 ± 0.1 nm, 0.285 ± 0.031, and - 11.62 ± 0.63 mV, respectively. Eugenol-SMEDDS exhibited substantial increased in vitro dissolution compared with the free eugenol. The eugenol-SMEDDS sustained-release pellets (eugenol-SMEDDS-SR pellets) comprising of eugenol-SMEDDS, hydroxypropyl methylcellulose (HPMC), microcrystalline cellulose (MCC), and ethyl cellulose (EC) coats were obtained via extrusion spheronization technique. Consequently, the obtained pellets observed under scanning electron microscopy (SEM) showed spherical shape with smooth surface, desirable drug loading capacity (7.18 ± 0.17%), greater stability, and controlled release. Meanwhile, the oral test showed that bioavailability of eugenol in pellets was highly improved 23.6-fold to the free eugenol. Overall, these results suggested that the improvement of the oral bioavailability of eugenol-SMEDDS-SR could be due to the successful incorporation of the drug into SMEDDS.
- Published
- 2019
- Full Text
- View/download PDF
22. Anti-hyperuricemic property of 6-shogaol via self-micro emulsifying drug delivery system in model rats: formulation design, in vitro and in vivo evaluation.
- Author
-
Yang Q, Wang Q, Feng Y, Wei Q, Sun C, Firempong CK, Adu-Frimpong M, Li R, Bao R, Toreniyazov E, Ji H, Yu J, and Xu X
- Subjects
- Administration, Oral, Animals, Biological Availability, Chemistry, Pharmaceutical methods, Drug Delivery Systems methods, Male, Mice, Particle Size, Polyethylene Glycols chemistry, Rats, Rats, Sprague-Dawley, Solubility drug effects, Surface-Active Agents chemistry, Catechols administration & dosage, Catechols chemistry, Emulsions administration & dosage, Emulsions chemistry, Hyperuricemia drug therapy
- Abstract
The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger ( Zingiber officinale Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00 ± 0.26 nm and 0.18 ± 0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.
- Published
- 2019
- Full Text
- View/download PDF
23. Enhancement of Oral Bioavailability and Anti-hyperuricemic Activity of Isoliquiritigenin via Self-Microemulsifying Drug Delivery System.
- Author
-
Zhang K, Wang Q, Yang Q, Wei Q, Man N, Adu-Frimpong M, Toreniyazov E, Ji H, Yu J, and Xu X
- Subjects
- Administration, Oral, Animals, Biological Availability, Emulsions, Enzyme Inhibitors administration & dosage, Enzyme Inhibitors blood, Male, Polyethylene Glycols administration & dosage, Polyethylene Glycols metabolism, Rats, Rats, Sprague-Dawley, Solubility, Surface-Active Agents administration & dosage, Surface-Active Agents metabolism, Chalcones administration & dosage, Chalcones blood, Drug Delivery Systems methods, Hyperuricemia blood, Hyperuricemia drug therapy
- Abstract
The aim of this study was to develop a self-microemulsifying drug delivery system (SMEDDS) for enhancement of the oral bioavailability of isoliquiritigenin (ISL) as well as evaluate its in vivo anti-hyperuricemic effect in rats. The ISL-loaded self-microemulsifying drug delivery system (ISL-SMEDDS) was comprised of ethyl oleate (EO, oil phase), Tween 80 (surfactant), and PEG 400 (co-surfactant). The ISL-SMEDDS exhibited an acceptable narrow size distribution (44.78 ± 0.35 nm), negative zeta potential (- 10.67 ± 0.86 mV), and high encapsulation efficiency (98.17 ± 0.24%). The in vitro release study indicated that the release rates of the formulation were obviously higher in different release media (HCl, pH 1.2; PBS, pH 6.8; double-distilled water, pH 7.0) compared with the ISL solution. The oral bioavailability of the ISL-SMEDDS was enhanced by 4.71 times in comparison with the free ISL solution. More importantly, ISL-SMEDDS significantly reduced uric acid level by inhibiting xanthine oxidase (XOD) activity in the model rats. Collectively, the prepared ISL-SMEDDS proved to be potential carriers for enhancing the solubility and oral bioavailability of ISL, as well as ameliorating its anti-hyperuricemic effect.
- Published
- 2019
- Full Text
- View/download PDF
24. Preparation, in vitro and in vivo evaluation of isoliquiritigenin-loaded TPGS modified proliposomes.
- Author
-
Liu J, Wang Q, Adu-Frimpong M, Wei Q, Xie Y, Zhang K, Wei C, Weng W, Ji H, Toreniyazov E, Xu X, and Yu J
- Subjects
- Administration, Oral, Animals, Drug Compounding, Drug Liberation, Drug Stability, Liposomes, Liver metabolism, Mice, Inbred ICR, Particle Size, Rats, Sprague-Dawley, Solubility, Tissue Distribution, Chalcones administration & dosage, Chalcones chemistry, Chalcones pharmacokinetics, Vitamin E administration & dosage, Vitamin E chemistry, Vitamin E pharmacokinetics
- Abstract
Isoliquiritigenin (ISL) has a great variety of pharmacological effects especially liver cancer therapy, but its poor solubility, bioavailability and liver targeting have limited its clinical use. In order to solve the aforementioned shortcomings, the TPGS-modified proliposomes loaded with ISL (ISL-TPGS-PLP) was prepared in this study. ISL-TPGS-PLP was fabricated via thin-film dispersion method and was characterized by the appearance, particle size, zeta potential and morphology. HPLC was used to evaluate entrapment efficiency (EE), in vitro release and stability of ISL-TPGS-PLP single or combined while appropriate physicochemical parameters were measured with DLS. Meanwhile, the pharmacokinetics and tissue distribution were also studied after oral administration. The results demonstrated that ISL-TPGS-PLP had a mean size of 23.8 ± 0.9 nm, high EE of 97.33 ± 0.40%. More importantly, nearly 90% ISL was released from ISL-TPGS-PLP within 24 h while only 50% was released from ISL suspension. In the pharmacokinetics study, the area under the curve (AUC
0-24h) of ISL-TPGS-PLP was 1.53 times higher than that of ISL suspension. The Tissue distribution study showed that the ISL released from ISL-TPGS-PLP was higher in the liver than the free ISL suspension. Altogether, ISL-TPGS-PLP could ameliorate the ISL solubility, bioavailability and liver targeting ability, suggesting that ISL-TPGS-PLP could serve as a promising nanocarrier for liver cancer therapy., (Copyright © 2019 Elsevier B.V. All rights reserved.)- Published
- 2019
- Full Text
- View/download PDF
25. The characterisation, pharmacokinetic and tissue distribution studies of TPGS modified myricetrin mixed micelles in rats.
- Author
-
Wei C, Wang Q, Weng W, Wei Q, Xie Y, Adu-Frimpong M, Toreniyazov E, Ji H, Xu X, and Yu J
- Subjects
- Animals, Antioxidants pharmacokinetics, Biological Availability, Flavonoids pharmacokinetics, Male, Rats, Sprague-Dawley, Tissue Distribution, Antioxidants administration & dosage, Drug Carriers chemistry, Flavonoids administration & dosage, Micelles, Vitamin E chemistry
- Abstract
This study was designed to investigate the bioavailability and targeting of myricetrin-loaded ternary micelles modified with and without TPGS. The particle diameters of myricetrin-loaded micelles and myricetrin-loaded-TPGS micelle were 30.93 ± 1.34 nm and 26.42 ± 0.89 nm, respectively, while their respective encapsulation efficiencies (m/m, %) were 83.3 ± 1.08 and 93.8 ± 1.18. The release rate of myricetrin in the micellar system clearly exceeded the free myricetrin in the three media (pH 6.8 phosphate buffer, pH 1.2 HCl solution and double distilled water). In vivo studies displayed that the bioavailability of myricetrin mixed micelles was remarkably improved than the free drug after oral administration. Moreover, the results of tissue distribution showed that myricetrin-loaded-TPGS micelles accumulated well in the liver tissue. Based on these results, it was speculated that myricetrin-loaded-TPGS micelles might act as a promising carrier for liver targeting with improved hepatic concentration of myricetrin compared with the myricetrin-loaded micelles.
- Published
- 2019
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.