Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus
In the past, curcumin was the go-to medication for diabetes, but recent studies have shown that tetrahydrocurcumin is more effective. The problem is that it's not very soluble in water or very bioavailable. So, our research aims to increase the bioavailability and anti-diabetic efficacy of tetr...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
|
| Series: | Saudi Pharmaceutical Journal |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016423002220 |
| _version_ | 1797689487673786368 |
|---|---|
| author | Jai Bharti Sharma Shailendra Bhatt Abhishek Tiwari Varsha Tiwari Manish Kumar Ravinder Verma Deepak Kaushik Tarun Virmani Girish Kumar Omkulthom Al kamaly Asmaa Saleh Mohammed Khalid Parvez Abdulsalam Alhalmi |
| author_facet | Jai Bharti Sharma Shailendra Bhatt Abhishek Tiwari Varsha Tiwari Manish Kumar Ravinder Verma Deepak Kaushik Tarun Virmani Girish Kumar Omkulthom Al kamaly Asmaa Saleh Mohammed Khalid Parvez Abdulsalam Alhalmi |
| author_sort | Jai Bharti Sharma |
| collection | DOAJ |
| description | In the past, curcumin was the go-to medication for diabetes, but recent studies have shown that tetrahydrocurcumin is more effective. The problem is that it's not very soluble in water or very bioavailable. So, our research aims to increase the bioavailability and anti-diabetic efficacy of tetrahydrocurcumin in streptozotocin-induced diabetic rats by synthesizing tetrahydrocurcumin-loaded solid lipid nanoparticles. Box Behnken Design was employed for the optimization of tetrahydrocurcumin-loaded solid lipid nanoparticles (THC-SLNs). The optimal formulation was determined by doing an ANOVA to examine the relationship between the independent variables (drug-to-lipid ratio, surfactant concentration, and co-surfactant concentration) and the dependent variables (particle size, percent entrapment efficiency, and PDI). Particle size, PDI, and entrapment efficiency all showed statistical significance based on F-values and p-values. The optimized batch was prepared using a drug-to-lipid ratio (1:4.16), 1.21% concentration of surfactant, and 0.4775% co-surfactant (observed with a particle size of 147.1 nm, 83.58 ± 0.838 % entrapment efficiency, and 0.265 PDI, and the values were found very close with the predicted ones. As the THC peak vanishes from the DSC thermogram of the improved formulation, this indicates that the drug has been transformed from its crystalline form into its amorphous state. TEM analysis of optimized formulation demonstrated mono-dispersed particles with an average particle size of 145 nm which are closely related to zetasizer’s results. In-vitro release study of optimized formulation demonstrated burst release followed by sustained release up to 71.04% throughout 24 hrs. Increased bioavailability of the adjusted THC-SLN was found in an in vivo pharmacokinetics research with 9.47 folds higher AUC(0-t) compared to plain THC-suspension. Additionally, pharmacodynamic experiments of optimized formulation demonstrated a marked decrease in blood glucose level to 63.7% and increased body weight from 195.8 ± 7.223 to 231.2 ± 7.653 on the 28th day of the study and showed a better anti-diabetic effect than plain drug suspension. Results of stability studies revealed that formulation can be stored for longer periods at room temperature. Tetrahydrocurcumin can be effectively administered by SLN for the treatment of diabetes. |
| first_indexed | 2024-03-12T01:47:17Z |
| format | Article |
| id | doaj.art-481edee39b0f4c7ea293651e2b31e792 |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-03-12T01:47:17Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-481edee39b0f4c7ea293651e2b31e7922023-09-09T04:54:42ZengElsevierSaudi Pharmaceutical Journal1319-01642023-09-01319101727Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitusJai Bharti Sharma0Shailendra Bhatt1Abhishek Tiwari2Varsha Tiwari3Manish Kumar4Ravinder Verma5Deepak Kaushik6Tarun Virmani7Girish Kumar8Omkulthom Al kamaly9Asmaa Saleh10Mohammed Khalid Parvez11Abdulsalam Alhalmi12M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Haryana, IndiaShrinathji Institute of Pharmacy, Shrinathji Society for Higher Education Upali Oden, Nathdwara, Rajasmand, Rajasthan, India; Corresponding authors.Pharmacy Academy, IFTM University, Lodhipur-Rajput, Moradabad 244102, U.P., IndiaPharmacy Academy, IFTM University, Lodhipur-Rajput, Moradabad 244102, U.P., IndiaSchool of Pharmaceutical Sciences, CT University, Ludhiana, Punjab, India; Corresponding authors.Department of Pharmaceutical Sciences, Chaudhary Bansi Lal, University, Bhiwani 127021, IndiaDepartment of Pharmaceutical Sciences, M.D. University, Rohtak, Haryana, IndiaSchool of Pharmaceutical Sciences, MVN University, Palwal, Haryana 121105, IndiaSchool of Pharmaceutical Sciences, MVN University, Palwal, Haryana 121105, IndiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O Box 84428, Riyadh 11671, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutics School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, IndiaIn the past, curcumin was the go-to medication for diabetes, but recent studies have shown that tetrahydrocurcumin is more effective. The problem is that it's not very soluble in water or very bioavailable. So, our research aims to increase the bioavailability and anti-diabetic efficacy of tetrahydrocurcumin in streptozotocin-induced diabetic rats by synthesizing tetrahydrocurcumin-loaded solid lipid nanoparticles. Box Behnken Design was employed for the optimization of tetrahydrocurcumin-loaded solid lipid nanoparticles (THC-SLNs). The optimal formulation was determined by doing an ANOVA to examine the relationship between the independent variables (drug-to-lipid ratio, surfactant concentration, and co-surfactant concentration) and the dependent variables (particle size, percent entrapment efficiency, and PDI). Particle size, PDI, and entrapment efficiency all showed statistical significance based on F-values and p-values. The optimized batch was prepared using a drug-to-lipid ratio (1:4.16), 1.21% concentration of surfactant, and 0.4775% co-surfactant (observed with a particle size of 147.1 nm, 83.58 ± 0.838 % entrapment efficiency, and 0.265 PDI, and the values were found very close with the predicted ones. As the THC peak vanishes from the DSC thermogram of the improved formulation, this indicates that the drug has been transformed from its crystalline form into its amorphous state. TEM analysis of optimized formulation demonstrated mono-dispersed particles with an average particle size of 145 nm which are closely related to zetasizer’s results. In-vitro release study of optimized formulation demonstrated burst release followed by sustained release up to 71.04% throughout 24 hrs. Increased bioavailability of the adjusted THC-SLN was found in an in vivo pharmacokinetics research with 9.47 folds higher AUC(0-t) compared to plain THC-suspension. Additionally, pharmacodynamic experiments of optimized formulation demonstrated a marked decrease in blood glucose level to 63.7% and increased body weight from 195.8 ± 7.223 to 231.2 ± 7.653 on the 28th day of the study and showed a better anti-diabetic effect than plain drug suspension. Results of stability studies revealed that formulation can be stored for longer periods at room temperature. Tetrahydrocurcumin can be effectively administered by SLN for the treatment of diabetes.http://www.sciencedirect.com/science/article/pii/S1319016423002220TetrahydrocurcuminBox-Behnken designSLNPharmacokinetic studyPharmacodynamic studySTZ-induced Diabetes Mellitus |
| spellingShingle | Jai Bharti Sharma Shailendra Bhatt Abhishek Tiwari Varsha Tiwari Manish Kumar Ravinder Verma Deepak Kaushik Tarun Virmani Girish Kumar Omkulthom Al kamaly Asmaa Saleh Mohammed Khalid Parvez Abdulsalam Alhalmi Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus Saudi Pharmaceutical Journal Tetrahydrocurcumin Box-Behnken design SLN Pharmacokinetic study Pharmacodynamic study STZ-induced Diabetes Mellitus |
| title | Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus |
| title_full | Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus |
| title_fullStr | Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus |
| title_full_unstemmed | Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus |
| title_short | Statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using Box Behnken design in the management of streptozotocin-induced diabetes mellitus |
| title_sort | statistical optimization of tetrahydrocurcumin loaded solid lipid nanoparticles using box behnken design in the management of streptozotocin induced diabetes mellitus |
| topic | Tetrahydrocurcumin Box-Behnken design SLN Pharmacokinetic study Pharmacodynamic study STZ-induced Diabetes Mellitus |
| url | http://www.sciencedirect.com/science/article/pii/S1319016423002220 |
| work_keys_str_mv | AT jaibhartisharma statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT shailendrabhatt statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT abhishektiwari statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT varshatiwari statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT manishkumar statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT ravinderverma statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT deepakkaushik statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT tarunvirmani statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT girishkumar statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT omkulthomalkamaly statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT asmaasaleh statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT mohammedkhalidparvez statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus AT abdulsalamalhalmi statisticaloptimizationoftetrahydrocurcuminloadedsolidlipidnanoparticlesusingboxbehnkendesigninthemanagementofstreptozotocininduceddiabetesmellitus |