Triterpenes Drug Delivery Systems, a Modern Approach for Arthritis Targeted Therapy
Abstract
:1. Introduction
Types of Arthritis
2. Animal Models of Arthritis
3. Triterpenoids with Activity on Osteoarthritis, Rheumatoid Arthritis and Gout
Triterpenoid | Cell Model/Animal Model/Dosage | Effects and Mode of Action | Ref. |
---|---|---|---|
Betulin (1) |
|
| [50] |
|
| [51] | |
|
| [49] | |
Mixture of α- and β-Boswellic acid (2 and 3) |
|
| [53] |
Madecassoside (4) |
|
| [55] |
Maslinic acid (5) |
|
| [58] |
|
| [56] |
4. Triterpene Drug Delivery Systems for Arthritis Targeted Therapy
4.1. Polymeric Nanoparticles
4.2. Polymeric Micelles
4.3. Vesicular Drug Delivery Systems
4.3.1. Liposomes
4.3.2. Niosomes
4.3.3. Phytosomes
Triterpenoid/Drug Delivery System | Preparation Method | Characterization | Cell/Animal Model | Results | Ref. |
---|---|---|---|---|---|
Ginsenoside CK (11) Folate-targeted liposomes (FA-LP-11) | LP-11 and FA-LP-11 prepared by the ethanol injection method with lipid phase:water phase ratio 1:10 (v/v) using EPC/Chol/TPGS/11 (32:16:8:7 mass ratio) or EPC/Chol/TPGS/DSPE-mPEG-FA/11 (32:16:6.4:1.6:7:7 mass ratio), respectively, in ethanol | FA-LP-11: size 249.13 ± 1.40 nm, PDI 0.18 ± 0.03, ZP −4.60 ± 0.80 mV; EE 93.33 ± 0.05%. LP-11: size 221.10 ± 2.80 nm, PDI 0.14 ± 0.05, ZP −3.30 ± 0.27 mV; EE 94.46 ± 0.22% | LPS-activated macrophages (RAW264.7 cells). AA in male SD rats (n = 6) |
| [88] |
Boswellic acids (mixture 2, 3, 8 and 9) Liposomes | Lipid film hydration using soy PC and cholesterol at 7:3 molar ratio plus boswellic acids followed by incorporation into 5% Carbopol 934 gel. | Size 324.45 nm; EE 85 ± 4.09% | Carrageenan-induced hind paw oedema in Wistar rats (n = 6) |
| [93] |
Celastrol (6) Selenium-deposited phytosomes (Se@6-PTs) | Melting-hydration followed by in situ reduction using soy PC (17 mg) and 6 (10 mg) at 1:1 stoichiometric ratio mixed with aqueous solution (10 mL) of sodium olate (25 mg), Na2SeO3 (10 mg) and excess of reduced GSH (which reduces Se4+ to Se that precipitates onto the surface of 6-PTs) | Size 126 nm (106.9 nm for CEL-PTs), PDI 0.228, ZP −25 mV; EE 98.85% | Caco-2 cells. AA in male SD rats (n = 5) |
| [94] |
Boswellic acids (mixture 2, 3, 8 and 9) Phytosomes | Formation of complex between boswellic acids and soy PC at 1:1 molar ratio followed by phytosome formation by mixing boswellic acids-PC complex and cholesterol at 7:3 molar ratio. Phytosomes were then incorporated into 5% Carbopol 934 gel. | Size 508.32 nm. | Carrageenan-induced hind paw oedema in Wistar rats (n = 6) |
| [93] |
Ursolic acid (12) Niosome gel (UANF) | 12-loaded niosomes prepared by film hydration using phospholipid (65 mg), cholesterol (12.3 mg), Span 60 (85 mg) and 12; niosomal-loaded gel formulation obtained by adding Carbopol 934 (1% w/w), PEG-400 (15% w/v) and TEA (0.5% w/v). | Size 665.45 nm; EE 92.74%. Transflux 17.25 μg/cm2/h | AA in Albino Wistar rats (n = 6) |
| [90] |
Boswellic acids (mixture 2, 3, 8 and 9) Niosomes | Reverse evaporation method using Span 60 and cholesterol at 7:3 molar ratio plus boswellic acids followed by incorporation into 5% Carbopol 934 gel. | Size 246.12 nm; EE 89 ± 5.32% | Carrageenan-induced hind paw oedema in Wistar rats (n = 6) |
| [93] |
Celastrol (6) Hyaluronic acid-functionalized bilosomes (HA@CEL-BLs) | Thin film hydration with drug/lipid ratio 1:10 using soy PC (80 mg), DOTAP (20 mg) and 6 (10 mg) hydrated with 10 mL of SDC solution (2 mg/mL), further coated with HA (10 mg) by electrostatic complexation with DOTAP. | Uncoated vesicles (6-BLs): size 95.3 nm, ZP 4.8 mV. Coated vesicles (HA@6-BLs): size 118.4 nm, ZP -34.2 mV. DL 8.15% EE 99.56% | Macrophages (RAW264.7 cells). AA in SD rats (n = 6). CAIA in DBA/1 mice (n = 6) |
| [87] |
4.4. Self-Emulsifying Drug Delivery Systems
4.5. Solid Lipid Nanoparticles and Nanostructured Lipid Carriers
Triterpenoid/Drug Delivery System | Preparation Method | Characterization | Cell/Animal Model | Results | Ref. |
---|---|---|---|---|---|
Self-emulsifying drug delivery systems (SEDDSs) | |||||
Oleanolic acid (13) Self-nanoemulsifyed drug delivery system (SNEDDS) | Prepared by mixing Sefsol®218 (lipid) with Cremophor®EL/Labrasol® (surfactant mixture) at 50:25:25 w/w, then adding 13 (20 mg/g) | Size 38.4 ± 0.2, PDI 0.055 | Male SD rats (n = 5) |
| [97] |
Oleanolic acid (13) Self-microemulsifying drug delivery system (SMEDDS) | Prepared by mixing Cremophor®EL (surfactant), ethanol (co-surfactant) and ethyl oleate (lipid) at 50:35:15 w/w with gentle stirring at 40 °C, then adding 13 (1% w/w) | Droplet size 49.7 nm DL 13.196 ± 0.328 mg/g | Male SD rats (n = 5) |
| [98] |
Celastrol (6) Solid and liquid SMEDDS | Liquid SMEDDS prepared by mixing ethyl oleate (lipid), OP-10 (surfactant) and Transcutol®P (co-surfactant) at 25:60:15 w/w, then adding 6 (10% w/w); Solid SMEDDS dispersible tablets prepared by wet granulation compression method using MCC KG 802 as solid adsorbent | Liquid SMEDDS: droplet size 23.17 ± 0.86, PDI 0.104 ± 0.009 Solid SMEDDS: droplet size 22.05 ± 0.86 1.56, PDI 0.113 ± 0.011 | Male SD rats (n = 6) |
| [99] |
Lipid nanoparticles (SLNs + NLCs) | |||||
Asiatic acid tromethamine salt (14) SLNs | Modified solvent injection method using 10 mg GMS (solid lipid) and 14 in 1.07 mL ethanol (oil phase) and 0.1 g poloxamer P188 (surfactant) in 20 mL water (aqueous phase); freeze-dried powder obtained by lyophilization using 10% lactose as cryoprotectant. | Size 237.6 ± 3.4 nm, ZP −35.9 ± 0.14 mV, DL 31.9 ± 2.9%, EE 64.4 ± 5.9% | Male SD rats (n = 6) |
| [104] |
Celastrol (6) + Indomethacin NLCs | Emulsification evaporation-solidification method using 6 (10 mg), Indomethacin (10 mg), Precirol®ATO-5 (solid lipid), Labrasol®ALF (liquid lipid) at 70:30, Cremophor®RH40 (surfactant), then adding 0.5% w/v Carbopol 940 to produce hydrogel | Size 26.92 ± 0.62 nm, DL 3.65 ± 0.05%, EE 96.56 ± 1.36% | AA in male SD rats (n = 6) |
| [108] |
Celastrol (6) CPP-coated NLCs (CPP-Cel-NLCs) | Solvent evaporation method using Precirol®ATO-5 (360 mg) as solid lipid and Labrafil®M 1944CS (120 mg) as liquid lipid at 3:1 w/w, SLT (60 mg) and TPGS (60 mg) as emulsifiers, 6 (30 mg) and 0.5% w/w F68 as surfactant. 6-NLCs coated with CPP (30 mg) at drug/CPP ratio 1:1 by electrostatic complexation | Uncoated (6-NLCs): size 102.4 ± 12.8 nm, PDI 0.129 ± 0.028, ZP −26.2 ± 2.71 mV, EE 74.04 ± 0.87%. Coated (CPP-6-NLCs): size 126.7 ± 9.2 nm, PDI 0.142 ± 0.03, ZP 28.7 ± 3.4 mV, EE 72.64 ± 1.37%. | Caco-2 cells. Male SD rats (n = 4). Beagle dogs (n = 6). |
| [107] |
Inorganic silica NPs | |||||
Celastrol (6) pH-responsive hollow MSNs (CEL@HMSNs-Cs) | Solid silica NPs (500 mg) (core) coated with mesoporous silica (shell) using TEOS (1.5 mL) and CTAB (0.75 mg) as stabilizer. Selective etching of the core by aqueous Na2CO3 (6 mol/L, 50 mL) at 80 °C produced hollow MSNs (100 mg), loaded with 6 (15 mg/mL, 10 mL) by passive diffusion and coated with chitosan (10% v/v) using GPTMS (100 mg) as cross-linker. | Coated (6 @HMSNs-Cs): mean size 290.17 nm, ZP 19.9 ± 0.7 mV, DL 24.3%; uncoated (6 @HMSNs): mean size 260.76 nm, ZP −9.5 ± 0.7 mV, DL 28.2%. BET pore diameter, pore volume (Vpore) and specific surface area (SBET) of empty MSNs (HMSNs) were 2.4 nm, 0.7668 cm3/g and 1006.8 m2/g, respectively, decreasing after drug loading (Vpore 0.2476 cm3/g and SBET 235.13 m2/g) and upon coating (Vpore 0.1205 cm3/g and SBET 52.816 m2/g) | IL-1β stimulated rat chondrocytes; MIA-induced knee OA in male SD rats (n = 6) |
| [109] |
4.6. Inorganic Silica Nanoparticles
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
Abbreviations
References
- Arthritis Foundation Arthritis by the Numbers. Book of Trusted Facts & Figures. 2020. Available online: https://www.arthritis.org/getmedia/73a9f02d-7f91-4084-91c3-0ed0b11c5814/abtn-2020-final.pdf (accessed on 15 February 2023).
- Senthelal, S.; Li, J.; Ardeshirzadeh, S.; Thomas, M. Arthritis. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022. [Google Scholar]
- Hunter, D.J.; Bierma-Zeinstra, S. Osteoarthritis. Lancet 2019, 393, 1745–1759. [Google Scholar] [CrossRef]
- Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (GBD 2019) Disease and Injury Burden 1990–2019. Seattle, United States of America: Institute for Health Metrics and Evaluation (IHME), 2020. Available online: https://ghdx.healthdata.org/record/ihme-data/gbd-2019-disease-and-injury-burden-1990-2019 (accessed on 16 September 2023).
- Faustino, C.; Pinheiro, L.; Duarte, N. Triterpenes as Potential Drug Candidates for Rheumatoid Arthritis Treatment. Life 2023, 13, 1514. [Google Scholar] [CrossRef]
- Furtado, N.A.J.C.; Pirson, L.; Edelberg, H.; Miranda, L.M.; Loira-Pastoriza, C.; Preat, V.; Larondelle, Y.; André, C.M. Pentacyclic triterpene bioavailability: An overview of in vitro and in vivo studies. Molecules 2017, 22, 400. [Google Scholar] [CrossRef]
- Scanu, A.; Luisetto, R.; Ramonda, R.; Spinella, P.; Sfriso, P.; Galozzi, P.; Oliviero, F. Anti-Inflammatory and Hypouricemic Effect of Bioactive Compounds: Molecular Evidence and Potential Application in the Management of Gout. Curr. Issues Mol. Biol. 2022, 44, 5173–5190. [Google Scholar] [CrossRef]
- Patra, J.K.; Das, G.; Fraceto, L.F.; Vangelie, E.; Campos, R.; Rodriguez, P.; Susana, L.; Torres, A.; Armando, L.; Torres, D.; et al. Nano based drug delivery systems: Recent developments and future prospects. J. Nanobiotechnol. 2018, 16, 71. [Google Scholar] [CrossRef]
- Rahman, M.; Beg, S.; Verma, A.; Al Abbasi, F.A.; Anwar, F.; Saini, S.; Akhter, S.; Kumar, V. Phytoconstituents as pharmacotherapeutics in rheumatoid arthritis: Challenges and scope of nano/submicromedicine in its effective delivery. J. Pharm. Pharmacol. 2017, 69, 1–14. [Google Scholar] [CrossRef]
- O’Neill, T.W.; McCabe, P.S.; McBeth, J. Update on the epidemiology, risk factors and disease outcomes of osteoarthritis. Best Pract. Res. Clin. Rheumatol. 2018, 32, 312–326. [Google Scholar] [CrossRef]
- Aubourg, G.; Rice, S.J.; Bruce-Wootton, P.; Loughlin, J. Genetics of osteoarthritis. Osteoarthr. Cartil. 2022, 30, 636–649. [Google Scholar] [CrossRef]
- Boer, C.G.; Hatzikotoulas, K.; Southam, L.; Stefánsdóttir, L.; Zhang, Y.; Coutinho de Almeida, R.; Wu, T.T.; Zheng, J.; Hartley, A.; Teder-Laving, M.; et al. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell 2021, 184, 4784–4818. [Google Scholar] [CrossRef] [PubMed]
- Attur, M.; Zhou, H.; Samuels, J.; Krasnokutsky, S.; Yau, M.; Scher, J.U.; Doherty, M.; Wilson, A.G.; Bencardino, J.; Hochberg, M.; et al. Interleukin 1 receptor antagonist (IL1RN) gene variants predict radiographic severity of knee osteoarthritis and risk of incident disease. Ann. Rheum. Dis. 2019, 1, 400–407. [Google Scholar] [CrossRef] [PubMed]
- Chow, Y.; Chin, K. The role of inflammation in the pathogenesis of osteoarthritis. Mediat. Inflammatio 2020, 2020, 8293921. [Google Scholar] [CrossRef]
- Berenbaum, F.; Wallace, I.J.; Lieberman, D.E.; Felson, D.T. Modern-day environmental factors in the pathogenesis of osteoarthritis. Nat. Rev. Rheumatol. 2018, 14, 674–681. [Google Scholar] [CrossRef]
- Hall, M.; Castelein, B.; Wittoek, R.; Calders, P.; Van Ginckel, A. Diet-induced weight loss alone or combined with exercise in overweight or obese people with knee osteoarthritis: A systematic review and meta-analysis. Semin. Arthritis Rheum. 2019, 48, 765–777. [Google Scholar] [CrossRef]
- Da Costa, B.R.; Pereira, T.V.; Saadat, P.; Rudnicki, M.; Iskander, S.M.; Bodmer, N.S.; Bobos, P.; Gao, L.; Kiyomoto, H.D.; Montezuma, T.; et al. Effectiveness and safety of non-steroidal anti-inflammatory drugs and opioid treatment for knee and hip osteoarthritis: Network meta-analysis. BMJ 2021, 375, n2321. [Google Scholar] [CrossRef]
- Migliorini, F.; Driessen, A.; Quack, V.; Sippel, N.; Cooper, B.; Mansy, Y.E.; Tingart, M.; Eschweiler, J. Comparison between intra-articular infiltrations of placebo, steroids, hyaluronic and PRP for knee osteoarthritis: A Bayesian network meta-analysis. Arch. Orthop. Trauma Surg. 2021, 141, 1473–1490. [Google Scholar] [CrossRef]
- Szponder, T.; Latalski, M.; Danielewicz, A.; Krać, K.; Kozera, A.; Drzewiecka, B.; Nguyen Ngoc, D.; Dobko, D.; Wessely-Szponder, J. Osteoarthritis: Pathogenesis, Animal Models, and New Regenerative Therapies. J. Clin. Med. 2022, 12, 5. [Google Scholar] [CrossRef]
- Zhu, X.; Wu, D.; Sang, L.; Wang, Y.; Shen, Y.; Zhuang, X.; Chu, M.; Jiang, L. Comparative effectiveness of glucosamine, chondroitin, acetaminophen or celecoxib for the treatment of knee and/or hip osteoarthritis: A network meta-analysis. Clin. Exp. Rheumatol. 2018, 36, 595–602. [Google Scholar]
- Smolen, J.S.; Aletaha, D.; McInnes, I.B. Rheumatoid arthritis. Lancet 2016, 388, 2023–2038. [Google Scholar] [CrossRef]
- Smolen, J.S.; Aletaha, D.; Barton, A.; Burmester, G.R.; Emery, P.; Firestein, G.S.; Kavanaugh, A.; McInnes, I.B.; Solomon, D.H.; Strand, V.; et al. Rheumatoid arthritis. Nat. Rev. Dis. Prim. 2018, 4, 18001. [Google Scholar] [CrossRef] [PubMed]
- Padyukov, L. Genetics of rheumatoid arthritis. Semin. Immunopathol. 2022, 44, 47–62. [Google Scholar] [CrossRef] [PubMed]
- Scherer, H.U.; Häupl, T.; Burmester, G.R. The etiology of rheumatoid arthritis. J. Autoimmun. 2020, 110, 102400. [Google Scholar] [CrossRef] [PubMed]
- Firestein, G.S.; McInnes, I.B. Immunopathogenesis of Rheumatoid Arthritis. Immunity 2017, 46, 183–196. [Google Scholar] [CrossRef] [PubMed]
- Frisell, T.; Holmqvist, M.; Källberg, H.; Klareskog, L.; Alfredsson, L.; Askling, J. Familial risks and heritability of rheumatoid arthritis: Role of rheumatoid factor/anti-citrullinated protein antibody status, number and type of affected relatives, sex, and age. Arthritis Rheum. 2013, 65, 2773–2782. [Google Scholar] [CrossRef] [PubMed]
- Schäfer, C.; Keyßer, G. Lifestyle Factors and Their Influence on Rheumatoid Arthritis: A Narrative Review. J. Clin. Med. 2022, 11, 7179. [Google Scholar] [CrossRef] [PubMed]
- Alivernini, S.; Firestein, G.S.; McInnes, I.B. The pathogenesis of rheumatoid arthritis. Immunity 2022, 55, 2255–2270. [Google Scholar] [CrossRef] [PubMed]
- Alivernini, S.; Tolusso, B.; Fedele, A.L.; Di Mario, C.; Ferraccioli, G.; Gremese, E. The B side of rheumatoid arthritis pathogenesis. Pharmacol. Res. 2019, 149, 104465. [Google Scholar] [CrossRef]
- Guo, C.; Fu, R.; Wang, S.; Huang, Y.; Li, X.; Zhou, M.; Zhao, J.; Yang, N. NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis. Clin. Exp. Immunol. 2018, 194, 231–243. [Google Scholar] [CrossRef]
- Aletaha, D.; Smolen, J.S. Diagnosis and Management of Rheumatoid Arthritis: A Review. JAMA—J. Am. Med. Assoc. 2018, 320, 1360–1372. [Google Scholar] [CrossRef]
- Bodofsky, S.; Merriman, T.R.; Thomas, T.J.; Schlesinger, N. Advances in our understanding of gout as an auto-inflammatory disease. Semin. Arthritis Rheum. 2020, 50, 1089–1100. [Google Scholar] [CrossRef]
- Dalbeth, N.; Gosling, A.L.; Gaffo, A.; Abhishek, A. Gout. Lancet 2021, 397, 1843–1855. [Google Scholar] [CrossRef]
- Kuo, C.F.; Grainge, M.J.; Zhang, W.; Doherty, M. Global epidemiology of gout: Prevalence, incidence and risk factors. Nat. Rev. Rheumatol. 2015, 11, 649–662. [Google Scholar] [CrossRef] [PubMed]
- Keenan, R.T. The biology of urate. Semin. Arthritis Rheum. 2020, 50, S2–S10. [Google Scholar] [CrossRef] [PubMed]
- Pillinger, M.H.; Mandell, B.F. Therapeutic approaches in the treatment of gout. Semin. Arthritis Rheum. 2020, 50, S24–S30. [Google Scholar] [CrossRef] [PubMed]
- Wechalekar, M.D.; Vinik, O.; Moi, J.H.Y.; Sivera, F.; Van Echteld, I.A.A.M.; Van Durme, C.; Falzon, L.; Bombardier, C.; Carmona, L.; Aletaha, D.; et al. The efficacy and safety of treatments for acute gout: Results from a series of systematic literature reviews including cochrane reviews on intraarticular glucocorticoids, colchicine, nonsteroidal antiinflammatory drugs, and interleukin-1 inhibitors. J. Rheumatol. 2014, 41, 15–25. [Google Scholar] [CrossRef] [PubMed]
- Sivera, F.; Wechalekar, M.D.; Andrés, M.; Buchbinder, R.; Carmona, L. Interleukin-1 inhibitors for acute gout. Cochrane Database Syst. Rev. 2014, 2014, CD009993. [Google Scholar] [CrossRef]
- Jenkins, C.; Hwang, J.H.; Kopp, J.B.; Winkler, C.A.; Cho, S.K. Review of Urate-Lowering Therapeutics: From the Past to the Future. Front. Pharmacol. 2022, 13, 925219. [Google Scholar] [CrossRef]
- Lipsky, P.E.; Calabrese, L.H.; Kavanaugh, A.; Sundy, J.S.; Wright, D.; Wolfson, M.; Becker, M.A. Pegloticase immunogenicity: The relationship between efficacy and antibody development in patients treated for refractory chronic gout. Arthritis Res. Ther. 2014, 16, R60. [Google Scholar] [CrossRef]
- Bessis, N.; Decker, P.; Assier, E.; Semerano, L.; Boissier, M.C. Arthritis models: Usefulness and interpretation. Semin. Immunopathol. 2017, 39, 469–486. [Google Scholar] [CrossRef]
- Chapman, J.H.; Ghosh, D.; Attari, S.; Ude, C.C.; Laurencin, C.T. Animal Models of Osteoarthritis: Updated Models and Outcome Measures 2016–2023. Regen. Eng. Transl. Med. 2023. [Google Scholar] [CrossRef]
- McNamee, K.; Williams, R.; Seed, M. Animal models of rheumatoid arthritis: How informative are they? Eur. J. Pharmacol. 2015, 759, 278–286. [Google Scholar] [CrossRef]
- Patil, T.; Soni, A.; Acharya, S. A brief review on in vivo models for Gouty Arthritis. Metab. Open 2021, 11, 100100. [Google Scholar] [CrossRef] [PubMed]
- Zhao, T.; Xie, Z.; Xi, Y.; Liu, L.; Li, Z.; Qin, D. How to Model Rheumatoid Arthritis in Animals: From Rodents to Non-Human Primates. Front. Immunol. 2022, 13, 887460. [Google Scholar] [CrossRef] [PubMed]
- Choudhary, N.; Bhatt, L.K.; Prabhavalkar, K.S. Experimental animal models for rheumatoid arthritis. Immunopharmacol. Immunotoxicol. 2018, 40, 193–200. [Google Scholar] [CrossRef] [PubMed]
- Oliveira-Costa, J.F.; Meira, C.S.; das Neves, M.V.G.; Dos Reis, B.P.Z.C.; Soares, M.B.P. Anti-Inflammatory Activities of Betulinic Acid: A Review. Front. Pharmacol. 2022, 13, 883857. [Google Scholar] [CrossRef] [PubMed]
- Renda, G.; Gökkaya, İ.; Şöhretoğlu, D. Immunomodulatory properties of triterpenes. Phytochem. Rev. 2022, 21, 537–563. [Google Scholar] [CrossRef] [PubMed]
- Ra, H.J.; Lee, H.J.; Jo, H.S.; Nam, D.C.; Lee, Y.B.; Kang, B.H.; Moon, D.K.; Kim, D.H.; Lee, C.J.; Hwang, S.C. Betulin suppressed interleukin-1β-induced gene expression, secretion and proteolytic activity of matrix metalloproteinase in cultured articular chondrocytes and production of matrix metalloproteinase in the knee joint of rat. Korean J. Physiol. Pharmacol. 2017, 21, 19–26. [Google Scholar] [CrossRef] [PubMed]
- Ren, C.; Jin, J.; Hu, W.; Chen, Q.; Yang, J.; Wu, Y.; Zhou, Y.; Sun, L.; Gao, W.; Zhang, X.; et al. Betulin Alleviates the Inflammatory Response in Mouse Chondrocytes and Ameliorates Osteoarthritis via AKT/Nrf2/HO-1/NF-κB Axis. Front. Pharmacol. 2021, 12, 754038. [Google Scholar] [CrossRef]
- Su, C.H.; Lin, C.Y.; Tsai, C.H.; Lee, H.P.; Lo, L.C.; Huang, W.C.; Wu, Y.C.; Hsieh, C.L.; Tang, C.H. Betulin suppresses TNF-α and IL-1β production in osteoarthritis synovial fibroblasts by inhibiting the MEK/ERK/NF-κB pathway. J. Funct. Foods 2021, 86, 104729. [Google Scholar] [CrossRef]
- Ammon, H.P.T. Boswellic acids and their role in chronic inflammatory diseases. Adv. Exp. Med. Biol. 2016, 928, 291–327. [Google Scholar] [CrossRef]
- Sabina, E.P.; Indu, H.; Rasool, M. Efficacy of boswellic acid on lysosomal acid hydrolases, lipid peroxidation and anti-oxidant status in gouty arthritic mice. Asian Pac. J. Trop. Biomed. 2012, 2, 128–133. [Google Scholar] [CrossRef]
- Wang, T.; Wei, Z.; Dou, Y.; Yang, Y.; Leng, D.; Kong, L.; Dai, Y.; Xia, Y. Intestinal interleukin-10 mobilization as a contributor to the anti-arthritis effect of orally administered madecassoside: A unique action mode of saponin compounds with poor bioavailability. Biochem. Pharmacol. 2015, 94, 30–38. [Google Scholar] [CrossRef]
- Lu, X.; Zeng, R.; Lin, J.; Hu, J.; Rong, Z.; Xu, W.; Liu, Z.; Zeng, W. Pharmacological basis for use of madecassoside in gouty arthritis: Anti-inflammatory, anti-hyperuricemic, and NLRP3 inhibition. Immunopharmacol. Immunotoxicol. 2019, 41, 277–284. [Google Scholar] [CrossRef]
- Fukumitsu, S.; Villareal, M.O.; Aida, K.; Hino, A.; Hori, N.; Isoda, H.; Naito, Y. Maslinic acid in olive fruit alleviates mild knee joint pain and improves quality of life by promoting weight loss in the elderly. J. Clin. Biochem. Nutr. 2016, 59, 220–225. [Google Scholar] [CrossRef]
- Fukumitsu, S.; Villareal, M.O.; Fujitsuka, T.; Aida, K.; Isoda, H. Anti-inflammatory and anti-arthritic effects of pentacyclic triterpenoids maslinic acid through NF-κB inactivation. Mol. Nutr. Food Res. 2016, 60, 399–409. [Google Scholar] [CrossRef]
- Shimazu, K.; Fukumitsu, S.; Ishijima, T.; Toyoda, T.; Nakai, Y.; Abe, K.; Aida, K.; Okada, S.; Hino, A. The Anti-Arthritis Effect of Olive-Derived Maslinic Acid in Mice is due to its Promotion of Tissue Formation and Its Anti-Inflammatory Effects. Mol. Nutr. Food Res. 2019, 63, e1800543. [Google Scholar] [CrossRef]
- Dudics, S.; Venkatesha, S.H.; Moudgil, K.D. The micro-RNA expression profiles of autoimmune arthritis reveal novel biomarkers of the disease and therapeutic response. Int. J. Mol. Sci. 2018, 19, 2293. [Google Scholar] [CrossRef] [PubMed]
- Li, S.; Su, J.; Cai, W.; Liu, J.X. Nanomaterials Manipulate Macrophages for Rheumatoid Arthritis Treatment. Front. Pharmacol. 2021, 12, 699245. [Google Scholar] [CrossRef] [PubMed]
- Jeong, M.; Park, J.H. Nanomedicine for the Treatment of Rheumatoid Arthritis. Mol. Pharm. 2021, 18, 539–549. [Google Scholar] [CrossRef] [PubMed]
- Albuquerque, J.; Moura, C.C.; Sarmento, B.; Reis, S. Solid lipid nanoparticles: A potential multifunctional approach towards rheumatoid arthritis theranostics. Molecules 2015, 20, 11103–11118. [Google Scholar] [CrossRef] [PubMed]
- Lyu, J.; Wang, L.; Bai, X.; Du, X.; Wei, J.; Wang, J.; Lin, Y.; Chen, Z.; Liu, Z.; Wu, J.; et al. Treatment of Rheumatoid Arthritis by Serum Albumin Nanoparticles Coated with Mannose to Target Neutrophils. ACS Appl. Mater. Interfaces 2021, 13, 266–276. [Google Scholar] [CrossRef]
- Yu, C.; Li, X.; Hou, Y.; Meng, X.; Wang, D.; Liu, J.; Sun, F.; Li, Y. Hyaluronic acid coated acid-sensitive nanoparticles for targeted therapy of adjuvant-induced arthritis in rats. Molecules 2019, 24, 146. [Google Scholar] [CrossRef] [PubMed]
- Wu, Z.; Xu, K.; Min, J.; Chen, M.; Shen, L.; Xu, J.; Jiang, Q.; Han, G.; Pan, L.; Li, H. Folate-conjugated hydrophobicity modified glycol chitosan nanoparticles for targeted delivery of methotrexate in rheumatoid arthritis. J. Appl. Biomater. Funct. Mater. 2020, 18, 2280800020962629. [Google Scholar] [CrossRef] [PubMed]
- Zhao, J.; Zhang, X.; Sun, X.; Zhao, M.; Yu, C.; Lee, R.J.; Sun, F.; Zhou, Y.; Li, Y.; Teng, L. Dual-functional lipid polymeric hybrid pH-responsive nanoparticles decorated with cell penetrating peptide and folate for therapy against rheumatoid arthritis. Eur. J. Pharm. Biopharm. 2018, 130, 39–47. [Google Scholar] [CrossRef] [PubMed]
- Yang, M.; Ding, J.; Feng, X.; Chang, F.; Wang, Y.; Gao, Z.; Zhuang, X.; Chen, X. Scavenger receptor-mediated targeted treatment of collagen-induced arthritis by dextran sulfate-methotrexate prodrug. Theranostics 2017, 7, 97–105. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Q.; Dehaini, D.; Zhang, Y.; Zhou, J.; Chen, X.; Zhang, L.; Fang, R.H.; Gao, W.; Zhang, L. Neutrophil membrane-coated nanoparticles inhibit synovial inflammation and alleviate joint damage in inflammatory arthritis. Nat. Nanotechnol. 2018, 13, 1182–1190. [Google Scholar] [CrossRef]
- Li, R.; He, Y.; Zhu, Y.; Jiang, L.; Zhang, S.; Qin, J.; Wu, Q.; Dai, W.; Shen, S.; Pang, Z.; et al. Route to Rheumatoid Arthritis by Macrophage-Derived Microvesicle-Coated Nanoparticles. Nano Lett. 2019, 19, 124–134. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Rao, P.; Qian, H.; Shi, Y.; Chen, S.; Lan, J.; Mu, D.; Chen, R.; Zhang, X.; Deng, C.; et al. Regulatory Fibroblast-Like Synoviocytes Cell Membrane Coated Nanoparticles: A Novel Targeted Therapy for Rheumatoid Arthritis. Adv. Sci. 2023, 10, 2204998. [Google Scholar] [CrossRef] [PubMed]
- Faustino, C.; Pinheiro, L. Lipid systems for the delivery of amphotericin B in antifungal therapy. Pharmaceutics 2020, 12, 29. [Google Scholar] [CrossRef]
- Deng, C.; Zhang, Q.; He, P.; Zhou, B.; He, K.; Sun, X.; Lei, G.; Gong, T.; Zhang, Z. Targeted apoptosis of macrophages and osteoclasts in arthritic joints is effective against advanced inflammatory arthritis. Nat. Commun. 2021, 12, 2174. [Google Scholar] [CrossRef]
- Gong, T.; Zhang, P.; Deng, C.; Xiao, Y.; Gong, T.; Zhang, Z. An effective and safe treatment strategy for rheumatoid arthritis based on human serum albumin and Kolliphor® HS 15. Nanomedicine 2019, 14, 2169–2187. [Google Scholar] [CrossRef]
- Ansari, M.M.; Ahmad, A.; Kumar, A.; Alam, P.; Khan, T.H.; Jayamurugan, G.; Raza, S.S.; Khan, R. Aminocellulose-grafted-polycaprolactone coated gelatin nanoparticles alleviate inflammation in rheumatoid arthritis: A combinational therapeutic approach. Carbohydr. Polym. 2021, 258, 117600. [Google Scholar] [CrossRef] [PubMed]
- Bairwa, K.; Jachak, S.M. Nanoparticle formulation of 11-keto-β-boswellic acid (KBA): Anti-inflammatory activity and in vivo pharmacokinetics. Pharm. Biol. 2016, 54, 2909–2916. [Google Scholar] [CrossRef] [PubMed]
- Bairwa, K.; Jachak, S.M. Development and optimisation of 3-Acetyl-11-keto-β-boswellic acid loaded poly-lactic-co-glycolic acid-nanoparticles with enhanced oral bioavailability and in-vivo anti-inflammatory activity in rats. J. Pharm. Pharmacol. 2015, 67, 1188–1197. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.; Zhu, H.; Zhou, W.; Ye, Q. Anti-inflammatory and anti-gouty-arthritic effect of free Ginsenoside Rb1 and nano Ginsenoside Rb1 against MSU induced gouty arthritis in experimental animals. Chem. Biol. Interact. 2020, 332, 109285. [Google Scholar] [CrossRef] [PubMed]
- Yu, C.; Liu, H.; Guo, C.; Chen, Q.; Su, Y.; Guo, H.; Hou, X.; Zhao, F.; Fan, H.; Xu, H.; et al. Dextran sulfate-based MMP-2 enzyme-sensitive SR-A receptor targeting nanomicelles for the treatment of rheumatoid arthritis. Drug Deliv. 2022, 29, 454–465. [Google Scholar] [CrossRef] [PubMed]
- Zhao, X.; Huang, C.; Su, M.; Ran, Y.; Wang, Y.; Yin, Z. Reactive Oxygen Species–Responsive Celastrol-Loaded: Bilirubin Nanoparticles for the Treatment of Rheumatoid Arthritis. AAPS J. 2021, 24, 14. [Google Scholar] [CrossRef]
- An, L.; Li, Z.; Shi, L.; Wang, L.; Wang, Y.; Jin, L.; Shuai, X.; Li, J. Inflammation-Targeted Celastrol Nanodrug Attenuates Collagen-Induced Arthritis through NF-κB and Notch1 Pathways. Nano Lett. 2020, 20, 7728–7736. [Google Scholar] [CrossRef]
- Goel, A.; Ahmad, F.J.; Singh, R.M.; Singh, G.N. 3-Acetyl-11-keto-β-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity. J. Pharm. Pharmacol. 2010, 62, 273–278. [Google Scholar] [CrossRef]
- Aburahma, M.H. Bile salts-containing vesicles: Promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines. Drug Deliv. 2016, 23, 1847–1867. [Google Scholar] [CrossRef]
- Milan, A.; Mioc, A.; Prodea, A.; Mioc, M.; Buzatu, R.; Ghiulai, R.; Racoviceanu, R.; Caruntu, F.; Şoica, C. The Optimized Delivery of Triterpenes by Liposomal Nanoformulations: Overcoming the Challenges. Int. J. Mol. Sci. 2022, 23, 1140. [Google Scholar] [CrossRef]
- Ren, Y.; Nie, L.; Zhu, S.; Zhang, X. Nanovesicles-Mediated Drug Delivery for Oral Bioavailability Enhancement. Int. J. Nanomed. 2022, 17, 4861–4877. [Google Scholar] [CrossRef] [PubMed]
- Ahmad, J.; Singhal, M.; Amin, S.; Rizwanullah, M.; Akhter, S.; Kamal, M.A.; Haider, N.; Midoux, P.; Pichon, C. Bile Salt Stabilized Vesicles (Bilosomes): A Novel Nano-Pharmaceutical Design for Oral Delivery of Proteins and Peptides. Curr. Pharm. Des. 2017, 23, 1575–1588. [Google Scholar] [CrossRef] [PubMed]
- Elkomy, M.H.; Alruwaili, N.K.; Elmowafy, M.; Shalaby, K.; Zafar, A.; Ahmad, N.; Alsalahat, I.; Ghoneim, M.M.; Eissa, E.M.; Eid, H.M. Surface-Modified Bilosomes Nanogel Bearing a Natural Plant Alkaloid for Safe Management of Rheumatoid Arthritis Inflammation. Pharmaceutics 2022, 14, 563. [Google Scholar] [CrossRef] [PubMed]
- Yang, H.; Liu, Z.; Song, Y.; Hu, C. Hyaluronic acid-functionalized bilosomes for targeted delivery of tripterine to inflamed area with enhancive therapy on arthritis. Drug Deliv. 2019, 26, 820–830. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Han, S.; Cui, G.; Xue, B.; Li, J.; Man, Y.; Zhang, H.; Teng, L. Oral liposomes encapsulating ginsenoside compound K for rheumatoid arthritis therapy. Int. J. Pharm. 2023, 643, 123247. [Google Scholar] [CrossRef] [PubMed]
- Seleci, D.; Seleci, M.; Walter, J.G.; Stahl, F.; Scheper, T. Niosomes as nanoparticular drug carriers: Fundamentals and recent applications. J. Nanomater. 2016, 2016, 7372306. [Google Scholar] [CrossRef]
- Jamal, M.; Imam, S.S.; Aqil, M.; Amir, M.; Mir, S.R.; Mujeeb, M. Transdermal potential and anti-arthritic efficacy of ursolic acid from niosomal gel systems. Int. Immunopharmacol. 2015, 29, 361–369. [Google Scholar] [CrossRef] [PubMed]
- Lu, M.; Qiu, Q.; Luo, X.; Liu, X.; Sun, J.; Song, Y. Phyto-phospholipid complexes (phytosomes): A novel strategy to improve the bioavailability of active constituents. Asian J. Pharm. Sci. 2019, 14, 265–274. [Google Scholar] [CrossRef]
- Freag, M.S.; Saleh, W.M.; Abdallah, O.Y. Self-assembled phospholipid-based phytosomal nanocarriers as promising platforms for improving oral bioavailability of the anticancer celastrol. Int. J. Pharm. 2018, 535, 18–26. [Google Scholar] [CrossRef]
- Sharma, A.; Gupta, N.K.; Dixit, V.K. Complexation with phosphatidyl choline as a strategy for absorption enhancement of boswellic acid. Drug Deliv. 2010, 17, 587–595. [Google Scholar] [CrossRef]
- Zhu, S.; Luo, C.; Feng, W.; Li, Y.; Zhu, M.; Sun, S.; Zhang, X. Selenium-deposited tripterine phytosomes ameliorate the antiarthritic efficacy of the phytomedicine via a synergistic sensitization. Int. J. Pharm. 2020, 578, 119104. [Google Scholar] [CrossRef] [PubMed]
- Krstic, M.; Medarevic, D.; Duris, J.; Ibric, S. Self-nanoemulsifying drug delivery systems (SNEDDS) and self-microemulsifying drug delivery systems (SMEDDS) as lipid nanocarriers for improving dissolution rate and bioavailability of poorly soluble drugs. In Lipid Nanocarriers for Drug Targeting; Elsevier: Amsterdam, The Netherlands, 2018; pp. 473–508. [Google Scholar]
- Maji, I.; Mahajan, S.; Sriram, A.; Medtiya, P.; Vasave, R.; Khatri, D.K.; Kumar, R.; Singh, S.B.; Madan, J.; Singh, P.K. Solid self emulsifying drug delivery system: Superior mode for oral delivery of hydrophobic cargos. J. Control. Release 2021, 337, 646–660. [Google Scholar] [CrossRef] [PubMed]
- Xi, J.; Chang, Q.; Chan, C.K.; Meng, Z.Y.; Wang, G.N.; Sun, J.B.; Wang, Y.T.; Tong, H.H.Y.; Zheng, Y. Formulation development and bioavailability evaluation of a self-nanoemulsified drug delivery system of oleanolic acid. AAPS PharmSciTech 2009, 10, 172–182. [Google Scholar] [CrossRef] [PubMed]
- Yang, R.; Huang, X.; Dou, J.; Zhai, G.; Lequn, S. Self-microemulsifying drug delivery system for improved oral bioavailability of oleanolic acid: Design and evaluation. Int. J. Nanomed. 2013, 8, 2917–2926. [Google Scholar] [CrossRef]
- Qi, X.; Qin, J.; Ma, N.; Chou, X.; Wu, Z. Solid self-microemulsifying dispersible tablets of celastrol: Formulation development, charaterization and bioavailability evaluation. Int. J. Pharm. 2014, 472, 40–47. [Google Scholar] [CrossRef] [PubMed]
- Gordillo-Galeano, A.; Mora-Huertas, C.E. Solid lipid nanoparticles and nanostructured lipid carriers: A review emphasizing on particle structure and drug release. Eur. J. Pharm. Biopharm. 2018, 133, 285–308. [Google Scholar] [CrossRef] [PubMed]
- Viegas, C.; Patrício, A.B.; Prata, J.M.; Nadhman, A.; Chintamaneni, P.K.; Fonte, P. Solid Lipid Nanoparticles vs. Nanostructured Lipid Carriers: A Comparative Review. Pharmaceutics 2023, 15, 1593. [Google Scholar] [CrossRef] [PubMed]
- Anita, C.; Munira, M.; Mural, Q.; Shaily, L. Topical nanocarriers for management of Rheumatoid Arthritis: A review. Biomed. Pharmacother. 2021, 141, 111880. [Google Scholar] [CrossRef]
- Wang, T.; Luo, Y. Biological fate of ingested lipid-based nanoparticles: Current understanding and future directions. Nanoscale 2019, 11, 11048–11063. [Google Scholar] [CrossRef]
- Lingling, G.; Yuan, Z.; Weigen, L. Preparation, optimization, characterization and in vivo pharmacokinetic study of asiatic acid tromethamine salt-loaded solid lipid nanoparticles. Drug Dev. Ind. Pharm. 2016, 42, 1325–1333. [Google Scholar] [CrossRef]
- Zhou, L.; Zhang, Z.; He, J.; Du, M.; Wu, Q.; Chen, Y. Preparation of tripterine nanostructured lipid carriers and their absorption in rat intestine. Pharmazie 2012, 67, 304–310. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Zhang, T.; Zhou, X.; Liu, H.; Sun, H.U.A.; Ma, Z.; Wu, B. Enhancement of Oral Bioavailability of Tripterine through Lipid Nanospheres: Preparation, Characterization, and Absorption. J. Pharm. Sci. 2014, 103, 1711–1719. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.; Yuan, L.; Zhou, L.; Zhang, Z.H.; Cao, W.; Wu, Q. Effect of cell-penetrating peptide-coated nanostructured lipid carriers on the oral absorption of tripterine. Int. J. Nanomed. 2012, 7, 4581–4591. [Google Scholar] [CrossRef]
- Kang, Q.; Liu, J.; Zhao, Y.; Liu, X.; Liu, X.Y.; Wang, Y.J.; Mo, N.L.; Wu, Q. Transdermal delivery system of nanostructured lipid carriers loaded with Celastrol and Indomethacin: Optimization, characterization and efficacy evaluation for rheumatoid arthritis. Artif. Cells Nanomed. Biotechnol. 2018, 46, S585–S597. [Google Scholar] [CrossRef] [PubMed]
- Jin, T.; Wu, D.; Liu, X.M.; Xu, J.T.; Ma, B.J.; Ji, Y.; Jin, Y.Y.; Wu, S.Y.; Wu, T.; Ma, K. Intra-articular delivery of celastrol by hollow mesoporous silica nanoparticles for pH-sensitive anti-inflammatory therapy against knee osteoarthritis. J. Nanobiotechnol. 2020, 18, 94. [Google Scholar] [CrossRef] [PubMed]
- Sivamaruthi, B.S.; Thangaleela, S.; Kesika, P.; Suganthy, N.; Chaiyasut, C. Mesoporous Silica-Based Nanoplatforms Are Theranostic Agents for the Treatment of Inflammatory Disorders. Pharmaceutics 2023, 15, 439. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Li, N.; Pan, W.; Yu, Z.; Yang, L.; Tang, B. Hollow mesoporous silica nanoparticles with tunable structures for controlled drug delivery. ACS Appl. Mater. Interfaces 2017, 9, 2123–2129. [Google Scholar] [CrossRef]
- Win, Y.Y.; Charoenkanburkang, P.; Limprasutr, V.; Rodsiri, R.; Pan, Y.; Buranasudja, V.; Luckanagul, J.A. In vivo biocompatible self-assembled nanogel based on hyaluronic acid for aqueous solubility and stability enhancement of asiatic acid. Polymers 2021, 13, 4071. [Google Scholar] [CrossRef]
- Wang, L.; Lu, A.P.; Yu, Z.L.; Wong, R.N.S.; Bian, Z.X.; Kwok, H.H.; Yue, P.Y.K.; Zhou, L.M.; Chen, H.; Xu, M.; et al. The melanogenesis-inhibitory effect and the percutaneous formulation of ginsenoside Rb1. AAPS PharmSciTech 2014, 15, 1252–1262. [Google Scholar] [CrossRef]
- Zhang, Y.; Tong, D.; Che, D.; Pei, B.; Xia, X.; Yuan, G.; Jin, X. Ascorbyl palmitate/D-α-tocopheryl polyethylene glycol 1000 succinate monoester mixed micelles for prolonged circulation and targeted delivery of compound K for antilung cancer therapy in vitro and in vivo. Int. J. Nanomed. 2017, 12, 605–614. [Google Scholar] [CrossRef]
- Claude, B.; Morin, P.; Lafosse, M.; Andre, P. Evaluation of apparent formation constants of pentacyclic triterpene acids complexes with derivatized β- and γ-cyclodextrins by reversed phase liquid chromatography. J. Chromatogr. A 2004, 1049, 37–42. [Google Scholar] [CrossRef] [PubMed]
- Castellano, J.; Ramos-Romero, S.; Perona, J. Oleanolic Acid: Extraction, Characterization and Biological Activity. Nutrients 2022, 14, 623. [Google Scholar] [CrossRef] [PubMed]
- Song, S.; Gao, K.; Niu, R.; Yi, W.; Zhang, J.; Gao, C.; Yang, B.; Liao, X. Binding behavior, water solubility and in vitro cytotoxicity of inclusion complexes between ursolic acid and amino-appended β-cyclodextrins. J. Mol. Liq. 2019, 296, 111993. [Google Scholar] [CrossRef]
Triterpenoid/Drug Delivery System | Preparation Method | Characterization | Cell/Animal Model | Results | Ref. |
---|---|---|---|---|---|
Celastrol (6) MMP-9-responsive PLGA-RGD-PEG NPs (PRNPs) | 6-NPs (PLGA only) and 6-RNPs (PLGA + RGD) were prepared using the emulsion/solvent evaporation method. 6-PRNPs (PLGA + RGD + PEG) were obtained by linking 6-RNPs to the cleavable peptide PEG2000-MMP-9 using the water phase reaction method. | 6-NPs (PLGA only): size 155.7 ± 4.9 nm. 6-RNPs (PLGA + RGD): size 154.1 ± 4.6 nm, ZP −3.2 ± 0.6 mV. 6-PRNPs (PLGA + RGD + PEG): size 162.2 ± 6.6 nm, ZP −5.3 ± 0.4 mV. EE near 90% for all NPs. | LPS-activated murine BMDMs and osteoclasts. Human synovial macrophages and osteoclasts from late-stage RA patients. Male Wistar rats (n = 3) with early-stage or advanced adjuvant-induced arthritis (AA). |
| [72] |
Celastrol (6) Human serum albumin-Kolliphor®HS15 nanoparticles (HSA-HS15 NPs) | Addition of aqueous phase (12.5 mg Kolliphor® HS15 and 20% w/v HSA in 5 mL water) to organic phase (3.5 mg 6 and 22.5 mg soybean oil in 1 mL DCM) | 6-HSA-HS15 NPs: size 78.5 ± 2.7 nm, PDI 0.154 ± 0.02, ZP −1.45 ± 1.19 mV, DL 2.4 ± 0.97%, EE 94.6 ± 1.7%. 6-HSA NPs: size 74.9 ± 2.7 nm, PDI 0.164 ± 0.05, ZP −21.4 ± 1.34 mV, DL 2.6 ± 0.06%, EE 94.4 ± 2.3% | Adjuvant-induced arthritis (AA) in male SD rats (n = 7) |
| [73] |
Glycyrrhizin (7) in combination with budenoside Aminocellulose (AC)-grafted-polycaprolactone (PCL) coated gelatin NPs (PCL-AC-gel NPs) | 7-loaded gelatin NPs prepared by nanoprecipitation method and physically coated with budenoside-loaded PCL-AC layer. | 7-budenoside -loaded PCL-AC-gel NPs: size 210–225 nm, PDI 0.35, ZP 20.3 mV. Blank NPs: size 187.5 nm, PDI 0.25, ZP 11.2 mV. DL 13.85% (7) and 16.04% budenoside. EE 69.22% (7) and 80.20% budenoside | CIA in female Wistar rats (n = 6) |
| [74] |
11-keto-β-boswellic acid (8) PLGA NPs | 8-loaded PLGA NPs prepared by emulsion-diffusion-evaporation method with polymer/drug ratio of 50:10, PVA (1% w/v) as stabilizer and trehalose (10% w/v) as cryoprotectant. | Size 152.6 ± 4.4 nm; PDI 0.194 ± 0.085; ZP −3.18 ± 0.38 mV; EE 79.7 ± 1.99%. | Carrageenan-induced hind paw oedema in SD rats (n = 5). |
| [75] |
3-O-acetyl-11-keto-β-boswellic acid (9) PLGA NPs | 9-loaded PLGA NPs prepared by emulsion-diffusion-evaporation method with polymer/drug ratio of 50:10, PVA (1% w/v) as stabilizer and trehalose (10% w/v) as cryoprotectant. | Size 179.6 ± 7.51 nm; PDI 0.276 ± 0.057; EE 82.5 ± 1.55%. | Carrageenan-induced hind paw oedema in SD rats (n = 5). |
| [76] |
Ginsenoside Rb1 (10) Polymeric (PCL) nanocapsules (nanoGsRb1) | Polymeric nanocapsules made by mixing organic phase containing PCL (100 mg), sorbitan stearate (400 mg), propanone (25 mL) and 10 (80 mg) with aqueous phase containing glycol (75.9 mg in 49 mL water) | Size 173.1 ± 19.7 nm; ZP 36.9 mV; EE 99.79% | MSU-induced gouty arthritis in male SD rats (n = 8) |
| [77] |
Triterpenoid/ Drug Delivery System | Preparation Method | Characterization | Cell/Animal Model | Results | Ref. |
---|---|---|---|---|---|
Celastrol (6) Dextran sulphate-PVGIG-Celastrol (DPC) nanomicelles | Polymeric micelles (DPC) made by self-assembly of amphiphilic polymer comprising 6 as hydrophobic core and dextran sulfate (DS) as both hydrophilic block and SR-A ligand for targeting activated macrophages, linked by the MMP-2-responsive peptide PVGLIG. 6-loaded DPC micelles (DPC@6) prepared by the dialysis method. | DPC nanomicelles: CMC 0.1762 mg/mL. DPC@6 nanomicelles: size 189.9 nm, DPI 0.092, ZP −11.91 mV. DL 3.46% EE 38.07% | LPS-activated RAW264.7 cells and RA-FLSs. AA in SD rats (n = 5). |
| [78] |
Celastrol (6) ROS-responsive PEGylated bilirubin nanoparticles (BRNPs) | BRNPs prepared by self-assembly of amphiphilic polymer obtained by conjugating antioxidant and hydrophobic bilirubin (BR) with hydrophilic mPEG. 6-loaded BRNPs (6/BRNPs) prepared by self-assembly upon mixing PEGylated BR (25 mg/mL) with 6 (10 mg/mL) in DMSO/aqueous solution. | BRNPs: CMC 7 µg/mL. 6/BRNPs: size 68.6 nm, PDI 0.155) ZP −7.3 mV. DL 6.6% EE 72.6% | LPS-activated macrophages (RAW264.7 cells). AA in male SD rats (n = 5). |
| [79] |
Celastrol (6) Polymeric micelles | ROS-responsive PEG-b-PPS (PEPS) copolymer synthesized via multistep reaction. 6-loaded micelles (6-PEPS) prepared by self-assembly upon addition of 6 (5 mg) to PEPS (50 mg) in water | Mean size 135 nm, PDI 0.29, DL 4.71% | LPS-stimulated macrophages (RAW246.7 cells). CIA in male DBA/1 mice (n = 5–8). |
| [80] |
3-O-acetyl-11-keto-β-boswellic acid (9) Polymeric nanomicelles | Radical polymerization using N-isopropylacrylamide (NIPAAM), vinylpyrrolidone and acrylic acid at 65:30:5 molar ratio and methylene bis-acrylamide as cross-linker; transdermal gel of 9 (20 g)-loaded nanomicelles prepared using 1% w/v Carbopol 940. | Size 45 nm; DL 45%; EE 90% | Excised abdominal rat skin; carrageenan-induced hind paw oedema in Wistar rats (n = 5); AA in Wistar rats (n = 5). |
| [81] |
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Faustino, C.; Duarte, N.; Pinheiro, L. Triterpenes Drug Delivery Systems, a Modern Approach for Arthritis Targeted Therapy. Pharmaceuticals 2024, 17, 54. https://doi.org/10.3390/ph17010054
Faustino C, Duarte N, Pinheiro L. Triterpenes Drug Delivery Systems, a Modern Approach for Arthritis Targeted Therapy. Pharmaceuticals. 2024; 17(1):54. https://doi.org/10.3390/ph17010054
Chicago/Turabian StyleFaustino, Célia, Noélia Duarte, and Lídia Pinheiro. 2024. "Triterpenes Drug Delivery Systems, a Modern Approach for Arthritis Targeted Therapy" Pharmaceuticals 17, no. 1: 54. https://doi.org/10.3390/ph17010054
APA StyleFaustino, C., Duarte, N., & Pinheiro, L. (2024). Triterpenes Drug Delivery Systems, a Modern Approach for Arthritis Targeted Therapy. Pharmaceuticals, 17(1), 54. https://doi.org/10.3390/ph17010054