DEVELOPMENT AND OPTIMIZATION OF MESOPOROUS SILICA NANOPARTICLE LOADED HYDROGEL OF ALLICIN FOR WOUND HEALING
DOI:
https://doi.org/10.22159/ijap.2025v17i6.55675Keywords:
Allicin, Mesoporous silica nanoparticles, MCM-41, Hydrogel, Wound healing, Factorial design, Ex-vivo permeation, Drug delivery optimizationAbstract
Objective: The objective of this study was to develop and optimize a mesoporous silica nanoparticle (MSN)-loaded hydrogel formulation of allicin to enhance its stability, sustained release, and skin permeation for effective wound healing.
Methods: Allicin was characterized through organoleptic, UV, solubility, FTIR, and DSC studies. MCM-41 MSNs were selected as carriers due to superior encapsulation efficiency and solubility enhancement. MSN-loaded hydrogels were formulated using a factorial design and evaluated for physicochemical properties, in vitro release, ex vivo permeation using Franz diffusion cells, and statistical optimization via ANOVA. Drug release kinetics were modeled using Zero-order, First-order, Higuchi, and Korsmeyer–Peppas equations. Accelerated stability studies were performed under ICH conditions for six months.
Results: Hydrogel formulations were stable, skin-compatible, and demonstrated uniform drug content (97.68–98.92%). In vitro release showed biphasic profiles with optimized formulations GF7 (94.26±4.18%) and GF5 (93.85±4.06%) achieving maximum release at 12 h. Ex vivo permeation confirmed superior performance of GF7 (95.42±3.65%) and GF5 (94.74±3.45%) with high flux (34.56 and 33.96 µg/cm²/h) and permeability coefficients (1.73×10⁻³ and 1.70×10⁻³ cm/h). ANOVA demonstrated significant influence of Carbopol and propylene glycol, and validation of optimized batch GF5 confirmed high model reliability (desirability 0.980). Release followed first-order kinetics (R² = 0.9789) with anomalous diffusion. Stability studies showed minimal changes in pH, viscosity, spreadability, drug content, and permeation over six months.
Conclusion: The MSN-based hydrogel system successfully enhanced allicin’s solubility, stability, sustained release, and skin permeation, offering a promising strategy for topical delivery of unstable phytoconstituents.
References
1. Sen CK. Human wound and its burden: updated 2020 compendium of estimates. Adv Wound Care (New Rochelle). 2021 May;10(5):281-92. doi: 10.1089/wound.2021.0026, PMID 33733885.
2. Sen CK. Human wound and its burden: updated 2022 compendium of estimates. Adv Wound Care (New Rochelle). 2023 Dec;12(12):657-70. doi: 10.1089/wound.2023.0150, PMID 37756368.
3. Graves N, Phillips CJ, Harding K. A narrative review of the epidemiology and economics of chronic wounds. Br J Dermatol. 2022;187(2):141-8. doi: 10.1111/bjd.20692, PMID 34549421.
4. Jodheea Jutton A, Hindocha S, Bhaw Luximon A. Health economics of diabetic foot ulcer and recent trends to accelerate treatment. Foot (Edinb). 2022;52:101909. doi: 10.1016/j.foot.2022.101909, PMID 36049265.
5. Bhatwalkar SB, Mondal R, Krishna SB, Adam JK, Govender P, Anupam R. Antibacterial properties of organosulfur compounds of garlic (Allium sativum). Front Microbiol. 2021 Jul 27;12:613077. doi: 10.3389/fmicb.2021.613077, PMID 34394014.
6. Yang X, Bai S, Wu J, Fan Y, Zou Y, Xia Z. Antifungal activity and potential action mechanism of allicin against trichosporon asahii. Microbiol Spectr. 2023;11(3):e0090723. doi: 10.1128/spectrum.00907-23, PMID 37199655.
7. Li Z, Li Z, Yang J, Lu C, Li Y, Luo Y. Allicin shows antifungal efficacy against Cryptococcus neoformans by blocking the fungal cell membrane. Front Microbiol. 2022 Oct 6;13:1012516. doi: 10.3389/fmicb.2022.1012516, PMID 36466672.
8. Schier C, Gruhlke MC, Reucher G, Slusarenko AJ, Rink L. Combating black fungus: using allicin as a potent antifungal agent against mucorales. Int J Mol Sci. 2023 Dec 15;24(24):17519. doi: 10.3390/ijms242417519, PMID 38139348.
9. Wang JR, Hu YM, Zhou H, Li AP, Zhang SY, Luo XF. Allicin-inspired heterocyclic disulfides as novel antimicrobial agents. J Agric Food Chem. 2022;70(37):11782-91. doi: 10.1021/acs.jafc.2c03765, PMID 36067412.
10. Xue L, Deng T, Guo R, Peng L, Guo J, Tang F. A composite hydrogel containing mesoporous silica nanoparticles loaded with artemisia argyi extract for improving chronic wound healing. Front Bioeng Biotechnol. 2022 Mar 21;10:825339. doi: 10.3389/fbioe.2022.825339, PMID 35402406.
11. Li Y, Chen X, Jin R, Chen L, Dang M, Cao H. Injectable hydrogel with MSNs/microRNA-21-5p delivery enables both immunomodification and enhanced angiogenesis for myocardial infarction therapy in pigs. Sci Adv. 2021;7(9):eabd6740. doi: 10.1126/sciadv.abd6740, PMID 33627421.
12. Stephen S, Gorain B, Choudhury H, Chatterjee B. Exploring the role of mesoporous silica nanoparticle in the development of novel drug delivery systems. Drug Deliv Transl Res. 2022 Jan;12(1):105-23. doi: 10.1007/s13346-021-00935-4, PMID 33604837.
13. Bosca B, Mot AC. Novel simultaneous determination of alliin and allicin in Allium sp. using digital subtraction HPTLC. J Chromatogr B Analyt Technol Biomed Life Sci. 2023;1222:123700. doi: 10.1016/j.jchromb.2023.123700, PMID 37031569.
14. Burhan GT, Ceylan C. Development of a new HPLC method for the identification of allicin and S-allyl cysteine in garlic (Allium sativum L.) extracts. Bezmialem Sci. 2023;11(1):69-76. doi: 10.14235/bas.galenos.2022.20591.
15. Nawaz A, Ullah S, Alnuwaiser MA, Rehman FU, Selim S, Al Jaouni SK. Formulation and evaluation of chitosan gelatin thermosensitive hydrogels containing 5fu-alginate nanoparticles for skin delivery. Gels. 2022 Sep 16;8(9):537. doi: 10.3390/gels8090537, PMID 36135249.
16. Nawaz A, Farid A, Safdar M, Latif MS, Ghazanfar S, Akhtar N. Formulation development and ex-vivo permeability of curcumin hydrogels under the influence of natural chemical enhancers. Gels. 2022 Jun 21;8(6):384. doi: 10.3390/gels8060384, PMID 35735728.
17. Kapare HS, Giram PS, Raut SS, Gaikwad HK, Paiva Santos AC. Formulation development and evaluation of Indian propolis hydrogel for wound healing. Gels. 2023 May 12;9(5):375. doi: 10.3390/gels9050375, PMID 37232965.
18. Chelu M, Popa M, Ozon EA, Pandele Cusu J, Anastasescu M, Surdu VA. High-content aloe vera-based hydrogels: physicochemical and pharmaceutical properties. Polymers (Basel). 2023 Mar 3;15(5):1312. doi: 10.3390/polym15051312, PMID 36904552.
19. Steinbach JC, Fait F, Mayer HA, Kandelbauer A. Sol-gel-controlled size and morphology of mesoporous silica microspheres using hard templates. ACS Omega. 2023 Aug 22;8(33):30273-84. doi: 10.1021/acsomega.3c03098, PMID 37636943.
20. Gao J, Ma S, Wang B, Ma Z, Guo Y, Cheng F. Template-free facile preparation of mesoporous silica from fly ash for shaped composite phase change materials. J Clean Prod. 2023 Feb 20;384:135583. doi: 10.1016/j.jclepro.2022.135583.
21. Budiman A, Aulifa DL. Encapsulation of drug into mesoporous silica by solvent evaporation: a comparative study of drug characterization in mesoporous silica with various molecular weights. Heliyon. 2021;7(12):e08627. doi: 10.1016/j.heliyon.2021.e08627, PMID 35005278.
22. Pouroutzidou GK, Liverani L, Theocharidou A, Tsamesidis I, Lazaridou M, Christodoulou E. Synthesis and characterization of mesoporous Mg- and Sr-doped nanoparticles for moxifloxacin drug delivery in promising tissue engineering applications. Int J Mol Sci. 2021 Jan 8;22(2):577. doi: 10.3390/ijms22020577, PMID 33430065.
23. Galabova BB. Mesoporous silica nanoparticles: synthesis, functionalization drug loading and release a review. Trop J Pharm Res. 2022;20(5):1091-100. doi: 10.4314/tjpr.v20i5.30.
24. Trzeciak K, Chotera Ouda A, Bak Sypien II, Potrzebowski MJ. Mesoporous silica particles as drug delivery systems the state of the art in loading methods and the recent progress in analytical techniques for monitoring these processes. Pharmaceutics. 2021 Jul 5;13(7):950. doi: 10.3390/pharmaceutics13070950, PMID 34202794.
25. Sivolapov P, Myronyuk O, Baklan D. Synthesis of Stober silica nanoparticles in solvent environments with different Hansen solubility parameters. Inorg Chem Commun. 2022 Sep;143:109769. doi: 10.1016/j.inoche.2022.109769.
26. Rapalli VK, Banerjee S, Khan S, Jha PN, Gupta G, Dua K. QbD-driven formulation development and evaluation of topical hydrogel containing ketoconazole-loaded cubosomes. Mater Sci Eng C Mater Biol Appl. 2021;119:111548. doi: 10.1016/j.msec.2020.111548, PMID 33321612.
27. Solanki D, Vinchhi P, Patel MM. Design considerations formulation approaches and strategic advances of hydrogel dressings for chronic wound management. ACS Omega. 2023 Mar 7;8(9):8172-89. doi: 10.1021/acsomega.2c06806, PMID 36910992.
28. De La Torre C, Coll C, Ultimo A, Sancenon F, Martinez Manez R, Ruiz Hernandez E. In situ-forming gels loaded with stimuli-responsive gated mesoporous silica nanoparticles for local sustained drug delivery. Pharmaceutics. 2023 Apr 5;15(4):1071. doi: 10.3390/pharmaceutics15041071, PMID 37111556.
29. Usgodaarachchi L, Thambiliyagodage C, Wijesekera R, Bakker MG. Synthesis of mesoporous silica nanoparticles derived from rice husk and surface-controlled amine functionalization for efficient adsorption of methylene blue from aqueous solution. Current Research in Green and Sustainable Chemistry. 2021;4:100116. doi: 10.1016/j.crgsc.2021.100116.
30. Rizzi F, Castaldo R, Latronico T, Lasala P, Gentile G, Lavorgna M. High surface area mesoporous silica nanoparticles with tunable size in the sub-micrometer regime: insights on the size and porosity control mechanisms. Molecules. 2021 Jul 13;26(14):4247. doi: 10.3390/molecules26144247, PMID 34299522.
31. Lyu X, Wu X, Liu Y, Huang W, Lee B, Li T. Synthesis and characterization of mesoporous silica nanoparticles loaded with Pt catalysts. Catalysts. 2022 Jan 31;12(2):183. doi: 10.3390/catal12020183, PMID 35626443.
32. Guo M, Han J, Ran Q, Zhao M, Liu Y, Zhu G. Multifunctional integrated electrochemical sensing platform based on mesoporous silica nanoparticles decorated single-wall carbon nanotubes network for sensitive determination of gallic acid. Ceram Int. 2023 Dec 1;49(23):37549-60. doi: 10.1016/j.ceramint.2023.09.081.
33. Guo L, Ping J, Qin J, Yang M, Wu X, You M. A comprehensive study of drug loading in hollow mesoporous silica nanoparticles: impacting factors and loading efficiency. Nanomaterials (Basel). 2021 May 14;11(5):1293. doi: 10.3390/nano11051293, PMID 34069019.
34. Haidari H, Kopecki Z, Sutton AT, Garg S, Cowin AJ, Vasilev K. pH-responsive “smart” hydrogel for controlled delivery of silver nanoparticles to infected wounds. Antibiotics (Basel). 2021 Jan 11;10(1):49. doi: 10.3390/antibiotics10010049, PMID 33466534.
35. Herrada Manchon H, Fernandez MA, Aguilar E. Essential guide to hydrogel rheology in extrusion 3D printing: how to measure it and why it matters? Gels. 2023 Jul 7;9(7):517. doi: 10.3390/gels9070517, PMID 37504396.
36. Alexander I, Krasnyuk II. Dermatologic gels spreadability measuring methods comparative study. Int J Appl Pharm. 2022;14(1):164-8. doi: 10.22159/ijap.2022v14i1.43133.
37. Alsareii SA, Ahmad J, Umar A, Ahmad MZ, Shaikh IA. Enhanced in vivo wound healing efficacy of a novel piperine-containing bioactive hydrogel in excision wound rat model. Molecules. 2023 Jan 16;28(2):545. doi: 10.3390/molecules28020545, PMID 36677613.
38. Kurniati M, Nuraini I, Winarti C. Investigation of swelling ratio and textures analysis of acrylamide nanocellulose corncobs hydrogel. J Phys.: Conf Ser. 2021;1805(1):012036. doi: 10.1088/1742-6596/1805/1/012036.
39. Zhang K, Feng Q, Fang Z, Gu L, Bian L. Structurally dynamic hydrogels for biomedical applications: pursuing a fine balance between macroscopic stability and microscopic dynamics. Chem Rev. 2021;121(18):11149-93. doi: 10.1021/acs.chemrev.1c00071, PMID 34189903.
40. Ahmad F, Mushtaq B, Ahmad S, Rasheed A, Nawab Y. A novel composite of hemp fiber and alginate hydrogel for wound dressings. J Polym Environ. 2023 Jun;31(6):2294-305. doi: 10.1007/s10924-023-02756-7.
41. Abadi B, Goshtasbi N, Bolourian S, Tahsili J, Adeli Sardou M, Forootanfar H. Electrospun hybrid nanofibers: fabrication, characterization and biomedical applications. Front Bioeng Biotechnol. 2022 Oct 11;10:986975. doi: 10.3389/fbioe.2022.986975, PMID 36561047.
42. Pargaonkar SS, Ghorpade VS, Mali KK, Dias RJ, Havaldar VD, Kadam VJ. Hydrogel films of citric acid cross-linked hydroxypropyl methylcellulose/methylcellulose for hydrophilic drug delivery. Ind J Pharm Edu Res. 2023;57(3):718-27. doi: 10.5530/ijper.57.3.87.
43. Dai JM, Zhang XQ, Zhang JJ, Yang WJ, Yang XM, Bian H. Blockade of mIL-6R alleviated lipopolysaccharide-induced systemic inflammatory response syndrome by suppressing NF-κB-mediated CCl2 expression and inflammasome activation. Med. 2022;3(2):e132. doi: 10.1002/mco2.132, PMID 35548710.
44. Xue Y, Yang F, Wu L, Xia D, Liu Y. CeO2 nanoparticles to promote wound healing: a systematic review. Adv Healthc Mater. 2024;13(6):e2302858. doi: 10.1002/adhm.202302858, PMID 37947125.
45. Pinheiro RG, Pinheiro M, Neves AR. Nanotechnology innovations to enhance the therapeutic efficacy of quercetin. Nanomaterials (Basel). 2021 Oct 12;11(10):2658. doi: 10.3390/nano11102658, PMID 34685098.
46. Alfei S, Schito GC, Schito AM, Zuccari G. Reactive oxygen species (ROS)-mediated antibacterial oxidative therapies: available methods to generate ROS and a novel option proposal. Int J Mol Sci. 2024 Jul 2;25(13):7182. doi: 10.3390/ijms25137182, PMID 39000290.
47. Yang S, Song Y, Dong H, Hu Y, Jiang J, Chang S. Stimuli-actuated turn on theranostic nanoplatforms for imaging-guided antibacterial treatment. Small. 2023 Dec;19(52):e2304127. doi: 10.1002/smll.202304127, PMID 37649207.
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