DEVELOPMENT AND OPTIMIZATION OF MESOPOROUS SILICA NANOPARTICLES LOADED WITH ADIANTUM PHILIPPINES FRACTION AND THUJA OIL AS A POTENTIAL WOUND HEALING AGENT
DOI:
https://doi.org/10.22159/ijap.2026v18i1.55787Keywords:
Mesoporous silica nanoparticles, Wound healing, Response surface methodology, Adiantum philippines, Thuja occidentalis, Controlled drug deliveryAbstract
Objective: This study aimed to develop and optimize mesoporous silica nanoparticles (MSNs) loaded with Adiantum Philippines chloroform fraction and Thuja occidentalis essential oil for enhanced wound healing applications, addressing the clinical need for improved topical therapeutic delivery systems.
Methods: MSNs were synthesized using the sol-gel method and optimized through box-behnken factorial design with three variables: CTAB concentration (1-3g), TEOS volume (8-16 ml), and stirring time (1-4h). Seventeen formulations were evaluated for particle size, zeta potential, and entrapment efficiency. The optimized formulation was characterized using FTIR, DSC, SEM, and DLS, followed by in vitro drug release and stability studies. Wound healing efficacy was assessed using full-thickness excision wounds in Balb-c mice over 14 d.
Results: The optimized F5 formulation, selected based on desirability function (1.000), demonstrated superior properties: particle size 89.3±4.8 nm, zeta potential-26.8±1.0mV, and entrapment efficiencies of 86.4% and 89.2% for AP and TO respectively. F5 exhibited controlled drug release (81-82% over 12h) and excellent stability over 6 mo. In vivo studies revealed significantly enhanced wound healing with 96.2±2.1% contraction at day 14 compared to control (72.3±4.8%) and standard treatment (89.1±3.5%) (p<0.01).
Conclusion: The optimized MSN formulation demonstrates promising wound healing potential with accelerated tissue regeneration compared to standard silver sulfadiazine treatment. These preclinical findings suggest potential for clinical development pending comprehensive safety, toxicity, and regulatory studies
References
1. Sen CK. Human wound and its burden: updated 2022 compendium of estimates. Adv Wound Care (New Rochelle). 2023;12(12):657-70. doi: 10.1089/wound.2023.0150, PMID 37756368.
2. Sen CK. Human wound and its burden: updated 2020 compendium of estimates. Adv Wound Care (New Rochelle). 2021;10(5):281-92. doi: 10.1089/wound.2021.0026, PMID 33733885.
3. Sharma A, Shankar R, Yadav AK, Pratap A, Ansari MA, Srivastava V. Burden of chronic nonhealing wounds: an overview of the worldwide humanistic and economic burden to the healthcare system. Int J Low Extrem Wounds. 2024;23(2):15347346241246339. doi: 10.1177/15347346241246339, PMID 38659348.
4. Mahendran MI, Gopalakrishnan V, Saravanan V, Dhamodharan R, Jothimani P, Balasubramanian M. Managing drug therapy-related problems and assessment of chronic diabetic wounds. Curr Med Res Opin. 2024;40(12):2077-93. doi: 10.1080/03007995.2024.2414893, PMID 39402701.
5. Sanjarnia P, Picchio ML, Polegre Solis AN, Schuhladen K, Fliss PM, Politakos N. Bringing innovative wound care polymer materials to the market: challenges, developments and new trends. Adv Drug Deliv Rev. 2024;207:115217. doi: 10.1016/j.addr.2024.115217, PMID 38423362.
6. Vidallon SL, Arriola AH. Checklist of ferns in Mt. Mariveles Bataan Philippines. Div Journ. 2024;9(4):e3134. doi: 10.48017/dj.v9i4.3134, PMID 39104572.
7. Galope Obemio CD, Buot IE JR, Banaticla Hilario MC. New records of pteridophytes in mount matutum protected landscape south central mindanao philippines with notes on its economic value and conservation status. J Threat Taxa. 2022;14(11):22039-57. doi: 10.11609/jott.7640.14.11.22039-22057, PMID 36421845.
8. De Villa K, Lagat R. Species richness, elevational distribution and conservation status of ferns and lycophytes in mts. palay-palay mataas-na-gulod protected landscape luzon Island, the philippines. Philipp J Sci. 2024;153(5):1887-33. doi: 10.56899/153.05.29.
9. Delos Angeles MD, Asis AA. Pteridophyte diversity in the Puerto Princesa Subterranean River National Park (PPSRNP), Palawan Island, Philippines. In: Ramamoorthy S, Buot IE Jr, Chandrasekaran R, editors. Plant genetic resources inventory collection and conservation. Singapore: Springer Nature; 2022. p. 177-87. doi: 10.1007/978-981-16-7699-4_8, PMID 35234156.
10. Sagar PK, Alam M, Sajwan S, Khan AS, Meena RP. HPTLC fingerprinting studies and evaluation of pharmacopoeial standards for the medicinal plant Adiantum capillus-veneris L. J Pharm Res Int. 2022;34(7):1-12. doi: 10.9734/jpri/2022/v34i730A35890, PMID 35789234.
11. Hooshmand S, Mollazadeh S, Akrami N, Ghanad M, El Fiqi A, Baino F. Mesoporous silica nanoparticles and mesoporous bioactive glasses for wound management: from skin regeneration to cancer therapy. Materials (Basel). 2021;14(12):3337. doi: 10.3390/ma14123337, PMID 34204198.
12. Heidari R, Assadollahi V, Shakib Manesh MH, Mirzaei SA, Elahian F. Recent advances in mesoporous silica nanoparticles formulations and drug delivery for wound healing. Int J Pharm. 2024;665:124654. doi: 10.1016/j.ijpharm.2024.124654, PMID 39244073.
13. Castillo RR, Vallet Regi M. Recent advances toward the use of mesoporous silica nanoparticles for the treatment of bacterial infections. Int J Nanomedicine. 2021;16:4409-30. doi: 10.2147/IJN.S273064, PMID 34234434.
14. Vallet Regi M, Schuth F, Lozano D, Colilla M, Manzano M. Engineering mesoporous silica nanoparticles for drug delivery: where are we after two decades? Chem Soc Rev. 2022;51(13):5365-451. doi: 10.1039/D1CS00659B, PMID 35642539.
15. Masood A, Maheen S, Khan HU, Shafqat SS, Irshad M, Aslam I. Pharmaco-technical evaluation of statistically formulated and optimized dual drug-loaded silica nanoparticles for improved antifungal efficacy and wound healing. ACS Omega. 2021;6(12):8210-25. doi: 10.1021/acsomega.0c06242, PMID 33817480.
16. Fung V, Xiao Y, Tan ZJ, Ma X, Zhou JF, Panda S. Producing aromatic amino acid from corn husk by using polyols as intermediates. Biomaterials. 2022;287:121661. doi: 10.1016/j.biomaterials.2022.121661, PMID 35842981.
17. Thakur M, Guleria P, Sobti RC, Gautam A, Kaur T. Comparative analysis of the antibacterial efficacy and bioactive components of Thuja occidentalis obtained from four different geographical sites. Mol Cell Biochem. 2024;479(2):283-96. doi: 10.1007/s11010-023-04729-9, PMID 37059893.
18. Thakur M, Sobti R, Kaur T. Medicinal and biological potential of Thuja occidentalis: a comprehensive review. Asian Pac J Trop Med. 2023;16(4):148-61. doi: 10.4103/1995-7645.374353, PMID 37162458.
19. Kwon S, Singh RK, Perez RA, Abou Neel EA, Kim HW, Chrzanowski W. Silica-based mesoporous nanoparticles for controlled drug delivery. J Tissue Eng. 2013;4:2041731413503357. doi: 10.1177/2041731413503357, PMID 24020012.
20. Mitchell MJ, Billingsley MM, Haley RM, Wechsler ME, Peppas NA, Langer R. Engineering precision nanoparticles for drug delivery. Nat Rev Drug Discov. 2021;20(2):101-24. doi: 10.1038/s41573-020-0090-8, PMID 33277608.
21. Rojek B, Wesolowski M. A combined differential scanning calorimetry and thermogravimetry approach for the effective assessment of drug substance-excipient compatibility. J Therm Anal Calorim. 2023;148(3):845-58. doi: 10.1007/s10973-022-11849-9, PMID 36531899.
22. Rojek B, Wesolowski M. DSC supported by factor analysis as a reliable tool for compatibility study in pharmaceutical mixtures. J Therm Anal Calorim. 2019;138(6):4531-9. doi: 10.1007/s10973-019-08223-7, PMID 31892976.
23. Vazquez NI, Gonzalez Z, Ferrari B, Castro Y. Synthesis of mesoporous silica nanoparticles by sol-gel as nanocontainer for future drug delivery applications. Bol Soc Espanola Ceram Vidrio. 2017;56(3):139-45. doi: 10.1016/j.bsecv.2017.03.002, PMID 28456321.
24. Qiao ZA, Zhang L, Guo M, Liu Y, Huo Q. Synthesis of mesoporous silica nanoparticles via controlled hydrolysis and condensation of silicon alkoxide. Chem Mater. 2009;21(16):3823-9. doi: 10.1021/cm901335k, PMID 19687234.
25. Rahmani S, Durand JO, Charnay C, Lichon L, Ferid M, Garcia M. Synthesis of mesoporous silica nanoparticles and nanorods: application to doxorubicin delivery. Solid State Sci. 2017;68:25-31. doi: 10.1016/j.solidstatesciences.2017.04.003, PMID 28453621.
26. Shahzad Y, Khalid SH. Formulation development and optimization of cefixime tablets by response surface methodology. Pak J Pharm Sci. 2019;32(4):1457-65. doi: 10.36721/PJPS.2019.32.4, PMID 31894089.
27. Zhu A, Jiao T, Ali S, Xu Y, Ouyang Q, Chen Q. SERS sensors based on aptamer-gated mesoporous silica nanoparticles for quantitative detection of Staphylococcus aureus with signal molecular release. Anal Chem. 2021;93(28):9788-96. doi: 10.1021/acs.analchem.1c01280, PMID 34236177.
28. Wagner J, Goßl D, Ustyanovska N, Xiong M, Hauser D, Zhuzhgova O. Mesoporous silica nanoparticles as pH-responsive carrier for the immune-activating drug resiquimod enhance the local immune response in mice. ACS Nano. 2021;15(3):4450-66. doi: 10.1021/acsnano.0c08384, PMID 33648336.
29. Singh AK, Singh SS, Rathore AS, Singh SP, Mishra G, Awasthi R. Lipid-coated MCM-41 mesoporous silica nanoparticles loaded with berberine improved inhibition of acetylcholine esterase and amyloid formation. ACS Biomater Sci Eng. 2021;7(8):3737-53. doi: 10.1021/acsbiomaterials.1c00514, PMID 34297529.
30. Paswan SK, Saini TR. Comparative evaluation of in vitro drug release methods employed for nanoparticle drug release studies. Diss Technol. 2021;28(4):30-8. doi: 10.14227/DT280421P30, PMID 34249158.
31. Barman P, Sharma C, Joshi S, Sharma S, Maan M, Rishi P. In vivo acute toxicity and therapeutic potential of a synthetic peptide, DP1 in a Staphylococcus aureus infected murine wound excision model. Probiotics Antimicrob Proteins. 2025;17(2):843-56. doi: 10.1007/s12602-023-10176-1, PMID 37910332.
32. Gushiken LF, Beserra FP, Hussni MF, Gonzaga MT, Ribeiro VP, De Souza PF. Beta-caryophyllene as an antioxidant anti-inflammatory and re-epithelialization activities in a rat skin wound excision model. Oxid Med Cell Longev. 2022;2022:9004014. doi: 10.1155/2022/9004014, PMID 35154574.
33. Gonzalez Gonzalez O, Ramirez IO, Ramirez BI, O Connell P, Ballesteros MP, Torrado JJ. Drug stability: ICH versus accelerated predictive stability studies. Pharmaceutics. 2022;14(11):2324. doi: 10.3390/pharmaceutics14112324, PMID 36365143.
34. Le Berre M, Gerlach JQ, Dziembala I, Kilcoyne M. Calculating half maximal inhibitory concentration (IC50) values from glycomics microarray data using GraphPad Prism. Methods Mol Biol. 2022;2460:89-111. doi: 10.1007/978-1-0716-2148-6_6, PMID 34972932.
35. Narayan R, Gadag S, Cheruku SP, Raichur AM, Day CM, Garg S. Chitosan-glucuronic acid conjugate coated mesoporous silica nanoparticles: a smart pH-responsive and receptor-targeted system for colorectal cancer therapy. Carbohydr Polym. 2021;261:117893. doi: 10.1016/j.carbpol.2021.117893, PMID 33766378.
36. Gou K, Wang Y, Guo X, Wang Y, Bian Y, Zhao H. Carboxyl-functionalized mesoporous silica nanoparticles for the controlled delivery of poorly water-soluble non-steroidal anti-inflammatory drugs. Acta Biomater. 2021;134:576-92. doi: 10.1016/j.actbio.2021.07.023, PMID 34280558.
37. Pham LM, Kim EC, Ou W, Phung CD, Nguyen TT, Pham TT. Targeting and clearance of senescent foamy macrophages and senescent endothelial cells by antibody-functionalized mesoporous silica nanoparticles for alleviating aorta atherosclerosis. Biomaterials. 2021;269:120677. doi: 10.1016/j.biomaterials.2021.120677, PMID 33503557.
38. Li H, Zhu J, Xu YW, Mou FF, Shan XL, Wang QL. Notoginsenoside R1-loaded mesoporous silica nanoparticles targeting the site of injury through inflammatory cells improves heart repair after myocardial infarction. Redox Biol. 2022;54:102384. doi: 10.1016/j.redox.2022.102384, PMID 35777198.
39. Yang Y, Chen F, Xu N, Yao Q, Wang R, Xie X. Red-light-triggered self-destructive mesoporous silica nanoparticles for cascade-amplifying chemo-photodynamic therapy favoring antitumor immune responses. Biomaterials. 2022;281:121368. doi: 10.1016/j.biomaterials.2022.121368, PMID 35030436.
40. Huang C, Zhang L, Guo Q, Zuo Y, Wang N, Wang H. Robust nanovaccine based on polydopamine-coated mesoporous silica nanoparticles for effective photothermal-immunotherapy against melanoma. Adv Funct Materials. 2021;31(18):2010637. doi: 10.1002/adfm.202010637, PMID 33854234.
41. Amin MU, Ali S, Ali MY, Tariq I, Nasrullah U, Pinnapreddy SR. Enhanced efficacy and drug delivery with lipid-coated mesoporous silica nanoparticles in cancer therapy. Eur J Pharm Biopharm. 2021;165:31-40. doi: 10.1016/j.ejpb.2021.04.020, PMID 33962002.
42. Zhang T, Liu H, Li L, Guo Z, Song J, Yang X. Leukocyte/platelet hybrid membrane-camouflaged dendritic large pore mesoporous silica nanoparticles co-loaded with photo/chemotherapeutic agents for triple negative breast cancer combination treatment. Bioact Mater. 2021;6(11):3865-78. doi: 10.1016/j.bioactmat.2021.04.004, PMID 33937590.
43. Zhang Y, Xiong M, Ni X, Wang J, Rong H, Su Y. Virus-mimicking mesoporous silica nanoparticles with an electrically neutral and hydrophilic surface to improve the oral absorption of insulin by breaking through dual barriers of the mucus layer and the intestinal epithelium. ACS Appl Mater Interfaces. 2021;13(15):18077-88. doi: 10.1021/acsami.1c00580, PMID 33830730.
44. Zhu M, Ou X, Tang J, Shi T, Ma X, Wang Y. Uptake distribution and translocation of Imidacloprid-loaded fluorescence double hollow shell mesoporous silica nanoparticles and metabolism of Imidacloprid in pakchoi. Sci Total Environ. 2021;787:147578. doi: 10.1016/j.scitotenv.2021.147578, PMID 33964772.
45. El Ashry RM, El Saadony MT, El Sobki AE, El Tahan AM, Al Otaibi S, El Shehawi AM. Biological silicon nanoparticles maximize the efficiency of nematicides against biotic stress induced by Meloidogyne incognita in eggplant. Saudi J Biol Sci. 2022;29(2):920-32. doi: 10.1016/j.sjbs.2021.10.013, PMID 35197760.
46. Mohamed Isa ED, Ahmad H, Abdul Rahman MB. Optimization of synthesis parameters of mesoporous silica nanoparticles based on ionic liquid by experimental design and its application as a drug delivery agent. J Nanomater. 2019;2019:1-8. doi: 10.1155/2019/4982054, PMID 31534567.
47. Juneja R, Vadarevu H, Halman J, Tarannum M, Rackley L, Dobbs J. Combination of nucleic acid and mesoporous silica nanoparticles: optimization and therapeutic performance in vitro. In: therapeutic RNA nanotechnology. Singapore: Jenny Stanford Publishing; 2021. p. 245-78. doi: 10.1201/9781003109198-10, PMID 34582145.
48. Saputra OA, Wibowo FR, Lestari WW. High storage capacity of curcumin loaded onto hollow mesoporous silica nanoparticles prepared via improved hard-templating method optimized by Taguchi DoE. Engineering Science and Technology an International Journal. 2022;33:101070. doi: 10.1016/j.jestch.2021.10.002, PMID 34891256.
49. Agi A, Junin R, Zaidi Jaafar M, Aishah Saidina Amin N, Akhmal Sidek M, Yakasai F. Process optimization of reservoir fines trapping by mesoporous silica nanoparticles using box-behnken design. Alex Eng J. 2022;61(11):8809-21. doi: 10.1016/j.aej.2022.02.016, PMID 35432987.
50. Arantes TM, Pinto AH, Leite ER, Longo E, Camargo ER. Synthesis and optimization of colloidal silica nanoparticles and their functionalization with methacrylic acid. Colloids Surf A Physicochem Eng Asp. 2012;415:209-17. doi: 10.1016/j.colsurfa.2012.09.041, PMID 23012456.
51. Khalbas AH, Albayati TM, Saady NM, Zendehboudi S, Salih IK, Tofah ML. Insights into drug loading techniques with mesoporous silica nanoparticles: optimization of operating conditions and assessment of drug stability. J Drug Deliv Sci Technol. 2024;96:105698. doi: 10.1016/j.jddst.2024.105698, PMID 38734521.
52. Mansor AF, Mohidem NA, Wan Mohd Zawawi WN, Othman NS, Endud S, Mat H. The optimization of synthesis conditions for laccase entrapment in mesoporous silica microparticles by response surface methodology. Micropor Mesopor Mater. 2016;220:308-14. doi: 10.1016/j.micromeso.2015.08.014, PMID 26432187.
53. Zhang Z, Mayoral A, Melian Cabrera I. Protocol optimization for the mild detemplation of mesoporous silica nanoparticles resulting in enhanced texture and colloidal stability. Micropor Mesopor Mater. 2016;220:110-9. doi: 10.1016/j.micromeso.2015.08.026, PMID 26531245.
54. Balis A, Zapotoczny S. Tailored synthesis of core-shell mesoporous silica particles optimization of dye sorption properties. Nanomaterials (Basel). 2018;8(4):230. doi: 10.3390/nano8040230, PMID 29642621.
55. Lestari WA, Saputra OA, Diaz Garcia D, Wahyuningsih S, Gomez Ruiz S, Wibowo FR. Design of experiments as a strategy for modulating the colloidal stability, physico-chemical properties and drug-delivery potential of small mesoporous silica nanoparticles. Adv Powder Technol. 2023;34(10):104191. doi: 10.1016/j.apt.2023.104191, PMID 37345678.
56. Kittappa S, Cui M, Ramalingam M, Ibrahim S, Khim J, Yoon Y. Synthesis mechanism and thermal optimization of an economical mesoporous material using silica: implications for the effective removal or delivery of ibuprofen. PLOS One. 2015;10(7):e0130253. doi: 10.1371/journal.pone.0130253, PMID 26161510.
Published
How to Cite
Issue
Section
Copyright (c) 2026 SWATI A. PAGAR, NILIMA A. THOMBRE
This work is licensed under a Creative Commons Attribution 4.0 International License.