A Novel Strategy for Topical Administration by Combining Chitosan Hydrogel Beads with Nanostructured Lipid Carriers: Preparation, Characterization, and Evaluation
Abstract
:1. Introduction
2. Result and Discussion
2.1. Fabrication of Quercetin-Loaded NLC
2.2. Fabrication of NLC–Chitosan Hydrogel Beads
2.3. Influence of Chitosan Hydrogel Beads on NLC
2.3.1. Zeta Potential Analysis
2.3.2. Particle Size Analysis
2.4. Physical Characterizations of NLC–Chitosan Hydrogel Beads
2.4.1. Scanning Electron Microscopy (SEM) Analysis
2.4.2. Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR) Analysis
2.4.3. X-ray Diffraction (XRD) Analysis
2.4.4. Differential Scanning Calorimetry (DSC) Analysis
2.5. Chemical Stability Study
2.6. In Vitro Release Study
2.7. In Vitro Skin Permeation Study
2.8. Permeation Pathway Study Based on Hydrophobic Fluorescent Probe
3. Conclusions
4. Materials and Methods
4.1. Materials
4.2. Lipid Screening
4.3. Fabrication of NLC
4.4. Fabrication of NLC–Chitosan Hydrogel Beads
4.5. Encapsulation Efficiency
4.6. Particle Size and Zeta Potential Analysis
4.7. SEM Analysis
4.8. ATR-FTIR Analysis
4.9. XRD Analysis
4.10. DSC Analysis
4.11. Chemical Stability Study
4.12. In Vitro Release Study
4.13. In Vitro Skin Permeation Study
4.14. Permeation Pathway Study Based on Hydrophobic Fluorescent Probe
4.15. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Data Availability Statement
Conflicts of Interest
References
- Kulchar, R.J.; Singh, R.; Ding, S.; Alexander, E.; Daniell, H.; Leong, K.W. Delivery of biologics: Topical administration. Biomaterials 2023, 302, 122312. [Google Scholar] [CrossRef]
- Md, S.; Haque, S.; Madheswaran, T.; Zeeshan, F.; Mekal, V.S.; Radhakrishnan, A.K.; Kesharwani, P. Lipid based nanocarriers system for topical delivery of photosensitizers. Drug Discov. Today 2017, 22, 1274–1283. [Google Scholar] [CrossRef] [PubMed]
- Costa, R.; Santos, L. Delivery systems for cosmetics—From manufacturing to the skin of natural antioxidants. Powder Technol. 2017, 322, 402–416. [Google Scholar] [CrossRef]
- Müller, R.H.; Radtke, M.; Wissing, S.A. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) in cosmetic and dermatological preparations. Adv. Drug Deliv. Rev. 2002, 54, S131–S155. [Google Scholar] [CrossRef] [PubMed]
- Mehnert, W.; Maeder, K. Solid lipid nanoparticles Production, characterization and applications. Adv. Drug Deliv. Rev. 2012, 64, 83–101. [Google Scholar] [CrossRef]
- Garces, A.; Amaral, M.H.; Sousa Lobo, J.M.; Silva, A.C. Formulations based on solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) for cutaneous use: A review. Eur. J. Pharm. Sci. 2018, 112, 159–167. [Google Scholar] [CrossRef] [PubMed]
- Muller, R.H.; Shegokar, R.; Keck, C.M. 20 years of lipid nanoparticles (SLN and NLC): Present state of development and industrial applications. Curr. Drug Discov. Technol. 2011, 8, 207–227. [Google Scholar] [CrossRef] [PubMed]
- Abedi, E.; Akhavan, H.-R.; Mohammadi, H.; Banasaz, S. Structure-based modifications of nano lipid carriers: Comparative review on release properties and anti-microbial activities of bioactive compounds. Food Control 2024, 159, 110237. [Google Scholar] [CrossRef]
- Mou, D.; Chen, H.; Du, D.; Mao, C.; Wan, H.; Xu, H.; Yang, X. Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs. Int. J. Pharm. 2008, 353, 270–276. [Google Scholar] [CrossRef]
- Doktorovova, S.; Souto, E.B. Nanostructured lipid carrier-based hydrogel formulations for drug delivery: A comprehensive review. Expert Opin. Drug Deliv. 2009, 6, 165–176. [Google Scholar] [CrossRef]
- Liu, M.; Liu, D.; Cheng, Y.; Mei, Q.; Zhou, S. A resveratrol-loaded nanostructured lipid carrier hydrogel to enhance the anti-UV irradiation and anti-oxidant efficacy. Colloids Surf. B-Biointerfaces 2021, 204, 111786. [Google Scholar]
- Czajkowska-Kosnik, A.; Szymanska, E.; Winnicka, K. Nanostructured Lipid Carriers (NLC)-Based Gel Formulations as Etodolac Delivery: From Gel Preparation to Permeation Study. Molecules 2023, 28, 235. [Google Scholar] [CrossRef] [PubMed]
- Lima Nascimento, L.G.; Casanova, F.; Nogueira Silva, N.F.; de Carvalho Teixeira, A.V.N.; de Carvalho, A.F. Casein-based hydrogels: A mini-review. Food Chem. 2020, 314, 126063. [Google Scholar] [CrossRef] [PubMed]
- Su, J.J.; Li, J.K.; Liang, J.H.; Zhang, K.; Li, J.A. Hydrogel Preparation Methods and Biomaterials for Wound Dressing. Life 2021, 11, 1016. [Google Scholar] [CrossRef] [PubMed]
- Hashemi, B.; Assadpour, E.; Zhang, F.; Jafari, S.M. A comparative study of the impacts of preparation techniques on the rheological and textural characteristics of emulsion gels (emulgels). Adv. Colloid Interface Sci. 2023, 322, 103051. [Google Scholar] [CrossRef] [PubMed]
- Farjami, T.; Madadlou, A. An overview on preparation of emulsion-filled gels and emulsion particulate gels. Trends Food Sci. Technol. 2019, 86, 85–94. [Google Scholar] [CrossRef]
- Xiao, J.; Shi, C.; Li, Y.; Pan, Y.; Huang, Q. Pickering emulsions immobilized within hydrogel matrix with enhanced resistance against harsh processing conditions and sequential digestion. Food Hydrocoll. 2017, 62, 35–42. [Google Scholar] [CrossRef]
- Cascone, S.; Lamberti, G. Hydrogel-based commercial products for biomedical applications: A review. Int. J. Pharm. 2020, 573, 118803. [Google Scholar] [CrossRef] [PubMed]
- Patel, H.K.; Barot, B.S.; Parejiya, P.B.; Shelat, P.K.; Shukla, A. Topical delivery of clobetasol propionate loaded microemulsion based gel for effective treatment of vitiligo: Ex vivo permeation and skin irritation studies. Colloids Surf. B-Biointerfaces 2013, 102, 86–94. [Google Scholar] [CrossRef]
- Shahid, M.; Alrumayyan, B.F.; Ramzan, M.; Ahmed, F.J.; Malik, A.; Khuroo, T.; Alaofi, A.L. Impact of miconazole nitrate ferrying cationic and anionic nanoemulsion and gels on permeation profiles of across EpiDerm, artificial membrane, and skin: Instrumental evidences. Int. J. Pharm. 2023, 648, 123593. [Google Scholar] [CrossRef]
- Li, L.; He, M.; Fang, C.; Zhang, Y.; Wang, Y.; Song, X.; Zou, Y.; Jia, R.; Liang, X.; Yin, L.; et al. Preparation, characterization, ex vivo transdermal properties and skin irritation evaluation of 1,8-cineole nanoemulsion gel. Int. J. Pharm. 2022, 624, 121982. [Google Scholar] [CrossRef]
- Hamedi, H.; Moradi, S.; Hudson, S.M.; Tonelli, A.E. Chitosan based hydrogels and their applications for drug delivery in wound dressings: A review. Carbohydr. Polym. 2018, 199, 445–460. [Google Scholar] [CrossRef]
- Lee, E.-H.; Lim, S.-J.; Lee, M.-K. Chitosan-coated liposomes to stabilize and enhance transdermal delivery of indocyanine green for photodynamic therapy of melanoma. Carbohydr. Polym. 2019, 224, 115143. [Google Scholar] [CrossRef] [PubMed]
- Nan, W.; Ding, L.; Chen, H.; Khan, F.U.; Yu, L.; Sui, X.; Shi, X. Topical Use of Quercetin-Loaded Chitosan Nanoparticles Against Ultraviolet B Radiation. Front. Pharmacol. 2018, 9, 826. [Google Scholar] [CrossRef] [PubMed]
- Cordenonsi, L.M.; Faccendini, A.; Catanzaro, M.; Bonferoni, M.C.; Rossi, S.; Malavasi, L.; Raffin, R.P.; Scherman Schapoval, E.E.; Lanni, C.; Sandri, G.; et al. The role of chitosan as coating material for nanostructured lipid carriers for skin delivery of fucoxanthin. Int. J. Pharm. 2019, 567, 118487. [Google Scholar] [CrossRef] [PubMed]
- Petroni, S.; Tagliaro, I.; Antonini, C.; D’Arienzo, M.; Orsini, S.F.; Mano, J.F.; Brancato, V.; Borges, J.; Cipolla, L. Chitosan-Based Biomaterials: Insights into Chemistry, Properties, Devices, and Their Biomedical Applications. Mar. Drugs 2023, 21, 147. [Google Scholar] [CrossRef] [PubMed]
- Liu, L.; Gao, Q.; Lu, X.; Zhou, H. In situ forming hydrogels based on chitosan for drug delivery and tissue regeneration. Asian J. Pharm. Sci. 2016, 11, 673–683. [Google Scholar] [CrossRef]
- de Moura, M.R.; Aouada, F.A.; Avena-Bustillos, R.J.; McHugh, T.H.; Krochta, J.M.; Mattoso, L.H.C. Improved barrier and mechanical properties of novel hydroxypropyl methylcellulose edible films with chitosan/tripolyphosphate nanoparticles. J. Food Eng. 2009, 92, 448–453. [Google Scholar] [CrossRef]
- Batiha, G.E.-S.; Beshbishy, A.M.; Ikram, M.; Mulla, Z.S.; Abd El-Hack, M.E.; Taha, A.E.; Algammal, A.M.; Elewa, Y.H.A. The Pharmacological Activity, Biochemical Properties, and Pharmacokinetics of the Major Natural Polyphenolic Flavonoid: Quercetin. Foods 2020, 9, 374. [Google Scholar] [CrossRef]
- Imran, M.; Iqubal, M.K.; Imtiyaz, K.; Saleem, S.; Mittal, S.; Rizvi, M.M.A.; Ali, J.; Baboota, S. Topical nanostructured lipid carrier gel of quercetin and resveratrol: Formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer. Int. J. Pharm. 2020, 587, 119705. [Google Scholar] [CrossRef]
- Teeranachaideekul, V.; Boonme, P.; Souto, E.B.; Mueller, R.H.; Junyaprasert, V.B. Influence of oil content on physicochemical properties and skin distribution of Nile red-loaded NLC. J. Control. Release 2008, 128, 134–141. [Google Scholar] [CrossRef]
- Nanjwade, B.K.; Kadam, V.T.; Manvi, F.V. Formulation and Characterization of Nanostructured Lipid Carrier of Ubiquinone (Coenzyme Q10). J. Biomed. Nanotechnol. 2013, 9, 450–460. [Google Scholar] [CrossRef]
- Lee, S.A.; Joung, H.J.; Park, H.J.; Shin, G.H. Preparation of Chitosan-Coated Nanostructured Lipid Carriers (CH-NLCs) to Control Iron Delivery and Their Potential Application to Food Beverage System. J. Food Sci. 2017, 82, 904–912. [Google Scholar] [CrossRef]
- Tai, K.; Rappolt, M.; Mao, L.; Gao, Y.; Li, X.; Yuan, F. The stabilization and release performances of curcumin-loaded liposomes coated by high and low molecular weight chitosan. Food Hydrocoll. 2020, 99, 105355. [Google Scholar] [CrossRef]
- Guzey, D.; McClements, D.J. Formation, stability and properties of multilayer emulsions for application in the food industry. Adv. Colloid Interface Sci. 2006, 128, 227–248. [Google Scholar] [CrossRef] [PubMed]
- Schönhoff, M. Layered polyelectrolyte complexes: Physics of formation and molecular properties. J. Phys.-Condens. Matter 2003, 15, R1781–R1808. [Google Scholar] [CrossRef]
- Wang, M.; Zhao, T.; Liu, Y.; Wang, Q.; Xing, S.; Li, L.; Wang, L.; Liu, L.; Gao, D. Ursolic acid liposomes with chitosan modification: Promising antitumor drug delivery and efficacy. Mater. Sci. Eng. C-Mater. Biol. Appl. 2017, 71, 1231–1240. [Google Scholar] [CrossRef] [PubMed]
- Huang, J.; Wang, Q.; Li, T.; Xia, N.; Xia, Q. Multilayer emulsions as a strategy for linseed oil and α-lipoic acid micro-encapsulation: Study on preparation and in vitro characterization. J. Sci. Food Agric. 2018, 98, 3513–3523. [Google Scholar] [CrossRef] [PubMed]
- Bunjes, H.; Unruh, T. Characterization of lipid nanoparticles by differential scanning calorimetry, X-ray and neutron scattering. Adv. Drug Deliv. Rev. 2007, 59, 379–402. [Google Scholar] [CrossRef] [PubMed]
- Sandri, G.; Motta, S.; Bonferoni, M.C.; Brocca, P.; Rossi, S.; Ferrari, F.; Rondelli, V.; Cantu, L.; Caramella, C.; Del Favero, E. Chitosan-coupled solid lipid nanoparticles: Tuning nanostructure and mucoadhesion. Eur. J. Pharm. Biopharm. 2017, 110, 13–18. [Google Scholar] [CrossRef] [PubMed]
- Muller, R.H.; Radtke, M.; Wissing, S.A. Nanostructured lipid matrices for improved microencapsulation of drugs. Int. J. Pharm. 2002, 242, 121–128. [Google Scholar] [CrossRef]
- Spireas, S.; Sadu, S. Enhancement of prednisolone dissolution properties using liquisolid compacts. Int. J. Pharm. 1998, 166, 177–188. [Google Scholar] [CrossRef]
- Karadzovska, D.; Brooks, J.D.; Monteiro-Riviere, N.A.; Riviere, J.E. Predicting skin permeability from complex vehicles. Adv. Drug Deliv. Rev. 2013, 65, 265–277. [Google Scholar] [CrossRef] [PubMed]
- Xu, H.-L.; Chen, P.-P.; Wang, L.-f.; Xue, W.; Fu, T.-L. Hair regenerative effect of silk fibroin hydrogel with incorporation of FGF-2-liposome and its potential mechanism in mice with testosterone-induced alopecia areata. J. Drug Deliv. Sci. Technol. 2018, 48, 128–136. [Google Scholar] [CrossRef]
- Sachdeva, B.; Sachdeva, P.; Negi, A.; Ghosh, S.; Han, S.; Dewanjee, S.; Jha, S.K.; Bhaskar, R.; Sinha, J.K.; Paiva-Santos, A.C.; et al. Chitosan Nanoparticles-Based Cancer Drug Delivery: Application and Challenges. Mar. Drugs 2023, 21, 211. [Google Scholar] [CrossRef] [PubMed]
- Kahraman, E.; Ozhan, G.; Ozsoy, Y.; Gungor, S. Polymeric micellar nanocarriers of benzoyl peroxide as potential follicular targeting approach for acne treatment. Colloids Surf. B-Biointerfaces 2016, 146, 692–699. [Google Scholar] [CrossRef]
- Corrias, F.; Schlich, M.; Sinico, C.; Pireddu, R.; Valenti, D.; Fadda, A.M.; Marceddu, S.; Lai, F. Nile red nanosuspensions as investigative model to study the follicular targeting of drug nanocrystals. Int. J. Pharm. 2017, 524, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Kurtz, S.L.; Lawson, L.B. Determination of permeation pathways of hydrophilic or hydrophobic dyes through the mammary papilla. Int. J. Pharm. 2018, 545, 10–18. [Google Scholar] [CrossRef]
- Mendes, M.; Nunes, S.C.C.; Sousa, J.J.; Pais, A.A.C.C.; Vitorino, C. Expanding Transdermal Delivery with Lipid Nanoparticles: A New Drug-in-NLC-in-Adhesive Design. Mol. Pharm. 2017, 14, 2099–2115. [Google Scholar] [CrossRef]
- Vidlarova, L.; Hanus, J.; Vesely, M.; Ulbrich, P.; Stepanek, F.; Zbytovska, J. Effect of lipid nanoparticle formulations on skin delivery of a lipophilic substance. Eur. J. Pharm. Biopharm. 2016, 108, 289–296. [Google Scholar] [CrossRef]
- Krishnan, V.; Mitragotri, S. Nanoparticles for topical drug delivery: Potential for skin cancer treatment. Adv. Drug Deliv. Rev. 2020, 153, 87–108. [Google Scholar] [CrossRef]
- Scheuplein, R.J. Mechanism of percutaneous absorption. II. Transient diffusion and the relative importance of various routes of skin penetration. J. Investig. Dermatol. 1967, 48, 79–88. [Google Scholar] [CrossRef]
- Luedtke, F.L.; Stahl, M.A.; Grimaldi, R.; Forte, M.B.S.; Gigante, M.L.; Ribeiro, A.P.B. Optimization of high pressure homogenization conditions to produce nanostructured lipid carriers using natural and synthetic emulsifiers. Food Res. Int. 2022, 160, 111746. [Google Scholar] [CrossRef]
- Yuan, D.; Jacquier, J.C.; O’Riordan, E.D. Entrapment of protein in chitosan-tripolyphosphate beads and its release in an in vitro digestive model. Food Chem. 2017, 229, 495–501. [Google Scholar] [CrossRef]
- Marathe, S.; Shadambikar, G.; Mehraj, T.; Sulochana, S.P.; Dudhipala, N.; Majumdar, S. Development of α-Tocopherol Succinate-Based Nanostructured Lipid Carriers for Delivery of Paclitaxel. Pharmaceutics 2022, 14, 1034. [Google Scholar] [CrossRef]
- Malekmohammadi, M.; Ghanbarzadeh, B.; Hanifian, S.; Kafil, H.S.; Gharekhani, M.; Falcone, P.M. The Gelatin-Coated Nanostructured Lipid Carrier (NLC) Containing Salvia officinalis Extract: Optimization by Combined D-Optimal Design and Its Application to Improve the Quality Parameters of Beef Burger. Foods 2023, 12, 3737. [Google Scholar] [CrossRef]
- Alam, M.; Rizwanullah, M.; Mir, S.R.; Amin, S. Statistically Optimized Tacrolimus and Thymoquinone Co-Loaded Nanostructured Lipid Carriers Gel for Improved Topical Treatment of Psoriasis. Gels 2023, 9, 515. [Google Scholar] [CrossRef] [PubMed]
- Eid, R.K.; Ashour, D.S.; Essa, E.A.; El Maghraby, G.M.; Arafa, M.F. Chitosan coated nanostructured lipid carriers for enhanced in vivo efficacy of albendazole against Trichinella spiralis. Carbohydr. Polym. 2020, 232, 115826. [Google Scholar] [CrossRef] [PubMed]
- Thien Hoang, T.; Alcantara, K.P.; Bulatao, B.P.I.; Sorasitthiyanukarn, F.N.; Muangnoi, C.; Nalinratana, N.; Vajragupta, O.; Rojsitthisak, P.; Rojsitthisak, P. Chitosan-coated nanostructured lipid carriers for transdermal delivery of tetrahydrocurcumin for breast cancer therapy. Carbohydr. Polym. 2022, 288, 119401. [Google Scholar]
- Bose, S.; Du, Y.; Takhistov, P.; Michniak-Kohn, B. Formulation optimization and topical delivery of quercetin from solid lipid based nanosystems. Int. J. Pharm. 2013, 441, 56–66. [Google Scholar] [CrossRef] [PubMed]
- Kumar, M.; Sharma, A.; Mahmood, S.; Thakur, A.; Mirza, M.A.; Bhatia, A. Franz diffusion cell and its implication in skin permeation studies. J. Dispers. Sci. Technol. 2023, 1–14. [Google Scholar] [CrossRef]
- Ning, X.; Wiraja, C.; Lio, D.C.S.; Xu, C. A Double-Layered Microneedle Platform Fabricated through Frozen Spray-Coating. Adv. Healthc. Mater. 2020, 9, e2000147. [Google Scholar] [CrossRef] [PubMed]
Liquid Lipids | Solubility of Quercetin (mg/g) |
---|---|
Peanut oil | 2.1 |
Octyl decyl glycerate | 5.2 |
Grape seed oil | 2.3 |
Tea seed oil | 1.9 |
Corn oil | 2.4 |
Evening primrose oil | 1.8 |
Olive oil | 2.2 |
Solid Lipids | Solubility of Quercetin (mg/g) | Compatibility |
---|---|---|
Stearic acid | 11.3 | − |
Propylene glycol monostearate | 4.4 | − |
Glycerol monostearate | 10.4 | + |
Mean Particle Size (nm) | PDI | Zeta Potential (mV) | |
---|---|---|---|
NLC (with quercetin) | 77.8 ± 2.7 | 0.168 ± 0.017 | −35.6 ± 1.9 |
Empty NLC | 74.4 ± 1.1 | 0.209 ± 0.009 | −41.2 ± 1.3 |
NLC | NLC–Chitosan Hydrogel Beads | |
---|---|---|
3 h | 4.154 | 4.088 |
6 h | 3.910 | 5.198 |
9 h | 6.842 | 9.867 |
12 h | 12.048 | 15.040 |
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Sun, R.; Xia, Q.; Sun, Y. A Novel Strategy for Topical Administration by Combining Chitosan Hydrogel Beads with Nanostructured Lipid Carriers: Preparation, Characterization, and Evaluation. Gels 2024, 10, 160. https://doi.org/10.3390/gels10030160
Sun R, Xia Q, Sun Y. A Novel Strategy for Topical Administration by Combining Chitosan Hydrogel Beads with Nanostructured Lipid Carriers: Preparation, Characterization, and Evaluation. Gels. 2024; 10(3):160. https://doi.org/10.3390/gels10030160
Chicago/Turabian StyleSun, Rui, Qiang Xia, and Yufeng Sun. 2024. "A Novel Strategy for Topical Administration by Combining Chitosan Hydrogel Beads with Nanostructured Lipid Carriers: Preparation, Characterization, and Evaluation" Gels 10, no. 3: 160. https://doi.org/10.3390/gels10030160