Hydrogels containing spray-dried avobenzone and resveratrol-loaded nanocapsules using titanium dioxide and microalgae as drying adjuvants: An innovative formulation for photoprotection

Authors

DOI:

https://doi.org/10.22456/2527-2616.147538

Keywords:

Avobenzone, Hydrogel, Microalgae, Microparticles, Photoprotectors, HPLC

Abstract

Photoprotective substances are needed to minimize the harmful effects of UV radiation on the skin. In this context, the objective of this work was to develop and characterize a hydrogel containing spray-dried avobenzone and resveratrol loaded nanocapsules using titanium dioxide and microalgae as drying adjuvants. The nanocapsules, previously developed and characterized, were dried using the spray drying technique with the aid of titanium dioxide (3% w/v) and/or a mixture of it (2.7% w/v) with the microalgae of the species Scenedesmus ecornis as excipients (0.3% w/v). The powders showed good yields (67-70%), with low moisture content (<1.5%) and average particle size in the micrometer range (>30 µm). The drying process of spray-dried powders did not significantly affect the content of avobenzone and resveratrol (above 85% for both), although the morphological description indicates the presence of micro-agglomerates. Subsequently, the powders were incorporated into hydrophilic gels prepared with sodium acrylates copolymer and lecithin. Then, the hydrogel containing spray-dried avobenzone and resveratrol loaded nanocapsules was produced and characterized using titanium dioxide and microalgae (HG-NCA+R+TiM) as a drying adjuvant. The formulation was evaluated for irritability by HET-CAM, permeation/penetration of avobenzone, washability profile and in vitro efficacy. The hydrogel presented a pH value of 7.52, drug content of 1.24% for avobenzone (w/w) and 0.04% for resveratrol (w/w), and a non-Newtonian pseudoplastic rheological behavior. The free avobenzone from a hydrogel and from HG-NCA+R+TiM did not permeate the skin layers. The evaluation by HET-CAM did not detect irritating reactions of the formulation. The structure of HG-NCA+R+TiM allowed a greater resistance to the washing flow indicating good adhesive capacity on the skin surface in comparison to the free hydrogel. The in vitro efficacy test showed that HG-NCA+R+TiM absorbed and spreaded the UV light with maximum wavelengths in the erythematous range (305-328 nm). In conclusion, these spray-dried powders are promising formulations to be incorporated into photoprotective hydrogels intended for cutaneous administration.

 

Downloads

Download data is not yet available.

References

Kim, J. C., Park, T. J., & Kang, H. Y. Skin-aging pigmentation: who is the real enemy? Cells. (2022), 11(16), 2541.

Salminen, A., Kaarniranta, K., & Kauppinen, A. Photoaging: UV radiation-induced inflammation and immunosuppression accelerate the aging process in the skin. Inflammation Research, (2022), 71(7-8), 817-831.

Wei, M., He, X., Liu, N., & Deng, H. Role of reactive oxygen species in ultraviolet-induced photodamage of the skin. Cell division, (2024), 19(1), 1.

S. S. Guterres, K. Paese, A. R. Pohlmann. Polymeric Nanoparticles. In: Nanocosmetics. Springer, Cham. (2019), pp. 73-94.

S. Tampucci, S. Burgalassi, P. Chetoni, D. Monti. Cutaneous permeation and penetration of sunscreens: formulation strategies and in vitro methods. Cosmetics., 5 (2018), pp. 1-14.

J. A. Berenbeim, N. G. Wong, M. C. Cockett, G. Berden, J. Oomens, A. M. Rijs, C. E. Dessent. Unravelling the Keto-Enol Tautomer Dependent Photochemistry and Degradation Pathways of the Protonated UVA Filter Avobenzone. J Phys Chem A., 124 (2020), pp. 2919-2930.

Sharma, A., Kuhad, A., & Bhandari, R. Novel nanotechnological approaches for treatment of skin-aging. Journal of tissue viability, (2022), 31(3), 374-386.

B. Tian, J. Liu. Resveratrol: a review of plant sources, synthesis, stability, modification, and food application. J Sci Food Agric., 100 (2020), pp. 1392-1404.

C. Detoni, G. D. Souto, A. L. M. Da Silva, A. R. Pohlmann, S. S. Guterres. Photostability and Skin Penetration of Different E‐Resveratrol‐Loaded Supramolecular Structures. Photochem Photobiol., 88 (2012), pp. 913-921.

K. Coradini, F. O. Lima, C. M. Oliveira, P. S. Chaves, M. L. Athayde, L. M. Carvalho, R. C. R. Beck. Co-encapsulation of resveratrol and curcumin in lipid-core nanocapsules improves their in vitro antioxidant effects. Eur J Pharm Biopharm., 88 (2014), pp. 178-185.

S. Davies, R. V. Contri, S. S. Guterres, A. R. Pohlmann, I. C. Külkamp. Simultaneous nanoencapsulation of lipoic acid and resveratrol with improved antioxidant properties for the skin. Colloids Surf B: Biointerfaces., 192 (2020), 111023 pp. 1-10.

S. S. Guterres, R. C. R. Beck, A. R. Pohlmann. Spray-drying technique to prepare innovative nanoparticulate formulations for drug administration: a brief overview. Braz J Phys., 39 (2009), pp. 205-209.

R. Vehring, H. Snyder, D. Lechuga‐Ballesteros. Spray Drying. In: Drying Technologies for Biotechnology and Pharmaceutical Applications., (2020) pp. 179-216.

R. Sarrate, J. R. Ticó, M. Miñarro, C. Carrillo, A. Fàbregas, E. García-Montoya, P. Pérez-Lozano, J. M. Suñé-Negre. Modification of the morphology and particle size of pharmaceutical excipients by spray drying technique. Powder Technol., 270 (2015), pp. 244-255.

C. R. Müller, V. L. Bassani, A. R. Pohlmann, C. B. Michalowski, P. R. Petrovich, S. S. Guterres. Preparation and Characterization of Spray-Dried Polymeric Nanocapsules. Drug Dev Ind Pharm., 26 (2000), pp. 343–347.

D. Tang, W. Han, P. Li, X. Miao, J. Zhong. CO2 biofixation and fatty acid composition of Scenedesmus obliquus and Chlorella pyrenoidosa in response to different CO2 levels. Bioresource Technol., 102 (2011), pp. 3071-3076.

H. Ren, B. Liu, C. Ma, L. Zhao, N. Ren. A new lipid-rich microalga Scenedesmus sp. strain R-16 isolated using Nile red staining: effects of carbon and nitrogen sources and initial pH on the biomass and lipid production. Biotechnol Biofuels., 6 (2013), pp. 1-10.

G. F. Almeida, P. H. De Araújo, A. C. Florentino, R. M. Bezerra, J. C. Carvalho, S. M. Faustino, I. M. Ferreira. Fatty acid ethyl esters from microalgae of Scenedesmus ecornis by enzymatic and acid catalysis. Quim Nova., 41 (2018), pp. 1-4.

M. B. Ariede, T. M. Candido, A. L. M. Jacome, M. V. R. Velasco, J. C. M. Carvalho, A. R. Baby. Cosmetic attributes of algae-A review. Algal Res., 25 (2017), pp. 483-487.

C. E. M. Bicudo, M. Menezes. Gêneros de algas de águas continentais do Brasil: chave para identificação e descrições. 2 ed. São Carlos: RiMa, 2006. 502p.

C. G. Venturini; E. Jäger, C. P. Oliveira, A. Bernardi, A. M. Battastini, S. S. Guterres, A. R. Pohlmann. Formulation of lipid core nanocapsules. Colloids Surf A., 375 (2011), pp. 200-208.

C. Puglia, E. Damiani, A. Offerta, L. Rizza, G. G. Tirendi, M. S. Tarico, S. Curreri, F. Bonina, R. E. Perrotta. Evaluation of nanostructured lipid carriers (NLC) and nanoemulsions as carriers for UV-filters: characterization, in vitro penetration and photostability studies. Eur J Pharm Sci., 51 (2014), pp. 211-217.

R. L. Frozza, A. Bernardi, J. B. Hoppe, A. B. Meneghetti, A. M. O. Battastini, A. R. Pohlmann, S. S. Guterres, C. Salbego. Lipid-core nanocapsules improve the effects of resveratrol against Aβ-induced neuroinflammation. J Biomed Nanotechnol., 9 (2013), pp. 2086-2104.

I. C. Külkamp, B. D. Rabelo, S. J. Bertilz, M. Isoppo, M. D. Bianchin, S. R. Schaffazick, A. R. Pohlmann, S. S. Guterres. Nanoencapsulation improves the in vitro antioxidant activity of lipoic acid. J Biomed Nanotechnol., 7 (2011), pp. 598-607.

A. L. M. Silva, R. V. Contri, D. S. Jornada, A. R. Pohlmann, S. S. Guterres. Vitamin K1–loaded lipid‐core nanocapsules: physicochemical characterization and in vitro skin permeation. Skin Res Technol., 19 (2013), pp. e223-e230.

T. Katzer, P. Chaves, A. Bernardi, A. R. Pohlmann, S. S. Guterres, R. C. R. Beck. Prednisolone-loaded nanocapsules as ocular drug delivery system: development, in vitro drug release and eye toxicity. J Microencapsul., (2014), pp. 1-10.

N. P. Luepke. Hen’s eggs chorioallantoic membrane test for irritation potential. Food Chem Toxicol., 23 (1985), pp. 287–91.

R. V. Contri, T. Katzer, A. F. Ourique, A. L. M. Da Silva, R. C. R. Beck, A. R. Pohlmann, S. S. Guterres. Combined effect of polymeric nanocapsules and chitosan hydrogel on the increase of capsaicinoids adhesion to the skin surface. J Biomed Nanotechnol., 9 (2013), p. 1-11.

K. Paese, A. Jäger, F. S. Poletto, E. F. Pinto, B. Rossi-Bergmann, A. R. Pohlmann, S. S. Guterres. Semisolid formulation containing a nanoencapsulated sunscreen: effectiveness, in vitro photostability and immune response. J Biomed Nanotechnol., 5 (2009), pp. 240-246.

C. L. Sant’Anna, A. Tucci, M. T. P. Azevedo, S. S. Melcher, V. R. Werner, C. F. S. Malone, E. F. Rossini, F. R. Jacinavicius, G. S. Hentschke, J. A. S. Osti, K. R. S. Santos, W. A. Gama-Júnior, C. Rosal, G. Adame. Atlas de cianobactérias e microalgas de águas continentais brasileiras. Instituto de Botânica, São Paulo, (2012) 175 pp.

L. Zanella, M. A. Alam. Extracts and Bioactives from Microalgae (Sensu Stricto): Opportunities and Challenges for a New Generation of Cosmetics. In: Microalgae Biotechnology for Food, Health and High Value Products. Springer, Singapore (2020), pp. 295-349.

Hoshina, M. M. Hayakawa, M. Kobayashi, R. Higuchi, T. Suzaki. Pediludiella daitoensis gen. et sp. nov. (Scenedesmaceae, Chlorophyceae), a large coccoid green alga isolated from a Loxodes ciliate. Sci Rep., 10 (2020), pp. 1-13.

F. Akgül, İ. T. Kizilkaya, R. Akgül, H. Erduğan. Morphological and molecular characterization of Scenedesmus-like species from Ergene River Basin (Thrace, Turkey). Turk J Fish Aquat Sc.,17 (2017), pp. 609-619.

L. A. Fiel, K. Paese, M. Rizzi, S. S. Guterres, A. R. Pohlmann. A strategy to estimate the intrinsic flux of a poorly water-soluble substance for comparison with its release from lipid-core nanocapsules. Colloids Surf A Physicochem Eng Asp., 441 (2014), pp. 716-724.

M.-H. Schmid-Wendtner, H. C. Korting. The pH of the skin surface and its impact on the barrier function. Skin Pharmacol Physiol., 19 (2006), pp. 296-302.

M. D. Bianchin, I. C. Külkamp-Guerreiro, C. P. De Oliveira, R. V. Contri, S. S. Guterres, A. R. Pohlmann. Radar charts based on particle sizing as an approach to establish the fingerprints of polymeric nanoparticles in aqueous formulations. J Drug Deliv Sci Tec., 30 (2015), pp. 180-189.

J. Kockler, S. Robertson, M. Oelgemöller, M. Davies, B. Bowden, H. G. Brittain, B. D. Glass. Butyl methoxy dibenzoylmethane. In: Profiles of Drug Substances, Excipients and Related Methodology. Academic Press (2013), pp. 87-111.

C. P. Oliveira, C. G. Venturini, B. Donida, F. S. Poletto, S. S. Guterres, A. R. Pohlmann. An algorithm to determine the mechanism of drug distribution in lipid-core nanocapsule formulations. Soft Matter., 9 (2013), pp. 1141-1150.

R. C. R. Beck, A. F. Ourique, S. S. Guterres, A. R. Pohlmann. Spray-dried polymeric nanoparticles for pharmaceutics: a review of patents. Recent Pat Drug Deliv Formul., 6 (2012), pp. 195-208.

D. F. De Andrade, B. Vukosavljevic, J. B. Hoppe, A. R. Pohlmann, S. S. Guterres, M. Windbergs, I. C. Külkamp, C. G. Salbego, R. C. R. Beck. Redispersible Spray-Dried Powder Containing Nanoencapsulated Curcumin: The Drying Process Does Not Affect Neuroprotection In vitro. AAPS PharmSciTech., 20 (2019), p. 283.

M. C. L. Marchiori, A. F. Ourique, C. de B. da Silva, R. P. Raffin, A. R. Pohlmann, S. S. Guterres, R. C. R. Beck. Spray-Dried Powders Containing Tretinoin-Loaded Engineered Lipid-Core Nanocapsules: Development and Photostability Study. J Nanosci Nanotechnol. v. 11, n. 3, p. 1–9, 2012.

Z. A. Lewicka, A. F. Benedetto, D. N. Benoit, W. Y. William, J. D. Fortner, V. L. Colvin. The structure, composition, and dimensions of TiO2 and ZnO nanomaterials in commercial sunscreens. J Nanoparticle Res., 13 (2011), p. 3607.

R. E. M. Verdurmen, G. V. Houwelingen, M. Gunsing, M. Verschueren, J. Straatsma. Agglomeration in spray drying installations (the EDECAD project): Stickiness measurements and simulation results. Drying Technology., 24 (2006) pp. 721-726.

A. M. Cardoso, E. G. De Oliveira, K. Coradini, F. A. Bruinsmann, T. Aguirre, R. Lorenzoni, R. C. S. Barcelos, K. Roversi, D. R. Rossato, A. R. Pohlmann, S. S. Guterres, M. E. Burger, R. C. R. Beck. Chitosan hydrogels containing nanoencapsulated phenytoin for cutaneous use: Skin permeation/penetration and efficacy in wound healing. Mat Sci Eng C., 96 (2019), pp. 205-217.

R. V. Contri; R. M. Soares, A. R. Pohlmann, S. S. Guterres. Structural analysis of chitosan hydrogels containing polymeric nanocapsules. Mat Sci Eng C., 42 (2014), pp. 234-242.

W. Johnson Jr., W. Bergfeld, W. F. Belsito, D. V. Hill, R. A. Klaassen, C. D. Liebler, D. C.... & Gill, L. J. Safety Assessment of Lecithin and Other Phosphoglycerides as Used in Cosmetics. Int J Toxicol., 39 (2020), pp. 5S-25S.

NATIONAL CENTER FOR BIOTECHNOLOGY INFORMATION. Pubchem Database. Titanium dioxide. CID=26042. Disponível em: https://pubchem.ncbi.nlm.nih.gov/compound/Titanium-dioxide . Acesso em: 08 mar. 2020.

H. S. Stout, K. A. Murphy. Skin rejuvenation and defense system. U.S. Patent n. 9,925,137, 27 mar. 2018.

R. Lapasin. Rheological Caracterization of Hydrogels. In: P. Matricardi, F. Alhaique, T. Coviello. (Ed.). Polysaccharide hydrogels: Characterization and biomedical applications. CRC Press, 2016.

M. P. Alves, R. P. Raffin, S. B. Fagan. Rheological Behavior of Semisolid Formulations Containing Nanostructured Systems. In: Nanocosmetics and Nanomedicines. Springer Science & Business Media, (2011) pp. 37-45.

C. C. Bettoni, C. C. Felippi, C. De Andrade, R. P. Raffin, A. Jager, S. S. Guterres, T. D. Costa. Isotretinoin-loaded nanocapsules: stability and cutaneous penetration by tape stripping in human and pig skin. J Biomed Nanotechnol., 8 (2012), pp. 258-271.

F. C. Flores, J. A. De Lima, C. R. Da Silva, D. Benvegnú, J. Ferreira, M. E. Burger, R. C. R. Beck, C. M. B. Rolim, M. I. U. M. Rocha, M. L. Veiga, C. D. B. Da Silva. Hydrogels containing nanocapsules and nanoemulsions of tea tree oil provide antiedematogenic effect and improved skin wound healing. J Nanosci Nanotechnol., 15 (2015), pp. 800-809.

R. L. Pereira, F. I. Leites, K. Paese, R. M. Sponchiado, C. B. Michalowski, S. S. Guterres, E. E. Schapoval. Hydrogel containing adapalene-and dapsone-loaded lipid-core nanocapsules for cutaneous application: development, characterization, in vitro irritation and permeation studies. Drug Dev Ind Pharm., 42 (2016) pp. 2001-2008.

D. K. BABY. Rheology of hydrogels. In: Rheology of Polymer Blends and Nanocomposites. Elsevier, (2020) pp. 193-204.

F. C. Carvalho, G. Calixto, I. N. Hatakeyama, G. M. Luz, M. P. D. Gremião, M. Chorilli. Rheological, mechanical, and bioadhesive behavior of hydrogels to optimize skin delivery systems. Drug Dev Ind Pharm., 39 (2013) pp. 1750-1757.

Y. Chen. Properties and development of hydrogels. In: Hydrogels Based on Natural Polymers. Elsevier (2020), pp. 3-16.

C. Zuglianello, F. D. Andrade, P. S. Chaves, L. A. Rigo, A. R. Pohlmann, S. S. Guterres, R. C. R. Beck. Redispersible spray-dried nanocapsules for the development of skin delivery systems: proposing a novel blend of drying adjuvants. Soft Materials., 16 (2018), pp. 20-30.

T. Terroso, I. C. Külkamp, D. S. Jornada, A. R. Pohlmann, S. S. Guterres. Development of semi-solid cosmetic formulations containing coenzyme Q10-loaded nanocapsules. Lat Am J Pharm., 28 (2009) pp. 819-26.

A. C. H. R. Machado, P. S. Lopes, C. P. Raffier, I. N. Haridass, M. Roberts, J. Grice, V. R. Leite-Silva. Skin Penetration. In: Cosmetic Science and Technology: Theoretical Principles and Applications, (2017) pp. 741-755.

U. Osterwalder, M. Sohn, B. Herzog. Global state of sunscreens. Photodermatol Photoimmunol Photomed., 30 (2014), pp. 62-80.

S. Thiers, O. Tasseau. Les cosméceutiques: cosmétiques ou médicaments? Le MiDiFABs., 3 (2005), pp. 47-56.

S. S. Guterres, M. P. Alves, A. R. Pohlmann. Polymeric nanoparticles, nanospheres and nanocapsules, for cutaneous applications. Drug Target Insights, 2 (2007), pp. 147-157.

H. Gonzalez. Percutaneous absorption with emphasis on sunscreens. Photochem Photobiol Sci., 9 (2010) pp. 482-488.

J. S. SANTOS. Desenvolvimento de formulações contendo filtros solares nanoencapsulados. 2014 204 f. (Doutorado em Nanotecnologia Farmacêutica) – Universidade Federal do Rio Grande do Sul – RS, 2014.

A. C. Cozzi, P. Perugini, S. Gourion-Arsiquaud. Comparative behavior between sunscreens based on free or encapsulated UV filters in term of skin penetration, retention and photo-stability. Eur J Pharm Sci., 121 (2018), pp. 309-318.

A. Batista-Dhuarte, G. J. Murillo, J. E. Betancourt, P. Oliver, T. Damiana. The Hen’s Egg Test on Chorioallantoic Membrane: An alternative assay for the assessment of the irritating effect of vaccine adjuvants. Int J Toxicol., 35 (2016), pp. 627-633.

T. C. Barbosa, L. É. D. Nascimento, C. Bani, T. Almeida, M. Nery, R. S. Santos, L. R. O. Menezes, A. Zielinska, A. R. Fernandes, J. C. Cardoso, A. Jäger, E. Jäger, E. Sanchez-Lopez, L. Nalone, E. B. Souto, P. Severino. Development, Cytotoxicity and Eye Irritation Profile of a New Sunscreen Formulation Based on Benzophenone-3-poly (ε-caprolactone) Nanocapsules. Toxics, 7 (2019), pp. 1-12.

R. V. Contri, L. A. Fiel, N. Alnasif, A. R. Pohlmann, S. S. Guterres, M. Schäfer-Korting. Skin penetration and dermal tolerability of acrylic nanocapsules: influence of the surface charge and a chitosan gel used as vehicle. Int J Pharm., 507 (2016), p. 12-20.

S. K. JAIN, N. K. JAIN. Multiparticulate carriers for sun‐screening agents. Int J Cosmet Sci., 32 (2010), pp. 89-98.

C. B. Detoni, K. Paese, R. C. R. Beck, A. R. Pohlmann, S. S. Guterres. Nanosized and Nanoencapsulated Sunscreens. In: Nanocosmetics and Nanomedicines. Springer Science & Business Media, (2011) pp. 333-362.

S. R. Schaffazick, A. R. Pohlmann, T. Dalla-Costa, S. S. Guterres. Freeze-drying polymeric colloidal suspensions: nanocapsules, nanospheres and nanodispersion. A comparative study. Eur. J. Pharm. Biopharm., 56 (2003), pp. 501-505.

Downloads

Published

18-07-2025 — Updated on 30-03-2026

Versions

How to Cite

Almeida, G. F. de, Raffin Pohlmann, A., Paese, K., Mathes Faustino, S. M., Sato, M. S., Zatta, K. C., … Guterres, S. S. (2026). Hydrogels containing spray-dried avobenzone and resveratrol-loaded nanocapsules using titanium dioxide and microalgae as drying adjuvants: An innovative formulation for photoprotection. Drug Analytical Research, 9(1), 57–75. https://doi.org/10.22456/2527-2616.147538 (Original work published July 18, 2025)

Issue

Section

ORIGINAL ARTICLES