{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T05:58:14Z","timestamp":1778824694047,"version":"3.51.4"},"reference-count":53,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/04378\/2020; UIDB\/04378\/2020; LA\/P\/ 0140\/202019; LA\/P\/0037\/2020, UIDP\/50025\/2020, and UIDB\/50025\/2020"],"award-info":[{"award-number":["UIDP\/04378\/2020; UIDB\/04378\/2020; LA\/P\/ 0140\/202019; LA\/P\/0037\/2020, UIDP\/50025\/2020, and UIDB\/50025\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Solid microneedles (MNs) are effective transdermal delivery devices but are commonly fabricated from metallic or non-biodegradable materials, raising concerns related to sustainability, waste management, and processing constraints. This study aimed to evaluate the suitability of the biodegradable biopolyester poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate) (PHBHVHHx) as a structuring material for solvent-free fabrication of solid MN arrays and to assess their mechanical performance, insertion capability, and drug delivery potential. Methods: PHBHVHHx MN arrays were fabricated by solvent-free micromolding at 200 \u00b0C. The resulting MNs were morphologically characterized by scanning electron microscopy. Mechanical properties were assessed by axial compression testing, and insertion performance was evaluated using a multilayer Parafilm skin simulant model. Diclofenac sodium was used as a model drug and applied via surface coating using a FucoPol-based formulation. In vitro drug release was assessed in phosphate-buffered saline under sink conditions and quantified by UV\u2013Vis spectroscopy. Results: PHBHVHHx MN arrays consisted of sharp, well-defined conical needles (681 \u00b1 45 \u00b5m length; 330 \u00b5m base diameter) with micro-textured surfaces. The MNs withstood compressive forces up to 0.25 \u00b1 0.03 N\/needle and achieved insertion depths of approximately 396 \u00b5m in the Parafilm model. Drug-coated MNs retained adequate mechanical integrity and exhibited a rapid release profile, with approximately 73% of diclofenac sodium released within 10 min. Conclusions: The results demonstrate that PHBHVHHx is a suitable biodegradable thermoplastic for the fabrication of solid MN arrays via a solvent-free process. PHBHVHHx MNs combine adequate mechanical performance, reliable insertion capability, and compatibility with coated drug delivery, supporting their potential as sustainable alternatives to conventional solid MN systems.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010139","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T10:41:34Z","timestamp":1769164894000},"page":"139","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Solid Microneedles from Poly(3-hydroxybutyrate-co-3-hydroxyvalerate-co-3-hydroxyhexanoate): A Solvent-Free, Biodegradable Platform for Drug Delivery"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4376-6471","authenticated-orcid":false,"given":"Diana","family":"Ara\u00fajo","sequence":"first","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Chemistry, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4700-0476","authenticated-orcid":false,"given":"Francisco","family":"Santos","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Chemistry, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"CENIMAT\/i3N, Department of Materials Science, NOVA School of Science and Technology, NOVA University Lisbon, Campus de Caparica, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6608-3422","authenticated-orcid":false,"given":"Rui","family":"Igreja","sequence":"additional","affiliation":[{"name":"CENIMAT\/i3N, Department of Materials Science, NOVA School of Science and Technology, NOVA University Lisbon, Campus de Caparica, 2829-516 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9430-4640","authenticated-orcid":false,"given":"Filomena","family":"Freitas","sequence":"additional","affiliation":[{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Department of Chemistry, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, School of Science and Technology, NOVA University Lisbon, 2829-516 Caparica, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Aldawood, F.K., Andar, A., and Desai, S. (2021). A Comprehensive Review of Microneedles: Types, Materials, Processes, Characterizations and Applications. Polymers, 13.","DOI":"10.3390\/polym13162815"},{"key":"ref_2","first-page":"1800","article-title":"Microneedles Arrays: Based on Natural Polymers","volume":"Volume 2","author":"Freitas","year":"2019","journal-title":"Encyclopedia of Polymer Applications"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1007\/s10544-023-00658-y","article-title":"Microneedles: Materials, Fabrication, and Biomedical Applications","volume":"25","author":"Luo","year":"2023","journal-title":"Biomed. Microdevices"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1007\/s12247-021-09586-x","article-title":"A Review on Solid Microneedles for Biomedical Applications","volume":"17","author":"Tariq","year":"2022","journal-title":"J. Pharm. Innov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1124\/jpet.119.258707","article-title":"Microneedle Coating Methods: A Review with a Perspective","volume":"370","author":"Ingrole","year":"2019","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Rai, V.K., Saha, I., Alam, M., Nishchaya, K., Ghosh, G., and Rath, G. (2023). Microneedle Arrays for Cutaneous and Transcutaneous Drug Delivery, Disease Diagnosis, and Cosmetic Aid. J. Drug Deliv. Sci. Technol., 79.","DOI":"10.1016\/j.jddst.2022.104058"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kulkarni, D., Gadade, D., Chapaitkar, N., Shelke, S., Pekamwar, S., Aher, R., Ahire, A., Avhale, M., Badgule, R., and Bansode, R. (2023). Polymeric Microneedles: An Emerging Paradigm for Advanced Biomedical Applications. Sci. Pharm., 91.","DOI":"10.3390\/scipharm91020027"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.ijbiomac.2016.04.069","article-title":"Microbial Production of Polyhydroxyalkanoates (PHAs) and Its Copolymers: A Review of Recent Advancements","volume":"89","author":"Anjum","year":"2016","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dalton, B., Bhagabati, P., De Micco, J., Padamati, R.B., and O\u2019Connor, K. (2022). A Review on Biological Synthesis of the Biodegradable Polymers Polyhydroxyalkanoates and the Development of Multiple Applications. Catalysts, 12.","DOI":"10.3390\/catal12030319"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mel\u00e9ndez-Rodr\u00edguez, B., Torres-Giner, S., Reis, M.A.M., Silva, F., Matos, M., Cabedo, L., and Lagar\u00f3n, J.M. (2021). Blends of Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate) with Fruit Pulp Biowaste Derived Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate-Co-3-Hydroxyhexanoate) for Organic Recycling Food Packaging. Polymers, 13.","DOI":"10.3390\/polym13071155"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Pereira, J.R., Rafael, A.M., Esmail, A., Morais, M., Matos, M., Marques, A.C., Reis, M.A.M., and Freitas, F. (2023). Preparation of Porous Scaffold Based on Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate-Co-3-Hydroxyhexanoate) and FucoPol. Polymers, 15.","DOI":"10.3390\/polym15132945"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1002\/bit.22409","article-title":"Biosynthesis and Characterization of 3-Hydroxyalkanoate Terpolyesters with Adjustable Properties by Aeromonas hydrophila","volume":"104","author":"Zhang","year":"2009","journal-title":"Biotechnol. Bioeng."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1016\/j.procbio.2007.07.006","article-title":"Production and Characterization of Terpolyester Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate-Co-3-Hydroxyhexanoate) by Recombinant Aeromonas Hydrophila 4AK4 Harboring Genes phaAB","volume":"42","author":"Zhao","year":"2007","journal-title":"Process Biochem."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5856","DOI":"10.1021\/acsabm.0c00570","article-title":"Microneedle Arrays of Polyhydroxyalkanoate by Laser-Based Micromolding Technique","volume":"3","author":"Silvestre","year":"2020","journal-title":"ACS Appl. Bio Mater."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1039\/C7LC00016B","article-title":"Recent Advances in the Design of Polymeric Microneedles for Transdermal Drug Delivery and Biosensing","volume":"17","author":"Wang","year":"2017","journal-title":"Lab Chip"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yang, J., Zhang, H., Hu, T., Xu, C., Jiang, L., Shrike Zhang, Y., and Xie, M. (2021). Recent Advances of Microneedles Used towards Stimuli-Responsive Drug Delivery, Disease Theranostics, and Bioinspired Applications. Chem. Eng. J., 426.","DOI":"10.1016\/j.cej.2021.130561"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Eum, J., Kim, Y., Um, D., Shin, J., Yang, H., and Jung, H. (2021). Solvent-Free Polycaprolactone Dissolving Microneedles Generated via the Thermal Melting Method for the Sustained Release of Capsaicin. Micromachines, 12.","DOI":"10.3390\/mi12020167"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"16265","DOI":"10.3390\/s150716265","article-title":"Curved Microneedle Array-Based sEMG Electrode for Robust Long-Term Measurements and High Selectivity","volume":"15","author":"Kim","year":"2015","journal-title":"Sensors"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/adfm.201201512","article-title":"Composite Dissolving Microneedles for Coordinated Control of Antigen and Adjuvant Delivery Kinetics in Transcutaneous Vaccination","volume":"23","author":"DeMuth","year":"2013","journal-title":"Adv. Funct. Mater."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Silva, F., Matos, M., Pereira, B., Ralo, C., Pequito, D., Marques, N., Carvalho, G., and Reis, M.A.M. (2022). An Integrated Process for Mixed Culture Production of 3-Hydroxyhexanoate-Rich Polyhydroxyalkanoates from Fruit Waste. Chem. Eng. J., 427.","DOI":"10.1016\/j.cej.2021.131908"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.procbio.2018.09.001","article-title":"Effect of Mono- and Dipotassium Phosphate Concentration on Extracellular Polysaccharide Production by the Bacterium Enterobacter A47","volume":"75","author":"Pereira","year":"2018","journal-title":"Process Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/j.ijbiomac.2020.07.072","article-title":"Silver Nanocomposites Based on the Bacterial Fucose-Rich Polysaccharide Secreted by Enterobacter A47 for Wound Dressing Applications: Synthesis, Characterization and in Vitro Bioactivity","volume":"163","author":"Pereira","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ara\u00fajo, D., Martins, M., Conc\u00f3rdio-Reis, P., Roma-Rodrigues, C., Morais, M., Alves, V.D., Fernandes, A.R., and Freitas, F. (2023). Novel Hydrogel Membranes Based on the Bacterial Polysaccharide FucoPol: Design, Characterization and Biological Properties. Pharmaceuticals, 16.","DOI":"10.3390\/ph16070991"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.ijpharm.2014.05.042","article-title":"A Proposed Model Membrane and Test Method for Microneedle Insertion Studies","volume":"472","author":"Moore","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Silva, A.C.Q., Pereira, B., Lameirinhas, N.S., Costa, P.C., Almeida, I.F., Dias-Pereira, P., Correia-S\u00e1, I., Oliveira, H., Silvestre, A.J.D., and Vilela, C. (2023). Dissolvable Carboxymethylcellulose Microneedles for Noninvasive and Rapid Administration of Diclofenac Sodium. Macromol. Biosci., 23.","DOI":"10.1002\/mabi.202200323"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"D\u2019Arienzo, L., Acierno, S., Patti, A., and Di Maio, L. (2024). Cellulose\/Polyhydroxybutyrate (PHB) Composites as a Sustainable Bio-Based Feedstock to 3D-Printing Applications. Materials, 17.","DOI":"10.3390\/ma17040916"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.pnsc.2016.01.007","article-title":"Thermal Depolymerization Mechanisms of Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate)","volume":"26","author":"Xiang","year":"2016","journal-title":"Prog. Nat. Sci. Mater. Int."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Karim, Z., Karwa, P., and Hiremath, S.R.R. (2022). Polymeric Microneedles for Transdermal Drug Delivery- a Review of Recent Studies. J. Drug Deliv. Sci. Technol., 77.","DOI":"10.1016\/j.jddst.2022.103760"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"945","DOI":"10.2147\/DDDT.S44401","article-title":"Dissolving and Biodegradable Microneedle Technologies for Transdermal Sustained Delivery of Drug and Vaccine","volume":"7","author":"Yuan","year":"2013","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.msec.2016.03.097","article-title":"A Fabrication Method of Microneedle Molds with Controlled Microstructures","volume":"65","author":"Wang","year":"2016","journal-title":"Mater. Sci. Eng. C"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ando, D., Miyatsuji, M., Sakoda, H., Yamamoto, E., Miyazaki, T., Koide, T., Sato, Y., and Izutsu, K. (2024). Mechanical Characterization of Dissolving Microneedles: Factors Affecting Physical Strength of Needles. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16020200"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1039\/D4PM00024B","article-title":"In Vitro Evaluation of Microneedle Strength: A Comparison of Test Configurations and Experimental Insights","volume":"1","author":"Alrimawi","year":"2024","journal-title":"RSC Pharm."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kang, S., Song, J.E., Jun, S.-H., Park, S.-G., and Kang, N.-G. (2022). Sugar-Triggered Burst Drug Releasing Poly-Lactic Acid (PLA) Microneedles and Its Fabrication Based on Solvent-Casting Approach. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14091758"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s40820-021-00611-9","article-title":"Engineering Microneedle Patches for Improved Penetration: Analysis, Skin Models and Factors Affecting Needle Insertion","volume":"13","author":"Makvandi","year":"2021","journal-title":"Nano-Micro Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.actbio.2021.08.045","article-title":"Insights into the Mechanics of Solid Conical Microneedle Array Insertion into Skin Using the Finite Element Method","volume":"135","author":"Shu","year":"2021","journal-title":"Acta Biomater."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhou, C., Chen, T., Jiang, Z., Lu, C., Wu, C., Pan, X., Huang, Z., and Peng, T. (2024). State-of-the-Art Strategies to Enhance the Mechanical Properties of Microneedles. Int. J. Pharm., 663.","DOI":"10.1016\/j.ijpharm.2024.124547"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Shah, S.A., Oakes, R.S., Kapnick, S.M., and Jewell, C.M. (2022). Mapping the Mechanical and Immunological Profiles of Polymeric Microneedles to Enable Vaccine and Immunotherapy Applications. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.843355"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Demir, Y.K., Akan, Z., and Kerimoglu, O. (2013). Characterization of Polymeric Microneedle Arrays for Transdermal Drug Delivery. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077289"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.jconrel.2005.02.002","article-title":"Biodegradable Polymer Microneedles: Fabrication, Mechanics and Transdermal Drug Delivery","volume":"104","author":"Park","year":"2005","journal-title":"J. Control. Release"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Fonseca, D.F.S., Vilela, C., Pinto, R.J.B., Bastos, V., Oliveira, H., Catarino, J., Fa\u00edsca, P., Rosado, C., Silvestre, A.J.D., and Freire, C.S.R. (2021). Bacterial Nanocellulose-Hyaluronic Acid Microneedle Patches for Skin Applications: In Vitro and in Vivo Evaluation. Mater. Sci. Eng. C, 118.","DOI":"10.1016\/j.msec.2020.111350"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sabri, A.H., Cater, Z., Ogilvie, J., Scurr, D.J., Marlow, M., and Segal, J. (2020). Characterisation of Mechanical Insertion of Commercial Microneedles. J. Drug Deliv. Sci. Technol., 58.","DOI":"10.1016\/j.jddst.2020.101766"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1159\/000497475","article-title":"Noninvasive Determination of Epidermal and Stratum Corneum Thickness in Vivo Using Two-Photon Microscopy and Optical Coherence Tomography: Impact of Body Area, Age, and Gender","volume":"32","author":"Czekalla","year":"2019","journal-title":"Ski. Pharmacol. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Dawud, H., and Abu Ammar, A.A. (2023). Rapidly Dissolving Microneedles for the Delivery of Steroid-Loaded Nanoparticles Intended for the Treatment of Inflammatory Skin Diseases. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020526"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez-Cendal, A.I., G\u00f3mez-Seoane, I., de Toro-Santos, F.J., Fuentes-Boquete, I.M., Se\u00f1ar\u00eds-Rodr\u00edguez, J., and D\u00edaz-Prado, S.M. (2023). Biomedical applications of the biopolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV): Drug encapsulation and scaffold fabrication. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241411674"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.ijbiomac.2015.05.029","article-title":"Rheological Studies of the Fucose-Rich Exopolysaccharide FucoPol","volume":"79","author":"Torres","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.jconrel.2017.03.383","article-title":"Fabrication of Coated Polymer Microneedles for Transdermal Drug Delivery","volume":"265","author":"Chen","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wu, L., Shrestha, P., Iapichino, M., Cai, Y., Kim, B., and Stoeber, B. (2021). Characterization Method for Calculating Diffusion Coefficient of Drug from Polylactic Acid (PLA) Microneedles into the Skin. J. Drug Deliv. Sci. Technol., 61.","DOI":"10.1016\/j.jddst.2020.102192"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Keirouz, A., Mustafa, Y.L., Turner, J.G., Lay, E., Jungwirth, U., Marken, F., and Leese, H.S. (2023). Conductive Polymer-Coated 3D Printed Microneedles: Biocompatible Platforms for Minimally Invasive Biosensing Interfaces. Small, 19.","DOI":"10.1002\/smll.202206301"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"6808","DOI":"10.1039\/C8TB01476K","article-title":"Bioceramic Microneedle Arrays Are Able to Deliver OVA to Dendritic Cells in Human Skin","volume":"6","author":"Vallhov","year":"2018","journal-title":"J. Mater. Chem. B"},{"key":"ref_50","first-page":"612","article-title":"Enhanced Delivery Efficiency and Sustained Release of Biopharmaceuticals by Complexation-Based Gel Encapsulated Coated Microneedles: rhIFN\u03b1-1b Example","volume":"16","author":"Zhou","year":"2021","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Carvalho, J.P.F., Silva, A.C.Q., Bastos, V., Oliveira, H., Pinto, R.J.B., Silvestre, A.J.D., Vilela, C., and Freire, C.S.R. (2020). Nanocellulose-Based Patches Loaded with Hyaluronic Acid and Diclofenac towards Aphthous Stomatitis Treatment. Nanomaterials, 10.","DOI":"10.3390\/nano10040628"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1021\/acs.molpharmaceut.4c01058","article-title":"In vitro drug release and ex vivo dermal drug permeation studies of selected commercial benzoyl peroxide topical formulations: Correlation between human and porcine skin models","volume":"22","author":"Brighenti","year":"2025","journal-title":"Mol. Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Monou, P.K., Andriotis, E.G., Bouropoulos, N., Panteris, E., Akrivou, M., Vizirianakis, I.S., Ahmad, Z., and Fatouros, D.G. (2021). Engineered mucoadhesive microparticles of formoterol\/budesonide for pulmonary administration. Eur. J. Pharm. Sci., 165.","DOI":"10.1016\/j.ejps.2021.105955"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/1\/139\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T05:26:07Z","timestamp":1769491567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/18\/1\/139"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,22]]},"references-count":53,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["pharmaceutics18010139"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics18010139","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,22]]}}}