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However, their most notable advantage may be their ability to adhere to biological tissues. Many of these biopolymers have ionized forms, known as polyelectrolytes. When combined, polyelectrolytes with opposite charges spontaneously form polyelectrolyte complexes or multilayers, which have great functional versatility. Although only one natural polycation\u2014chitosan has been widely explored until now, it has been combined with many natural polyanions such as pectin, alginate and xanthan gum, among others. These polyelectrolyte complexes have been used to develop multiple mucoadhesive dosage forms such as hydrogels, tablets, microparticles, and films, which have demonstrated extraordinary potential to administer drugs by the ocular, nasal, buccal, oral, and vaginal routes, improving both local and systemic treatments. The advantages observed for these formulations include the increased bioavailability or residence time of the formulation in the administration zone, and the avoidance of invasive administration routes, leading to greater therapeutic compliance.<\/jats:p>","DOI":"10.3390\/polym13142241","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T21:05:54Z","timestamp":1625778354000},"page":"2241","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["Naturally Occurring Polyelectrolytes and Their Use for the Development of Complex-Based Mucoadhesive Drug Delivery Systems: An Overview"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8188-5001","authenticated-orcid":false,"given":"Ra\u00fal","family":"Cazorla-Luna","sequence":"first","affiliation":[{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araceli","family":"Mart\u00edn-Illana","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4151-1758","authenticated-orcid":false,"given":"Fernando","family":"Notario-P\u00e9rez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9925-5051","authenticated-orcid":false,"given":"Roberto","family":"Ruiz-Caro","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-Dolores","family":"Veiga","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia Gal\u00e9nica y Tecnolog\u00eda Alimentaria, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.apsb.2017.11.005","article-title":"Biomacromolecules as carriers in drug delivery and tissue engineering","volume":"8","author":"Zhang","year":"2018","journal-title":"Acta Pharm. 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