CoChat
Sign Up
Cited by 18Advanced Drug Delivery SystemsHydrogels: synthesis, properties, applicationsPolymer-Based Agricultural Enhancements

Evaluating Non-Conventional Chitosan Sources for Controlled Release of Risperidone

Open access
Garcinuño, Sara, Aranaz, Inmaculada, Civera, Concepción, Arias, Concepción, Acosta, Niuris·2022·Polymers
DOI 10.3390/polym14071355PMC PMC9002647
Open this paper in CoChat — free accountOpen PDF

Abstract

In this work, two chitosan samples from cuttlebone and squid pen are produced and characterized. We studied the formation of thermoresponsive hydrogels with β-glycerol phosphate and found proper formulations that form the hydrogels at 37 °C. Gel formation depended on the chitosan source being possible to produce the thermoresponsive hydrogels at chitosan concentration of 1% with cuttlebone chitosan but 1.5% was needed for squid pen. For the first time, these non-commercial chitosan sources have been used in combination with β-glycerol phosphate to prepare risperidone formulations for controlled drug delivery. Three types of formulations for risperidone-controlled release have been developed, in-situ gelling formulations, hydrogels and xerogels. The release profiles show that in-situ gelling formulations and particularly hydrogels allow an extended control release of risperidone while xerogels are not appropriate formulations for this end since risperidone was completely released in 48 h.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/polym14071355

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • β-Chitosan hydrogels and coatings are highly effective as injectable anti-adhesion materials, particularly for laparoscopic surgeries.

    “This makes β-chitosan hydrogels and coatings highly effective as injectable anti-adhesion materials, particularly for laparoscopic surgeries [160,161].”

    From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [161]

    The Introduction and Methods describe β-chitosan hydrogels and formulations intended for injection. The paper studies risperidone delivery, however; it does not establish that hydrogels or coatings are effective against surgical adhesions, or discuss laparoscopic surgery. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 46

  1. [1]Kurita K. Controlled Functionalization of the Polysaccharide Chitin Prog. Polym. Sci. 2001 26 1921 1971 10.1016/S0079-6700(01)00007-7 · DOI
  2. [2]Rinaudo M. Chitin and Chitosan: Properties and Applications Prog. Polym. Sci. 2006 31 603 632 10.1016/j.progpolymsci.2006.06.001 · DOI
  3. [3]Younes I. Rinaudo M. Harding D. Sashiwa H. Marine Drugs Chitin and Chitosan Preparation from Marine Sources. Structure, Properties and Applications Mar. Drugs 2015 13 1133 1174 10.3390/md13031133 25738328 PMC4377977 · DOI
  4. [4]Rodríguez-Vázquez M. Vega-Ruiz B. Ramos-Zúñiga R. Saldaña-Koppel D.A. Fernando Quiñones-Olvera L. Piraino F. Chitosan and Its Potential Use as a Scaffold for Tissue Engineering in Regenerative Medicine BioMed Res. Int. 2015 2015 821279 10.1155/2015/821279 26504833 PMC4609393 · DOI
  5. [5]Lall A. Tamo A.K. Doench I. David L. Nunes De Oliveira P. Gorzelanny C. Osorio-Madrazo A. Nanoparticles and Colloidal Hydrogels of Chitosan-Caseinate Polyelectrolyte Complexes for Drug-Controlled Release Applications Int. J. Mol. Sci. 2020 21 5602 10.3390/ijms21165602 PMC7460567 32764340 · DOI
  6. [6]Peers S. Montembault A. Ladavière C. Chitosan Hydrogels for Sustained Drug Delivery J. Control. Release 2020 326 150 163 10.1016/j.jconrel.2020.06.012 32562854 · DOI
  7. [7]Wu D. Zhu L. Li Y. Zhang X. Xu S. Yang G. Delair T. Chitosan-Based Colloidal Polyelectrolyte Complexes for Drug Delivery: A Review Carbohydr. Polym. 2020 238 116126 10.1016/j.carbpol.2020.116126 32299572 · DOI
  8. [8]Chenite A. Buschmann M. Wang D. Chaput C. Kandani N. Rheological Characterisation of Thermogelling Chitosan/Glycerol-Phosphate Solutions Carbohydr. Polym. 2001 46 39 47 10.1016/S0144-8617(00)00281-2 · DOI
  9. [9]Rahmanian-Devin P. Rahimi V.B. Askari V.R. Thermosensitive Chitosan-β-Glycerophosphate Hydrogels as Targeted Drug Delivery Systems: An Overview on Preparation and Their Applications Adv. Pharmacol. Pharm. Sci. 2021 2021 6640893 10.1155/2021/6640893 34036263 PMC8116164 · DOI
  10. [10]Amin S. Alaa El-Din B. Zhifa S. Azam A. Injectable Gel from Squid Pen Chitosan for Bone-Tissue Engineering Applications Front. Bioeng. Biotechnol. 2016 4 1454 10.3389/conf.FBIOE.2016.01.01454 · DOI
  11. [11]Ngoenkam J. Faikrua A. Yasothornsrikul S. Viyoch J. Potential of an Injectable Chitosan/Starch/β-Glycerol Phosphate Hydrogel for Sustaining Normal Chondrocyte Function Int. J. Pharm. 2010 391 115 124 10.1016/j.ijpharm.2010.02.028 20206248 · DOI
  12. [12]Tsai M.L. Chang H.W. Yu H.C. Lin Y.S. Tsai Y.D. Effect of Chitosan Characteristics and Solution Conditions on Gelation Temperatures of Chitosan/2-Glycerophosphate/Nanosilver Hydrogels Carbohydr. Polym. 2011 84 1337 1343 10.1016/j.carbpol.2011.01.035 · DOI
  13. [14]Salarvand M. Ramezani V. Salarvand F. Darabi Z.A. Akrami M. Improvement of Drug Delivery Properties of Risperidone via Preparation of Fast Dissolution Tablet Containing Nanostructured Microparticles Iran. J. Pharm. Res. 2021 20 183 196 10.22037/ijpr.2020.112230.13621 34567155 PMC8457718 · DOI
  14. [15]Elena de Souza L. Eckenstaler R. Syrowatka F. Beck-Broichsitter M. Benndorf R.A. Mäder K. Has PEG-PLGA Advantages for the Delivery of Hydrophobic Drugs? Risperidone as an Example J. Drug Deliv. Sci. Technol. 2021 61 102239 10.1016/j.jddst.2020.102239 · DOI
  15. [16]Lugasi L. Grinberg I. Sabag R. Madar R. Einat H. Margel S. Molecules Proteinoid Nanocapsules as Drug Delivery System for Improving Antipsychotic Activity of Risperidone Molecules 2020 25 4013 10.3390/molecules25174013 PMC7504754 32887463 · DOI
  16. [17]Bellotti E. Contarini G. Geraci F. Torrisi S.A. Piazza C. Drago F. Leggio G.M. Papaleo F. Decuzzi P. Long-Lasting Rescue of Schizophrenia-Relevant Cognitive Impairments via Risperidone-Loaded MicroPlates Drug Deliv. Transl. Res. 2022 10.1007/s13346-021-01099-x PMC9242964 34973133 · DOI
  17. [18]Chen F. Liu H. Wang B. Yang L. Cai W. Jiao Z. Yang Z. Chen Y. Quan Y. Xiang X. Physiologically Based Pharmacokinetic Modeling to Understand the Absorption of Risperidone Orodispersible Film Front. Pharmacol. 2020 10 1692 10.3389/fphar.2019.01692 32116683 PMC7008171 · DOI
  18. [19]Rukmangathen R. Yallamalli I.M. Yalavarthi P.R. Formulation and Biopharmaceutical Evaluation of Risperidone-Loaded Chitosan Nanoparticles for Intranasal Delivery Drug Dev. Ind. Pharm. 2019 45 1342 1350 10.1080/03639045.2019.1619759 31094571 · DOI
  19. [20]Kumar M. Pathak K. Misra A. Formulation and Characterization of Nanoemulsion-Based Drug Delivery System of Risperidone Drug Dev. Ind. Pharm. 2009 35 387 395 10.1080/03639040802363704 19016058 · DOI
  20. [21]Siafaka P.I. Barmpalexis P. Lazaridou M. Papageorgiou G.Z. Koutris E. Karavas E. Kostoglou M. Bikiaris D.N. Controlled Release Formulations of Risperidone Antipsychotic Drug in Novel Aliphatic Polyester Carriers: Data Analysis and Modelling Eur. J. Pharm. Biopharm. 2015 94 473 484 10.1016/j.ejpb.2015.06.027 26159838 · DOI
  21. [22]Silva A.C. Amaral M.H. González-Mira E. Santos D. Ferreira D. Solid Lipid Nanoparticles (SLN)—Based Hydrogels as Potential Carriers for Oral Transmucosal Delivery of Risperidone: Preparation and Characterization Studies Colloids Surf. B Biointerfaces 2012 93 241 248 10.1016/j.colsurfb.2012.01.014 22293602 · DOI
  22. [23]Badshah A. Subhan F. Rauf K. Irfan Bukhari N. Shah K. Khan S. Ahmed Z. Khan I. Development of Controlled-Release Matrix Tablet of Risperidone: Influence of Methocel®- and Ethocel®-Based Novel Polymeric Blend on In Vitro Drug Release and Bioavailability AAPS PharmSciTech 2011 12 525 533 10.1208/s12249-011-9613-2 21494924 PMC3134665 · DOI
  23. [24]Silva A.C. Kumar A. Wild W. Ferreira D. Santos D. Forbes B. Long-Term Stability, Biocompatibility and Oral Delivery Potential of Risperidone-Loaded Solid Lipid Nanoparticles Int. J. Pharm. 2012 436 798 805 10.1016/j.ijpharm.2012.07.058 22867992 · DOI
  24. [25]Nanaki S. Barmpalexis P. Iatrou A. Christodoulou E. Kostoglou M. Bikiaris D. Risperidone Controlled Release Microspheres Based on Poly(Lactic Acid)-Poly(Propylene Adipate) Novel Polymer Blends Appropriate for Long Acting Injectable Formulations Pharmaceutics 2018 10 130 10.3390/pharmaceutics10030130 PMC6161267 30104505 · DOI
  25. [26]D’Souza S. Faraj J.A. Giovagnoli S. DeLuca P.P. Development of Risperidone PLGA Microspheres J. Drug Deliv. 2014 2014 1 11 10.1155/2014/620464 PMC3927762 24616812 · DOI
  26. [27]Arrouze F. Desbrieres J. Lidrissi Hassani S. Tolaimate A. Investigation of β-Chitin Extracted from Cuttlefish: Comparison with Squid β-Chitin Polym. Bull. 2021 78 7219 7239 10.1007/s00289-020-03466-z · DOI
  27. [28]Galed G. Diaz E. Goycoolea F.M. Heras A. Influence of N-Deacetylation Conditions on Chitosan Production from α-Chitin Nat. Prod. Commun. 2008 3 1934578X0800300414 10.1177/1934578X0800300414 · DOI
  28. [29]Muzzarelli R.A.A. Rocchetti R. Determination of the Degree of Acetylation of Chitosans by First Derivative Ultraviolet Spectrophotometry Carbohydr. Polym. 1985 5 461 472 10.1016/0144-8617(85)90005-0 · DOI
  29. [30]Rinaudo M. Milas M. Le Dung P. Characterization of Chitosan. Influence of Ionic Strength and Degree of Acetylation on Chain Expansion Int. J. Biol. Macromol. 1993 15 281 285 10.1016/0141-8130(93)90027-J 8251442 · DOI
  30. [31]Zhang Y. Xue C. Xue Y. Gao R. Zhang X. Determination of the Degree of Deacetylation of Chitin and Chitosan by X-ray Powder Diffraction Carbohydr. Res. 2005 340 1914 1917 10.1016/j.carres.2005.05.005 15963961 · DOI
  31. [32]Cuong H.N. Minh N.C. van Hoa N. Trung T.S. Preparation and Characterization of High Purity β-Chitin from Squid Pens (Loligo Chenisis) Int. J. Biol. Macromol. 2016 93 442 447 10.1016/j.ijbiomac.2016.08.085 27593242 · DOI
  32. [33]Abdou E.S. Nagy K.S.A. Elsabee M.Z. Extraction and Characterization of Chitin and Chitosan from Local Sources Bioresour. Technol. 2008 99 1359 1367 10.1016/j.biortech.2007.01.051 17383869 · DOI
  33. [34]Zhou H.Y. Chen X.G. Kong M. Liu C.S. Cha D.S. Kennedy J.F. Effect of Molecular Weight and Degree of Chitosan Deacetylation on the Preparation and Characteristics of Chitosan Thermosensitive Hydrogel as a Delivery System Carbohydr. Polym. 2008 73 265 273 10.1016/j.carbpol.2007.11.026 · DOI
  34. [35]Branca C. D’Angelo G. Crupi C. Khouzami K. Rifici S. Ruello G. Wanderlingh U. Role of the OH and NH Vibrational Groups in Polysaccharide-Nanocomposite Interactions: A FTIR-ATR Study on Chitosan and Chitosan/Clay Films Polymer 2016 99 614 622 10.1016/j.polymer.2016.07.086 · DOI
  35. [36]Gutiérrez M.C. García-Carvajal Z.Y. Jobbágy M. Rubio F. Yuste L. Rojo F. Ferrer M.L. del Monte F. Poly(Vinyl Alcohol) Scaffolds with Tailored Morphologies for Drug Delivery and Controlled Release Adv. Funct. Mater. 2007 17 3505 3513 10.1002/adfm.200700093 · DOI
  36. [37]Wu I.Y. Bala S. Škalko-Basnet N. di Cagno M.P. Interpreting Non-Linear Drug Diffusion Data: Utilizing Korsmeyer-Peppas Model to Study Drug Release from Liposomes Eur. J. Pharm. Sci. 2019 138 105026 10.1016/j.ejps.2019.105026 31374254 · DOI · Paper page
  37. [38]Higuchi T. Rate of Release of Medicaments from Ointment Bases Containing Drugs in Suspension J. Pharm. Sci. 1961 50 874 875 10.1002/jps.2600501018 13907269 · DOI
  38. [39]Siepmann J. Peppas N.A. Higuchi Equation: Derivation, Applications, Use and Misuse Int. J. Pharm. 2011 418 6 12 10.1016/j.ijpharm.2011.03.051 21458553 · DOI
  39. [40]Papadopoulou V. Kosmidis K. Vlachou M. Macheras P. On the Use of the Weibull Function for the Discernment of Drug Release Mechanisms Int. J. Pharm. 2006 309 44 50 10.1016/j.ijpharm.2005.10.044 16376033 · DOI · Paper page
  40. [41]Kamdem Tamo A. Doench I. Morales Helguera A. Hoenders D. Walther A. Madrazo A.O. Biodegradation of Crystalline Cellulose Nanofibers by Means of Enzyme Immobilized-Alginate Beads and Microparticles Polymers 2020 12 1522 10.3390/polym12071522 PMC7407417 32660071 · DOI
  41. [42]Ramasamy P. Subhapradha N. Shanmugam V. Shanmugam A. Extraction, Characterization and Antioxidant Property of Chitosan from Cuttlebone Sepia Kobiensis (Hoyle 1885) Int. J. Biol. Macromol. 2014 64 202 212 10.1016/j.ijbiomac.2013.12.008 24333227 · DOI
  42. [43]Shushizadeh M.R. Pour E.M. Zare A. Lashkari Z. Persian Gulf β-Chitin Extraction from Sepia Pharaonis Sp. Cuttlebone and Preparation of Its Derivatives Bioact. Carbohydr. Diet. Fibre 2015 6 133 142 10.1016/j.bcdf.2015.09.003 · DOI
  43. [44]Aranaz I. Alcántara A.R. Civera M.C. Arias C. Elorza B. Caballero A.H. Acosta N. Velasco H. Mecerreyes D. Antonio R. Polymers Chitosan: An Overview of Its Properties and Applications Polymers 2021 13 3256 10.3390/polym13193256 34641071 PMC8512059 · DOI
  44. [45]Kolawole O.M. Lau W.M. Khutoryanskiy V.V. Chitosan/β-Glycerophosphate In Situ Gelling Mucoadhesive Systems for Intravesical Delivery of Mitomycin-C Int. J. Pharm. 2019 1 100007 10.1016/j.ijpx.2019.100007 PMC6733296 31517272 · DOI
  45. [46]Gutiérrez M.C. Ferrer M.L. del Monte F. Ice-Templated Materials: Sophisticated Structures Exhibiting Enhanced Functionalities Obtained after Unidirectional Freezing and Ice-Segregation-Induced Self-Assembly Chem. Mater. 2008 20 634 648 10.1021/cm702028z · DOI
  46. [47]Ebrahimi A. Sadrjavadi K. Hajialyani M. Shokoohinia Y. Fattahi A. Preparation and Characterization of Silk Fibroin Hydrogel as Injectable Implants for Sustained Release of Risperidone Drug Dev. Ind. Pharm. 2018 44 199 205 10.1080/03639045.2017.1386195 28956466 · DOI

Cited by

Sorted by citations

Authors
Garcinuño, S., Aranaz, I., Civera, C., Arias, C., & Acosta, N.
Affiliations
Universidad Complutense de Madrid (ES)
Corresponding author
  • Aranaz, Inmaculada
  • Acosta, Niuris
ORCID
Venue
Polymers
Publisher
MDPI AG
Published
2022-03-26
Volume
14
Issue
7
Pages
1355
ISSN
2073-4360 (ISSN-L)
DOI
10.3390/polym14071355
PMC
PMC9002647
OpenAlex
W4220779430
Cited by
18
References
0
Citations by year
2026: 6 · 2025: 4 · 2024: 2 · 2023: 3 · 2022: 3
FWCI
1.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Polymers (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Ministerio de Ciencia e Innovacion, España (PID2019-105337RB-C22)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Physical Sciences › Engineering › Biomedical Engineering › Polymer-Based Agricultural Enhancements
Keywords
chitosan, cuttlebone, squid pen, risperidone, controlled drug release, thermosensitive hydrogel, β-glycerol phosphate, in situ gelling, xerogels, antipsychotic drug delivery

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review