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Chitosan in endometriosis pain treatment

Chronic, painful diseases such as endometriosis can lead to a severe reduction in the quality of life of those affected. Drug delivery systems, such as chitosan-containing hydrogels, could enable efficient pain management with prolonged and targeted drug release. Therefore, in the study presented here, hydrogels made of chitosan and the vanillin derivative 2-hydroxy-5-nitrobenzaldehyde were investigated as a drug delivery system for diclofenac sodium salt.


Prospects and Challenges of the Drug Delivery Systems in Endometriosis Pain Management: Experimental and Theoretical Aspects. Toma, B.F.; Socolov, R.; Popa, O.; Socolov, D.; Nica, I.; Agop, M.; Vasincu, D.; Grigore, M.; Ochiuz, L.; Journal of Immunology Research, Res. 2021 Dec 15;2021:2727174. doi:

Endometriosis is a usually benign, chronic, inflammatory disease of women of fertile age. Due to the presence of glandular stromal tissue outside the uterus, the disease often shows a very painful course. This leads to a severe loss of quality of life of patients.
For this reason, pain management plays an important role in addition to drug and surgical treatment of the disease. Non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac are often used for this purpose. In addition to its analgesic effect, it also has an anti-inflammatory effect by inhibiting COX-1 and COX-2 receptors. However, drugs like diclofenac (DCF) have renal, cardiovascular, and gastrointestinal side effects. To reduce these while also achieving a targeted effect with better bioavailability, drug delivery systems can be used. Hydrogels made from natural substances such as chitosan are particularly promising due to their good biocompatibility, biodegradability and natural antimicrobial properties.These effects can be further enhanced by crosslinking with aldehydes of similar properties, e.g. the vanillin derivative 2-hydroxy-5-nitrobenzyaldide.  For this reason, hydrogels of chitosan and 2-hydroxy-5-nitrobenzyaldyde were investigated as drug delivery systems for targeted drug release for DCF in the presented study. Four different formulations with different amine-aldehyde ratios were tested to assess the influence of the intermolecular interactions of the molecules on drug release. In addition, a mathematical model was created to better analyze the drug delivery mechanism in the future.


  • Evidence of homogeneous distribution of the active ingredient in the pores of the gel via SEM (scanning electron microscopy) and POM (polarized light microscopy) for all formulations
  • The degree of crosslinking of the chitosan has no influence on the microstructure of the formulations
  • Pulsatile in vitro release of DCF independent of the crosslinking of the chitosan
  • Hydrogel with the lowest degree of crosslinking showed the fastest drug release over 9 days
  • But: higher crosslinking showed faster release than the formulations with intermediate crosslinking → No correlation of crosslinking degree and duration of drug release
  • However, continuous release of DCF was demonstrated for all formulations over the time period studied
  • Mathematical model for drug release fits the obtained model
  • Saturation with DCF reached after 24-28 h

Conclusion: In the DCF-containing hydrogels of chitosan and 2-hydroxy-5-nitrobenzaldehyde prepared in the study, uniform drug distribution in the pores of the hydrogel was demonstrated via SEM and POM. Moreover, prolonged and continuous release of DCF occurred in vitro over a period of 9 days. However, no correlation was observed between drug release and crosslinking of the chitosan, which was probably due to different sized DCF crystals in the hydrogel pores. Overall, however, it could be concluded that the development of drug delivery systems could offer a perspective for pain management of chronic diseases such as endometriosis. Link to article:

drug delivery, chitosan, hydrogels, endometriosis

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