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| Author(s): |
Silvia Vaz Guerra Nista
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Engenharia Química |
| Defense date: | 2016-04-14 |
| Examining board members: |
Lúcia Helena Innocentini Mei;
Ronaldo Aloise Pilli;
Michelle Franz Montan;
Andre Luis Ferrari de Moura Giraldi;
Rosario Elida Suman Bretas
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| Advisor: | Lúcia Helena Innocentini Mei |
| Abstract | |
This project was dedicated to the development and characterization of a mucoadhesive system of high performance adhesion, based on electrospun membranes made of mucoadhesive polymer solutions for oral release of active ingredients. Its development was carried on in three phases. The first was devoted to obtain electrospun nanofibers membranes with individual mucoadhesive polymers, like Alginate/PEO and Chitosan/PEO, and with their their mixtures (chitosan/PEO + Alginate/PEO). Membranes of Alginate/PEO, Chitosan/PEO and also Cellulose Acetate (CA) were loaded with 10 and 20% w/w of drug metronidazole (MTZ), an antibiotic widely used in the treatment of periodontitis. The CA membranes were coated with nanofiber of mucoadhesive polymers by layer-by-layer technique, yielding an additional controlled release device. All nanofibers prepared showed no defects such as beads and presented a homogeneous distribution of the diameter. Excellent results were obtained for crosslinking the nanofiber membranes SA/PEO and CA-coated SA/PEO. These membranes, after the new technique developed of dry crosslinking of SA/PEO by atomization using CaCl2 and subsequent atomization of chitosan solution, showed a weight loss of only 41% after 24 hours at 37 ° C in simulated body fluid solutions. In the second phase, microbiological analysis was carried out to verify the drug efficiency in the membrane after the electrospinning process using anaerobic gram negative bacterium, A. actinomycetemcomitans, a metronidazole sensitive drug and present in periodontal pockets. Through the cell viability tests with Trypan Blue assay was found that the incorporation of 10% MTZ produced biocompatible membranes.The controlled release of Metronidazole in vitro was evaluated and the membranes of SA/PEO and of CA coated with SA/PEO showed the best results of drug release, with the lowest burst effect compared to other membranes tested. The permeation test across the porcine oral mucosa was measured in order to evaluate the barrier function of the membranes and showed that the two CA coated membranes presented similar profiles; Lag time and Steady state flux values were lower than the uncoated membranes. The third phase of the project allowed us to determine the best mucoadhesive membrane for drug release, through the final tests of mucoadhesion performance by adsorption of Mucin, time and mucoadhesion force that simulate the actual conditions of application of the devices developed in the oral cavity. The SA/PEO nanofiber membranes were the most suitable for the proposed application in periodontal diseases. It presented homogeneous nanofiber and free of defects. The release profile was suitable for the drug with and without epithelial barrier. The results of the citotoxic tests showed that the membranes are biocompatible. The membranes had the best results in Time and mucoadhesion Force, surpassing the results of the other membranes (AU) | |
| FAPESP's process: | 12/11904-5 - High adhesive nanofibers membrane to oral delivery of drugs. |
| Grantee: | Silvia Vaz Guerra Nista |
| Support Opportunities: | Scholarships in Brazil - Doctorate |