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| Author(s): |
Louise Lacalendola Tundisi
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Farmacêuticas |
| Defense date: | 2022-02-11 |
| Examining board members: |
Priscila Gava Mazzola;
Frederico Pittella Silva;
Marlus Chorilli;
Daniele Ribeiro de Araujo;
Renata Fonseca Vianna Lopez
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| Advisor: | Priscila Gava Mazzola |
| Abstract | |
Topical route brings many advantages over oral treatment, since there is no first-pass effect, less or no drug interactions and usually does not require laboratory monitoring during treatment. As an improvement in topical drug delivery effectiveness, the investigation of new pharmaceutical formulation is mandatory for increasing patient compliance, by easing the therapeutic regime. In this context, the aim of this proposal is to study a drug delivery system capable to modulate topical drug release using a stimuli-responsive polymer with casein and evaluating the the addition of polymeric nanoparticles to the hydrogel rheological modulation and drug delivery enhance. We formulated combinations of P407 and casein in varying proportions, with the presence of the two molecules being confirmed by FTIR. We studied the effect of changes in the proportion of casein, on viscosity, bio adhesiveness and mechanical properties, as this would be an important determinant of the ability of the formulation to stay in place after application. The viscosity at 37oC of the formulation increased with increasing proportion of casein: 18% (w/v) P407 with 5 and 10% casein were 1.27 and 2.84 times more viscous respectively than P407 alone. At 25% P407, addition of 10% casein increased viscosity 1.22-fold. The effect of casein addition on bio adhesion and mechanical properties was favorable to a final more adhesive topical formulation which aims spreadability, prolonged contact at site. The use of casein slowed down the drug release of bupivicaine hydrochloride (amphiphilic) and sulforhodamine B (hydrophilic) in PBS at 37oC. All the formulations were tested in rats for 6 h skin contact and none of them showed signs of irritation nor inflammation, demonstrating its potential to be tested and used in humans. Polycaprolactone nanoparticles showed a high encapsulation efficiency (98,81%) of terbinafine hydrochloride, a good polydispersity index and did not interfere in the metabolic activity of keratinocytes. They were added to the P407-casein hydrogel in different orders and concentrations. The nanoparticle's addition to the hydrogel significantly influenced gelation temperature, the viscoelastic properties and provided stable gels at the two preparation methods. Moreover, the nanoparticle addition order leads to different rheological behavior for the same nanoparticle concentration. Hydrogels driven by the addition of readily available proteins and polymeric nanoparticles have potential as translatable controlled drug release systems. The desired properties for a topical product, rheology and drug release, may be in the innovative mixture of already known components and their forms. These improvements may have an impact on patient compliance, particularly with topical therapies that may last for months and require many applications per day. However, it appears that there is still "plenty of room at the bottom" to allow continued development of drug delivery systems for decades to come (AU) | |
| FAPESP's process: | 17/10728-2 - Encapsulation and surface modulation with polycaprolactone (PCL): A novel approach for the treatment of topical fungal infections |
| Grantee: | Louise Lacalendola Tundisi |
| Support Opportunities: | Scholarships in Brazil - Doctorate |