Nanoestruturas para entrega modificada de doxiciclina: caracterização físico-química e microbiológica

Author(s)

Renata de Carvalho Feitosa

• Document type: Master's Dissertation
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Farmacêuticas
• Defense date: 2021-10-08

Examining board members

Laura de Oliveira Nascimento; Lucimara Gaziola de la Torre; Karina Cogo Müller

• Advisor: Laura de Oliveira Nascimento

Abstract

Doxycycline (DX) is a well-established antimicrobial drug that could be used to treat respiratory and buccal infections. Nonetheless, DX use is limited due to its instability in aqueous media, bacterial resistance, and low cellular penetration. It is known that the inclusion of drugs in cyclodextrin complexes or nanoparticles (NPs) can overcome these drawbacks. Thus, this study aimed to develop DX/sulfobutylether-?-Cyclodextrin (SBE-?-CD) inclusion complexes and DX-loaded chitosan nanoparticles and evaluate their physicochemical and antimicrobial properties. The formation of DX/SBE-?-CD complexes were confirmed by nuclear magnetic resonance, infrared spectroscopy, thermal analysis, X-ray diffraction and scanning electron microscopy (SEM). No improvements in DX stability in solution were observed after complex formation, however, it was identified that the complex in solid state provided increased thermal stability for the drug. DX-loaded nanoparticles were characterized by dynamic light scattering (DLS) and SEM. The applied methodology resulted in appropriate monodisperse nanoparticles (polydispersity index: 0.039, particle size: 209.7 nm, zeta potential: 17.5 mV) with sufficient encapsulation rate (25.2%) to be evaluated in microbiological studies. Both formulations (NPs and complex) maintained the antimicrobial activity of DX against Staphylococcus aureus, while only the DX/SBE-?-CD inclusion complexes were active against Klebsiella pneumoniae. We believe that NPDX has not shown action against K. pneumoniae due to the concentration tested being close to the limit of minimum inhibitory concentration, however, it is possible to solve this issue through lyophilization of NPs, which would allow increased concentration. Thus, the formulations obtained are able to protect the drug thermally and have the potential to be used as drug delivery systems for the treatment of local infections (AU)

• FAPESP's process: 19/08281-5 - Development of biopolymeric wafers for buccal delivery of nanostructured drugs
• Grantee: Renata de Carvalho Feitosa
• Support Opportunities: Scholarships in Brazil - Master