Novel particulate antibiotic-loaded platforms as sustained drug delivery systems for bone infection treatment

Tese de doutoramento, Farmácia (Tecnologia Farmacêutica), Universidade de Lisboa, Faculdade de Farmácia, 2015

Nanofibers fabricated using triaxial electrospinning as zero order drug delivery systems

A new strategy for creating functional trilayer nanofibers through triaxial electrospinning is demonstrated. Ethyl cellulose (EC) was used as the filament-forming matrix in the outer, middle, and inner working solutions and was combined with varied contents of the model active ingredient ketoprofen (KET) in the three fluids. Triaxial electrospinning was successfully carried out to generate medicated nanofibers. The resultant nanofibers had diameters of 0.74 ± 0.06 μm, linear morphologies, smooth surfaces, and clear trilayer nanostructures. The KET concentration in each layer gradually increased from the outer to the inner layer. In vitro dissolution tests demonstrated that the nanofibers could provide linear release of KET over 20 h. The protocol reported in this study thus provides a facile approach to creating functional nanofibers with sophisticated structural features.

Synthesis of mucoadhesive thiol-bearing microgels from 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate: novel drug delivery systems for chemotherapeutic agents to the bladder

Thiol-bearing microgels have been synthesised from copolymerisation of 2-(acetylthio)ethylacrylate and 2-hydroxyethylmethacrylate, and subsequent deprotection using sodium thiomethoxide. The concentration of thiol groups on these microgels could be tailored by use of different molar ratios of the two monomers. These thiol-bearing microgels were shown to adhere to ex vivo porcine urinary bladder, which was correlated with their level of thiolation. By simply mixing solutions of thiol-bearing microgels and doxorubicin, high levels of drug loading into the microgels could be achieved. Thiol-bearing microgels controlled the release of doxorubicin in a time-dependent manner over several hours. These doxorubicin-loaded thiol-bearing microgels could have application in the treatment of early-stage bladder cancers. The method used represents a new ‘bottom-up’ approach for the synthesis of novel mucoadhesive microgels.

Nanotechnological delivery systems for the oral administration of active molecules: Polymeric microparticles and microemulsions applied to anti-inflammatory and anti-infectious drugs

This thesis was devoted to the development of innovative oral delivery systems for two different molecules. In the first part, microparticles (MPs) based on xylan and Eudragit® S- 100 were produced and used to encapsulate 5-aminosalicylic acid for colon delivery. Xylan was extracted from corn cobs and characterized in terms of its physicochemical, rheological and toxicological properties. The polymeric MPs were prepared by interfacial cross-linking polymerization and spray-drying and characterized for their morphology, mean size and distribution, thermal stability, crystallinity, entrapment efficiency and in vitro drug release. MPs with suitable physical characteristics and satisfactory yields were prepared by both methods, although the spray-dried systems showed higher thermal stability. In general, spraydried MPs would be preferable systems due to their thermal stability and absence of toxic agents used in their preparation. However, drug loading and release need to be optimized. In the second part of this thesis, oil-in-water microemulsions (O/W MEs) based on mediumchain triglycerides were formulated as drug carriers and solubility enhancers for amphotericin B (AmB). Phase diagrams were constructed using surfactant blends with hydrophiliclipophilic balance values between 9.7 and 14.4. The drug-free and drug-loaded MEs presented spherical non-aggregated droplets around 80 and 120 nm, respectively, and a low polydispersity index. The incorporation of AmB was high and depended on the volume fraction of the disperse phase. These MEs did not reduce the viability of J774.A1 macrophage-like cells for concentrations up to 25 μg/mL of AmB. Therefore, O/W MEs based on propylene glycol esters of caprylic acid may be considered as suitable delivery systems for AmB

Drug delivery systems: Past, present, and future

Drug delivery systems are essential components of drugs controlled release. In the last decades, several drug delivery technologies have emerged including capsules, liposomes. microparticles, nanoparticles, and polymers. These components must be biocompatible, biodegradable, and display a desired biodistribution providing a long-term availability of the therapeutic at specific target over time.

Nanotechnology-based Drug Delivery Systems for Dermatomycosis Treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Mucoadhesive drug delivery systems

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Magnetic multiparticulate colonic delivery systems evaluated by AC Biosusceptometry

The biomagnetic technique called Alternate Current Biosusceptometry (ACB) is a proposal to evaluate a multiparticulate drug delivery system in the human gastrointestinal tract. Results show that ACB was able to quantify the gastrointestinal transit and spreading of the magnetic material and is an attractive tool for pharmaceutical research. © 2007.

Nanotechnology-based drug delivery systems for treatment of hyperproliferative skin diseases - a review

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Nanotechnology-based drug delivery systems and herbal medicines: a review

Herbal medicines have been widely used around the world since ancient times. The advancement of phytochemical and phytopharmacological sciences has enabled elucidation of the composition and biological activities of several medicinal plant products. The effectiveness of many species of medicinal plants depends on the supply of active compounds. Most of the biologically active constituents of extracts, such as flavonoids, tannins, and terpenoids, are highly soluble in water, but have low absorption, because they are unable to cross the lipid membranes of the cells, have excessively high molecular size, or are poorly absorbed, resulting in loss of bioavailability and efficacy. Some extracts are not used clinically because of these obstacles. It has been widely proposed to combine herbal medicine with nanotechnology, because nano-structured systems might be able to potentiate the action of plant extracts, reducing the required dose and side effects, and improving activity. Nanosystems can deliver the active constituent at a sufficient concentration during the entire treatment period, directing it to the desired site of action. Conventional treatments do not meet these requirements. The purpose of this study is to review nanotechnology- based drug delivery systems and herbal medicines.

Minimum Evaporation Model of Dermatological Delivery Systems. Lamellar Liquid Crystal Formulations Containing Brazilian Nut (Bertholletia excelsa HBK) Vegetable Oil and Guarana Glycolic Extract

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Rheological, mechanical, and bioadhesive behavior of hydrogels to optimize skin delivery systems

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Skin Delivery of Kojic Acid-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Topical Application of Retinyl Palmitate-Loaded Nanotechnology-Based Drug Delivery Systems for the Treatment of Skin Aging

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Pluronics F-127/L-81 Binary Hydrogels as Drug-Delivery Systems: Influence of Physicochemical Aspects on Release Kinetics and Cytotoxicity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)