Carla M. Lopes

Directly Compressed Mini Matrix Tablets Containing Ibuprofen: Preparation and Evaluation of Sustained Release

ABSTRACT Directly compressed mini tablets were produced containing either hydroxypropylmethylcellulose (HPMC) or ethylcellulose (EC) as release controlling agent. The dynamics of water uptake and erosion degree of polymer were investigated. By changing the polymer concentration, the ibuprofen release was modified. In identical quantities, EC produced a greater sustaining release effect than HPMC. Different grades of viscosity of HPMC did not modify ibuprofen release. For EC formulations, the contribution of diffusion was predominant in the ibuprofen release process. For HPMC preparations, the drug release approached zero-order during a period of 8 h. For comparative purposes, tablets with 10 mm diameter were produced.

Overview on gastroretentive drug delivery systems for improving drug bioavailability.

In recent decades, many efforts have been made in order to improve drug bioavailability after oral administration. Gastroretentive drug delivery systems are a good example; they emerged to enhance the bioavailability and effectiveness of drugs with a narrow absorption window in the upper gastrointestinal tract and/or to promote local activity in the stomach and duodenum. Several strategies are used to increase the gastric residence time, namely bioadhesive or mucoadhesive systems, expandable systems, high-density systems, floating systems, superporous hydrogels and magnetic systems. The present review highlights some of the drugs that can benefit from gastroretentive strategies, such as the factors that influence gastric retention time and the mechanism of action of gastroretentive systems, as well as their classification into single and multiple unit systems.

Physical and Chemical Stimuli-Responsive Drug Delivery Systems: Targeted Delivery and Main Routes of Administration

In the area of drug delivery, novel tools and technological approaches have captured the attention of researchers in order to improve the performance of conventional therapeutics and patient compliance to pharmacological therapy. Stimuli-responsive drug delivery systems (DDS) appear as a promising approach to control and target drug delivery. When these DDS are administered, the drug release is activated and then modulated through some action or external input and facilitated by the energy supplied externally. The stimuli responsible to activate the drug release can be classified into three types according to their nature or the type of energy applied: physical (e.g. magnetic field, electric field, ultrasound, temperature and osmotic pressure); chemical (e.g. pH, ionic strength and glucose); and biological (enzymes and endogenous receptors). The present review gives an overview of the most significant physical and chemical stimuliresponsive DDS and elucidates about their current and relevant applications in controlled and targeted drug delivery attending different routes of administration.

E-Cadherin and β-Catenin Expression during Urothelial Carcinogenesis Induced by N-butyl-N-(4-hydroxybutyl) nitrosamine in Mice

BACKGROUND The purpose of this study was to determine the efficacy of a combination of gemcitabine and sirolimus in a mouse model of invasive bladder cancer. MATERIALS AND METHODS Gemcitabine (50 mg/kg) and sirolimus (1.5 mg/kg) were administered to animals previously exposed to N-butyl-N-4(hydroxybutyl)nitrosamine in drinking water. Tumour development was determined by histopathological evaluation. RESULTS Both drugs were well tolerated by animals. The incidence of lesions in mice treated with gemcitabine was lower in comparison to those not treated, however this result was not statistically significant. The incidence of invasive bladder cancer in animals treated with sirolimus was statistically lower (20%) than in animals not treated (54%) (p=0.008). The results indicate that this drug combination has no statistical significance on the development of pre-neoplastic urothelial lesions and had only a minor impact on invasive bladder cancer incidence in mice. CONCLUSION The combination of gemcitabine and sirolimus had only a marginal impact on invasive bladder cancer in a mouse model.BACKGROUND E-cadherin and β-catenin are adhesion molecules that promote integrity and stability of the urothelium. A decrease in their expression is associated with more aggressive tumour phenotypes with the ability to invade and metastasize. MATERIAL AND METHODS 45 ICR male mice were used, of which 25 received N-butyl-N-(4-hydroxybutyl)nitrosamine (0.05%) in drinking water for a period of 12 weeks. Immunohistochemical expression was evaluated in all urinary bladder preparations for E-cadherin and for β-catenin. RESULTS Preneoplastic lesions showed staining patterns similar to normal urothelium. In simple and nodular hyperplasia, membrane staining was dominant (66.7-78.6 and 50-100%, respectively). In dysplasia a cytoplasmic pattern was prevalent (86.7-100%). Neoplastic lesions exhibit an abnormal staining pattern (100%) with heterogeneous staining (cytoplasmic, nuclear and membrane staining). A strong correlation was observed between both adhesion molecule staining patterns (r = 0.83; p = 0.039). CONCLUSIONS In mice, as in humans, E-cadherin and β-catenin are valuable tools to investigate cellular adhesion status of urothelium and can be considered as indicators of tumour aggressiveness and evolution.

Lipid-based colloidal carriers for topical application of antiviral drugs

Abstract Herpes infections are very frequent, affecting both men and women, especially those whose immune system is weakened, and causing manifestations in face, lips, oral, nasal and genital mucosa. Herpes can also spread to other parts of the body such as the central nervous system and leave severe squeals in about 80% of cases. The current topical therapies to treat herpes infections are based on formulations containing an antiviral agent, but whose effectiveness is limited due to low skin penetration of the actives. For this reason, the development of topical formulations containing lipid-based colloidal carriers is a promising approach to promote more effective penetration through the skin and to reduce the frequency of application. This chapter provides an overview of the current lipid-based colloidal carriers developed for topical application of antiviral drugs, and summarizes the most important challenges and strategies that researchers will find when developing formulations with this purpose.

Stimuli-responsive nanosystems for drug-targeted delivery

Abstract Although scientific and technological advances have been achieved in recent decades to produce promising drug delivery systems, the continuous discovery and therapeutic needs of bioactive molecules requires a constant development of novel tools and technological approaches. Stimuli-responsive nanosystems appear as a promising strategy to control the delivery and release of encapsulated therapeutic agents, specifically at required site of action (i.e., targeting delivery). In order to design an optimized system, it is necessary to understand the different stimulus mechanisms that active the drug release, such as physical (e.g., magnetic field, electric field, ultrasound, temperature, light, radiation) or chemical (e.g., pH, redox potential enzymes, temperature). This chapter gives an overview of the most significant physical and chemical stimuli-responsive nanosystems and elucidates their current and relevant applications in controlled and targeted drug delivery attending different routes of administration.

Overview on Inhalable Nanocarriers for Respiratory Immunization

Despite the value of vaccination, the control of re-emerging infectious and non-infectious diseases remains a challenge for researchers. In this topic, mucosal immunization, in particular at airway mucosa, is receiving increased investigational focus. Innovative vaccine platforms to deliver immunogens with or without adjuvants in a safe and stable manner have been explored to improve vaccine efficacy and induce long-term and protective immunity. This review provides an overview of the features of respiratory immunization and the fate of inhalable nanocarriers in the respiratory tract. The review also highlights the most representative delivery approaches based on inhalable nanocarriers, including polymeric, lipid and inorganic-based nanosystems, which can enhance vaccine uptake by antigen-presenting cells. The review takes into consideration the most relevant and recent in vivo studies to provide readers a realistic insight into the potential of these technologies in the advantages and potential hurdles to clinical and commercial success of these platforms for vaccination.