Microemulsões: Estrutura e aplicações como sistema de liberação de fármacos

Depending on formula composition, microemulsions may be used as a vehicle for drug administration. In this work the main applicable parameters used in the development of pharmaceutical microemulsions (ME) are analyzed. The conceptual description of the system, theoretical parameters related to formation of internal phases and some aspects of ME stability are described. The pseudo ternary phase diagram is used to characterize ME boundaries and to describe different structures in several regions of the diagram. Some applications of ME as drug delivery systems for different administration routes are also analyzed. ME offer advantages as drug delivery systems, because they favor drug absorption, being in most cases faster and more efficient than other methods in delivering the same amount of drug.

Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: Comparative effects of helium and nitrogen

Background: Lung deposition of intravenous cephalosporins is low. The lung deposition of equivalent doses of ceftazidime administered either intravenously or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as the carrying gas of the aerosol was compared in ventilated piglets with and without experimental bronchopneumonia. Methods: Five piglets with noninfected lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg ceftazidime by ultrasonic nebulization. In each group, the ventilator was operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen mixture. Animals were killed, and multiple lung specimens were sampled for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography. Results: As compared with intravenous administration, nebulization of ceftazidime significantly increased lung tissue concentrations (17 ± 13 vs. 383 ± 84 μg/g in noninfected piglets and 10 ± 3 vs. 129 ± 108 μg/g in piglets with experimental bronchopneumonia; P < 0.001). The use of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung tissue concentrations in noninfected piglets (576 ± 141 μg/g; P < 0.001) and no significant change in infected piglets (111 ± 104 μg/g). Conclusion: Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentrations as compared with intravenous administration. Using a helium-oxygen mixture as the carrying gas of the aerosol induced a substantial additional increase in lung deposition in noninfected piglets but not in piglets with experimental bronchopneumonia. © 2005 American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.

Estudos sobre liberação controlada e vetorização de drogas através de lipossomas

The text highlights the state of research related with the application of liposomes in the control of drug delivery and drug target to infectious diseases. Liposomes have several pharmaceutical applications and this manuscript is primarily focused on the potential of this colloidal system as an antibiotic carrier system and of administration through several accesses via to organism. Numerous case studies in which liposomes have successfully been used to improve pharmacological drug effect are presented. Mechanisms involved in drug delivery, application possibilities, research and development and efforts to reach these objectives are discussed. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

Advances in prodrug design

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given. © 2005 Bentham Science Publishers Ltd.

Ftalato de di-(2-etilexila) (DEHP) em bolsas de PVC para soluções parenterais de grandes volumes

Large volume parenteral solutions (LVPS) are widely used as vehicles for intravenous administration of drugs and polyvinyl chloride (PVC) flexible bags are, nowadays, the plastic containers most commonly used to pack and drip-feed LVPS. An advantage of using bags is that they collapse flat and thus reduce the risk of airborne contamination and embolism caused by air in the bloodstream. They are mainly used in hospitals. This review deals with some important aspects of the PVC packaging containing the plasticizer DEHP, generally used to pack LVPS. The interaction between drug and package is discussed, with an emphasis on the migration of DEHP from the PVC bag to LVPS containing the immunosuppressant cyclosporin, and toxicological aspects are considered.

Ethylcelullose microspheres containing sodium diclofenac: Development and characterization

The objective of the present study was the development and characterization of ethylcellulose microspheres containing diclofenac and the determination of the in vitro drug release profile. Microspheres were prepared by emulsification/solvent evaporation method using ethyl acetate as solvent for the polymer and water as non solvent. The microspheres were characterized by morphologic and granulometric analyses. The amount of encapsulated drug as well as its release profile in vitro were also determined. The product obtained was microparticles with smooth surface and narrow size distribution, about 50% of the particles being smaller than 5 μm. The methodology used allowed drug encapsulation with a good yield and the system provided a controlled release of diclofenac.

Thermoanalytical study of praziquantel-loaded PLGA nanoparticles

Polymeric nanoparticles have received great attention as potential controlled drug delivery systems. Biodegradable polymers has been extensively used in the development of these drug carriers, and the polyesters such as polylactic acid, polyglycolic acid and their copolymers as poly-lactide-co- glycolide are the most used, considering its biocompatibility and biodegradability. Thermal analysis techniques have been used for pharmaceutical substances for more than 30 years and are routine methods for screening drug-excipient interactions. The aim of this work is to use thermal analysis to characterize PLGA nanoparticles containing a hydrophobic drug, praziquantel. The results show that the drug is in an amorphous state or in disordered crystalline phase of molecular dispersion in the PLGA polymeric matrix and that the microencapsulation process did not interfere with the chemical structure of the polymer, mantaining the structural drug integrity.

Estratégias biotecnológicas para a liberação controlada de antígenos e adjuvantes em vacinas através de lipossomas

Liposomes (LP) are colloidal systems with ability to compartmentalize therapeutic molecules in order to improve biological activity, decreases the potential toxicity, and to obtain prolonged effect. In this work it was discussed the role of the various liposomes types to encapsulate drug molecules able to provoke some immunological response (drugs, antigens and DNA). The effect of the liposomes and the parameters about the formation of the structures are also analyzed. Detailed literature review shows that, depending on the molecules polarity and the superficial charge of the liposome structures, the system may be efficiently used to optimize the therapeutic effects by means of the release control or through a drug delivery mechanism.

Preparação e caracterização inicial de complexo de inclusão entre nitrofurazona e 2-hidroxipropil-β-ciclodextrina

Nitrofurazone (NF), 5-nitro-2-furaldehyde semicarbazone, a broad-spectrum antibiotic, has reported toxic effects and low solubility in water. It would be of great interest to form inclusion complexes between NF and a cyclodextrin, to develop more effective and safer antibiotic formulations. This paper focuses on the preparation of inclusion complexes of NF with 2-hydroxypropyl-β- cyclodextrin (HP-β-CD) and their initial characterization by evaluating rates of complex formation, photostability, solubility isotherms, release rate profiles, stoichiometry of the complexes and their morphology, as revealed by scanning electron microscopy. The kinetic tests of complex formation revealed that 17,3 h is enough for stabilization of the NF-cyclodextrin complex. The solubility isotherm studies showed that the isotherm changes from type A to type B, as a function of temperature. The photostability experiments showed that the insertion of the NF in the HP-β-CD cavity protects the drug from photodecomposition. The release kinetic tests showed that the profile of NF release from the complex is altered by the presence of HP-β-CD in the medium. A Job's plot indicated that the stoichiometry of the complex was 1:1 NF:HP-β-CD. The scanning electron micrographs showed changes in the crystal structure of NF in the complex. This study focused on the physicochemical properties of drug-delivery formulations that could potentially be developed into a novel type of therapy with NF.

Sistemas biodegradáveis contendo acetato de prednisolona para administração orbitária

Purpose: The present study aimed to evaluate an injectable extended-release formulation of prednisolone acetate (PA) for orbital administration. Methods: Microspheres (MEs) of poly-ε-caprolactone (PCL) containing PA were developed by the method of solvent evaporation. The MEs obtained were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), encapsulation efficiency and in vitro release profile. The in vivo release profile was evaluated in rabbits after periocular injection of an aqueous suspension of MEs. The local biocompatibility of the system was verified by histopathologic analysis of the deployment region. Results: After MEs preparation, morphological analysis by SEM showed the feasibility of the employed method. The content of PA encapsulated was 43 ± 7% and can be considered as satisfactory. The system characterization by DSC technique, in addition to confirm the system stability, did not indicate the existence of interaction between the drug and the polymer. The in vitro release study showed the prolonged-release features of the developed system. Preliminary in vivo study showed the absence of local toxicity and confirmed the prolonged release profile of PA from MEs, suggesting the viability of the developed system for the treatment of orbital inflammatory diseases. Conclusion: The results obtained in this work are relevant and accredit the system developed as a possible alternative to the treatment of inflammatory orbitopathy.

Estudo de perfil de dissolução dos medicamentos de referência, genérico e similar contendo cefalexina na forma farmacêutica cápsula

With recent advances in technology and research into drug delivery, the modernization of tests and greater emphasis on the predictability of therapeutic effect by means of in vitro tests, the dissolution test and the study of dissolution profiles are gaining more and more importance. Though introduced initially as a way of characterizing the release profile of poorly soluble drugs, dissolution tests are currently part of pharmacopoeial monographs on almost all the oral solid pharmaceutical forms. The objective of this study was to determine the dissolution profile (percent drug dissolved versus time) of the pioneer brand, generic and similar pharmaceutical capsules containing 500mg cephalexin. Three pharmaceutical brands (reference, generic and similar) were subjected to the dissolution test and in vitro dissolution profiles were recorded. From the results of the dissolution test, it was concluded that the samples met the acceptance criterion, as no difference was observed in the percentage of the drug dissolved in a standard time. The dissolution profile indicated that this medicine, in this pharmaceutical form, dissolves readily (85% of the drug dissolved in 15 minutes) and the curves showed great similarity, suggesting that the 3 brands are pharmaceutically equivalent.

Biocompatible microemulsion modifies the pharmacokinetic profile and cardiotoxicity of doxorubicin

Doxorubicin (DOX) is an anthracycline antibiotic with a broad antitumor spectrum. However, the clinical use of DOX is limited because of its cardiotoxicity, a dose-dependent effect. Colloidal drug delivery systems, such as microemulsions (MEs), allow the incorporation of drugs, modifying the pharmacokinetic (PK) profile and toxic effects. In this study, we evaluated the PK profile and cardiotoxicity of a new DOX ME (DOX-ME). The PK profile of DOX-ME was determined and compared with that of the conventional DOX after single-dose administration (6mg/kg, intravenous) in male Wistar rats (n = 12 per group). The cardiotoxicity of DOX formulations was evaluated by serum creatine kinase MB (CKMB) activity in both animal groups before and after drug administration. The plasma DOX measurements were performed by high-performance liquid chromatography with fluorescence detection, and the CKMB levels were assayed using the CKMB Labtest® kit. The ME system showed a significant increase in plasma DOX concentrations and lower distribution volume when compared with conventional DOX. Serum CKMB activity increased after conventional DOX administration but was unchanged in the DOX-ME group. These results demonstrate modifications in drug access to susceptible sites using DOX-ME. DOX-ME displayed features that make it a promising system for future therapeutic application. © 2012 Wiley Periodicals, Inc.

Ureasil-polyether hybrid film-forming materials

The objectives of this work were to study the suitability and highlight the advantages of the use of cross-linked ureasil-polyether hybrid matrices as film-forming systems. The results revealed that ureasil-polyethers are excellent film-forming systems due to specific properties, such as their biocompatibility, their cosmetic attractiveness for being able to form thin and transparent films, their short drying time to form films and their excellent bioadhesion compared to the commercial products known as strong adhesives. Rheological measurements have demonstrated the ability of these hybrid matrices to form a film in only a few seconds and Water Vapor Transmitting Rate (WVTR) showed adequate semi-occlusive properties suggesting that these films could be used as skin and wound protectors. Both the high skin bioadhesion and non-cytotoxic character seems to be improved by the presence of multiple amine groups in the hybrid molecules. © 2012 Elsevier B.V.

Photodynamic inactivation of planktonic cultures and biofilms of Candida albicans mediated by aluminum-chloride-phthalocyanine entrapped in nanoemulsions

New drug delivery systems, such as nanoemulsions (NE), have been developed to allow the use of hydrophobic drugs on the antimicrobial photodynamic therapy. This study evaluated the photodynamic potential of aluminum-chloride- phthalocyanine (ClAlPc) entrapped in cationic and anionic NE to inactivate Candida albicans planktonic cultures and biofilm compared with free ClAlPc. Fungal suspensions were treated with different delivery systems containing ClAlPc and light emitting diode. For planktonic suspensions, colonies were counted and cell metabolism was evaluated by XTT assay. Flow cytometry evaluated cell membrane damage. For biofilms, the metabolic activity was evaluated by XTT and ClAlPc distribution through biofilms was analyzed by confocal laser scanning microscopy (CLSM). Fungal viability was dependent on the delivery system, superficial charge and light dose. Free ClAlPc caused photokilling of the yeast when combined with 100 J cm-2. Cationic NE-ClAlPc reduced significantly both colony counts and cell metabolism (P < 0.05). In addition, cationic NE-ClAlPc and free ClAlPc caused significant damage to the cell membrane (P < 0.05). For the biofilms, cationic NE-ClAlPc reduced cell metabolism by 70%. Anionic NE-ClAlPc did not present antifungal activity. CLSM showed different accumulation on biofilms between the delivery systems. Although NE system showed a lower activity for planktonic culture, cationic NE-ClAlPc showed better results for Candida biofilms. Candida albicans biofilm overview after 30 min of contact with free ClAlPc. This study presents the photodynamic potential of aluminum-chloride-phthalocyanine (ClAlPc) entrapped in cationic and anionic nanoemulsions (NE) to inactivate C. albicans planktonic cultures and biofilm comparing with free ClAlPc. The photodynamic effect was dependent on the delivery system, superficial charge and light dose. Cationic NE-ClAlPc and free ClAlPc caused significant reduction in colony counts, cell metabolism and damage to the cell membrane (P < 0.05). However, only the free ClAlPc was able to cause photokilling of the yeast. The anionic NE-ClAlPc did not present antifungal activity. Although NE system showed a lower activity for planktonic culture, cationic NE-ClAlPc showed better results for Candida biofilms. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

Blends of cross-linked high amylose starch/pectin loaded with diclofenac

Polymers blends represent an important approach to obtain materials with modulated properties to reach different and desired properties in designing drug delivery systems in order to fulfill therapeutic needs. The aim of this work was to evaluate the influence of drug loading and polymer ratio on the physicochemical properties of microparticles of cross-linked high amylose starch-pectin blends loaded with diclofenac for further application in controlled drug delivery systems. Thermal analysis and X-ray diffractograms evidenced the occurrence of drug-polymer interactions and the former pointed also to an increase in thermal stability due to drug loading. The rheological properties demonstrated that drug loading resulted in formation of weaker gels while the increase of pectin ratio contributes to origin stronger structures. © 2012 Elsevier Ltd.