Evaluation of methotrexate-loaded surfactants, ceramides and cholesterol-based lamellar phases as a topical treatment for psoriasis.

OBJECTIVE: Psoriasis is a chronic inflammatory skin disorder. Oral or subcutaneous methotrexate (MTX) is a first-line antipsoriatic treatment, whose adverse effects can be observed even at low doses. To minimize systemic side effects, antipsoriatic drugs should be administered topically, since they could permeate the stratum corneum. As liquid crystals with lamellar phase (LP) can be helpful in promoting skin permeation, this work evaluated two MTX-loaded LPs (C1CH and C1CHCE), based on stearic acid, cholesterol and ceramides, like topical treatments for mice with imiquimod-induced psoriasis. METHODS: C1CH and C1CHCE were topically administered to mice with imiquimod-induced psoriasis. Dexamethasone cream was used as positive treatment control. Skin histology and inflammation biomarkers were assessed. KEY FINDINGS: C1CH and C1CHCE exhibited marked immunomodulatory effects and induced extensive microstructural skin remodelling on the epidermis and dermis. These formulations increased keratinization score, epidermis thickness, inflammatory infiltrate, hair follicle hypertrophy and vascular congestion in the dermis. C1CH and C1CHCE also attenuated IL-10 upregulation and upregulated IL-1, IFN-γ, TNF-α and prostaglandin E2 levels, as well as myeloperoxidase, N-acetyl-ß-d-glucosaminidase and cyclooxygenase 2 activity compared with untreated psoriatic animals. CONCLUSION: Although liquid crystals have been reported as good options for carrying topical drugs, they need to be carefully assessed on a case-by-case basis.

Influence of the ionic strength on the physicochemical properties of methotrexate-loaded chitosan polyelectrolyte complexes

Abstract Polyelectrolyte complexes (PECs) as drug delivery systems are widely explored since they are easily obtained by coacervation and biopolymers can be associated. However, particle distribution is a challenging critical parameter that has been infrequently focused. This work evaluated the effect of NaCl concentration on the physicochemical properties of PECs based on chitosan and hypromellose loaded with methotrexate. The particle size, zeta potential and polydispersity index (PdI) were determined by DLS, besides of drug entrapment efficiency (EE) and in vitro drug release profile determination. Particle size decreased while NaCl concentration rised, achieving a narrower size distribution of (345±79 nm) and PdI (0.285±0.067) with 200 mmol/L NaCl. The higher the NaCl concentration, the lower the zeta potential at acid pH. The EE was kept similar ((28.2±4.5) %) from 0 to 300 mmol/L NaCl, while 400 mmol/L NaCl impaired the drug entrapment. The addition of (200 and 300) mmol/L NaCl did not affect the drug release profile, but it was faster with (100 or 400) mmol/L. In conclusion, the addition of 200 mmol/L NaCl reduced particle size and PdI with no changes in the EE and drug release. Therefore, the ionic strength plays an important role on PECs development.

Preclinical Evaluation of Polymeric Nanocomposite Containing Pregabalin for Sustained Release as Potential Therapy for Neuropathic Pain.

This study offers a novel oral pregabalin (PG)-loaded drug delivery system based on chitosan and hypromellose phthalate-based polymeric nanocomposite in order to treat neuropathic pain (PG-PN). PG-PN has a particle size of 432 ± 20 nm, a polydispersity index of 0.238 ± 0.001, a zeta potential of +19.0 ± 0.9 mV, a pH of 5.7 ± 0.06, and a spherical shape. Thermal and infrared spectroscopy confirmed nanocomposite generation. PG-PN pharmacokinetics was studied after a single oral dose in male Wistar rats. PG-PN showed greater distribution and clearance than free PG. The antinociceptive effect of PG-PN in neuropathic pain rats was tested by using the chronic constriction injury model. The parameter investigated was the mechanical nociceptive threshold measured by the von Frey filaments test; PG-PN showed a longer antinociceptive effect than free PG. The rota-rod and barbiturate sleep induction procedures were used to determine adverse effects; the criteria included motor deficit and sedative effects. PG-PN and free PG had plenty of motors. PG-PN exhibited a less sedative effect than free PG. By prolonging the antinociceptive effect and decreasing the unfavorable effects, polymeric nanocomposites with pregabalin have shown promise in treating neuropathic pain.

Preclinical study of methotrexate-based hydrogels versus surfactant based liquid crystal systems on psoriasis treatment.

Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies.

The liquid crystalline phase behaviour of a nasal formulation modifies the brain disposition of donepezil in rats in the treatment of Alzheimer's disease.

Although nanoparticles, polymeric micelles, liposomes, nanoemulsions, and microemulsions were extensively evaluated as formulations for nasal administration of drugs, lyotropic liquid crystal (LLC) mesophases have been few studied. The phase transition from a low-viscosity microemulsion to a more viscous LLC may improve the mucoadhesion of the formulation. Donepezil is a drug administered orally in the treatment of Alzheimer's disease, and with gastrointestinal side effects that are typical of acetylcholinesterase inhibitors. Based on this, donepezil administration by nasal pathway using a mucoadhesive LLC may be a feasible alternative. A colloidal formulation was selected from a ternary diagram, combining CETETH-10, oleic acid, and water (40:45:15, w/w). Donepezil was incorporated into the formulation, and the characterisation included in vitro studies, such as mucoadhesion and drug release. Pharmacokinetics in Wistar rats included evaluations by the nasal pathway with donepezil incorporated into microemulsion. A phase transition from an isotropic to an anisotropic system was observed after the swelling of the microemulsion with artificial nasal fluid (12-20 %). The release of donepezil in vitro occurred in a sustained manner. Significant levels of donepezil were achieved in the brain after nasal administration of the microemulsion, as a promising strategy for the treatment of Alzheimer's disease.

Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis.

This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 ± 166 nm particle size, 0.298 ± 0.108 polydispersity index, +26 ± 2 mV and 74.3 ± 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7°C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1ß level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug.

Mucoadhesive nanostructured lipid carriers as a cannabidiol nasal delivery system for the treatment of neuropathic pain.

The therapeutic potential of cannabidiol (CBD) has been explored to treat several pathologies, including those in which pain is prevalent. However, the oral bioavailability of CBD is low owing to its high lipophilicity and extensive first-pass metabolism. Considering the ability of the nasal route to prevent liver metabolism and increase brain bioavailability, we developed nanostructured lipid carriers (NLCs) for the nasal administration of CBD. We prepared particles with a positively charged surface, employing stearic acid, oleic acid, Span 20Ⓡ, and cetylpyridinium chloride to obtain mucoadhesive formulations. Characterisation of the CBD-NLC dispersions showed uniform nano-sized particles with diameters smaller than 200 nm, and high drug encapsulation. The mucoadhesion of cationic particles has been related to interactions with negatively charged mucin. Next, we added in-situ gelling polymers to the CBD-NLC dispersion to obtain a CBD-NLC-gel. A thermo-reversible in-situ forming gel was prepared by the addition of PluronicsⓇ. CBD-NLC-gel was characterised by its gelation temperature, rheological behaviour, and mucoadhesion. Both formulations, CBD-NLC and CBD-NLC-gel, showed high mucoadhesion, as assessed by the flow-through method and similar in vitro drug release profiles. The in vivo evaluation showed that CBD-NLC dispersion (without gel), administered intranasally, produced a more significant and lasting antinociceptive effect in animals with neuropathic pain than the oral or nasal administration of CBD solution. However, the nasal administration of CBD-NLC-gel did not lessen mechanical allodynia. These findings demonstrate that in-situ gelling hydrogels are not suitable vehicles for highly lipophilic drugs such as CBD, while cationic CBD-NLC dispersions are promising formulations for the nasal administration of CBD.

Determination of dexamethasone acetate in CETETH 20-based in liquid crystalline systems using HPLC.

Dexamethasone acetate (DEX), a potent anti-inflammatory, is used primarily in the treatment of inflammatory and autoimmune diseases. It was incorporated in CETETH 20 (polyoxyethylene 20 cetyl alcohol)-based liquid crystalline systems to enhance the purpose of the drug. Concomitant with the pharmaceutical technology performed, a HPLC method was developed and validated for the quantification of dexamethasone acetate in CETETH 20-based liquid crystalline systems for the evaluation of the drug in the new matrix. The method was performed using a C18 column with acetonitrile:methanol:water (35:35:30, v/v/v) as the mobile phase at a flow rate of 0.8 mL min-1 at 239 nm. The method was linear in the range of 1-25 µg mL-1 ; the limit of quantification and limit of detection were 0.05 and 0.16 µg mL-1 , respectively; the accuracy of the method was 99.92% (relative standard deviation < 1%), and it presented intra-day and inter-day precision with deviations less than 1%. In this context, the method was successfully used to determine the incorporation efficiency of DEX in CETETH 20-based liquid crystalline systems and can be easily used by pharmaceutical companies and laboratories around the world.

Evaluation of polyelectrolyte and emulsion covalent crosslink of chitosan for producing mesalasine loaded submicron particles

This study evaluates various techniques for producing mesalamine (5ASA)-loaded particles employing chitosan as a biopolymer: (1) the polyelectrolyte complexation of chitosan with phthalate hypromelose (HP), (2) the chemical crosslinking of chitosan with genipin and (3) the water-in-oil emulsion method associated with chemical crosslinking with genipin. Systems were characterized by dynamic light scattering, zeta potential (ζ), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and a drug release profile. Method (1) was efficiently produced unloaded nanoparticles (491 nm, PdI=0.26 and ζ = 23.2), but the conditions for chitosan and HP cross-linking enhanced the precipitation of 5ASA. Method (2) caused the degradation of the drug. Method 3 produced sub-micron and microparticles, thereby varying the agitation method; 3 h magnetic agitation resulted in 2692 nm, Pdi = 0.6 and ζ = 46, while Ultra-Turrax, 5 min produced submicron particles (537 nm, PdI = 0.6). The percentage yield was approximately 50%, which is very satisfactory considering the impossibility of encapsulating 5ASA using other methods. FTIR showed the covalent interaction of chitosan and genipin. The drug release was rapid in acidic fluid, but in neutral pH a slower release was obtained in the initial stage, followed by rapid release, which may ensure the controlled release of 5ASA in the colon.

Computational and experimental approaches for development of methotrexate nanosuspensions by bottom-up nanoprecipitation.

Development of nanosuspensions offers a promising tool for formulations involving poorly water-soluble drugs. In this study, methotrexate (MTX) nanosuspensions were prepared using a bottom-up process based on acid-base neutralization reactions. Computational studies were performed to determine structural and electronic properties for isolated molecules and molecular clusters in order to evaluate the mechanism of MTX nanoparticle formation. Computational results indicated that the clusters in zwitterionic and cationic states presented larger dimensions and higher energies of interaction between MTX molecules, which favored aggregation. In contrast, the clusters in the anionic state exhibited lower energies of interaction, indicating aggregation was less likely to occur. Experimental results indicated that the higher the HCl proportion during drug precipitation, the greater the particle size, resulting in micrometric particles (2874-7308nm) (cationic and zwitterionic forms). However, MTX nanoparticles ranging in size from 132 to 186nm were formed using the lowest HCl proportion during drug precipitation (anionic form). In vitro release profiles indicated that the drug release rate from nanosuspension was increased (approximately 2.6 times) over that of the raw material. Overall, computational modeling and experimental analysis were complementary and assisted in the rational design of the nanosuspension based on acid-base reactions.

Molecularly imprinted microparticles in lipid-based formulations for sustained release of donepezil.

Donepezil is a drug administered for Alzheimer's disease treatment, and it is a potential template molecule for imprinted microparticles. The precipitation polymerization technique allows the synthesis of spherical imprinted microparticles, and the intermolecular interactions among drug and molecularly imprinted polymers (MIPs) play a promising role for delineating drug delivery systems. Once that donepezil is a poorly-water soluble compound, lipid based-formulations (LBFs) may enhance its oral administration. Based on this, LBFs are useful vehicles to incorporate imprinted microparticles synthesized by precipitation polymerization. In these formulations, the drug dissolved in lipids is accessible to adsorbate in the polymers, and the hydrophobic environment of lipids increases the molecular recognition of MIPs. The formulations based on MIPs using pure oleic acid as vehicle prolong the in vitro release of donepezil up to several hours by a Fickian diffusion mechanism, and it provides a multiphasic release pattern related to the heterogeneity of the binding sites. The modulation of donepezil release from MIPs-based formulations using oil vehicles may contribute to decrease its side effects, possibly regulating its absorption rate in the gastrointestinal tract. These systems represent a novel technological platform to prolong the delivery not only for donepezil, but also for a variety of therapeutics.

Exploring the Phase Behavior of Monoolein/Oleic Acid/Water Systems for Enhanced Donezepil Administration for Alzheimer Disease Treatment.

Donepezil is a drug usually administered by oral route for Alzheimer disease treatment, but several gastric side effects have been reported as diarrhea, nausea, and anorexia. We explored the phase behavior of lyotropic liquid crystalline (LLC) mesophases composed by monoolein/oleic acid/water for enhanced administration of donepezil. Polarized light microscopy suggested that these systems ranged from isotropic inverse micellar solutions (L2) to viscous and birefringent reverse hexagonal (HII) mesophases according to the amount of water in the ternary systems. Phase transition was observed from a L2 phase to HII mesophase after swelling studies, an interesting property to be explored as a precursor of LLC mesophases for mucosal administration that increases its viscosity in situ. Mucoadhesive properties of LLC mesophases were characterized using a texture analyzer indicating that these systems can have an increased residence time in the site of absorption. Donepezil-free base was incorporated in the evaluated formulations, and their in vitro release was controlled up to 24 h. The phase behavior of the systems demonstrated a great potential for enhanced donepezil administration once these mucoadhesive-controlled release formulations can incorporate the drug and prolong its release, possibly reducing its side effects.

Design and Characterization of Silicone and Surfactant Based Systems for Topical Drug Delivery.

Nanotechnology offers advantages for new drug delivery design by providing drug targeting while minimizing the side effects. Polyoxyethylene 20 cetyl alcohol (CETETH-20) is a surfactant that may form nanostructured systems, such as liquid crystals, when in contact with water/oil, which are structurally similar to biological membranes and may improve skin interaction. The aim of this study was to develop and characterize CETETH 20-based nanostructured systems by combining CETETH-20 with water and different oily phases, including PEG-12-dimethicone for topical drug administration. The systems were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheology, texture profile analyses (TPA), in vitro cytotoxicity and histopathological analyses of rabbits' skin. Lamellar, hexagonal and cubic phases were identified and their viscoelastic moduli varied according to each phase. The stiffness of the cubic phase was 3-fold higher and twice more adhesive than the hexagonal phase. The formulations did not affect the normal macrophages cells, neither promoted skin irritation. They were spontaneously obtained by simply mixing the components, which corroborates for an ease scaled-up. These results suggest that systems composed of CETETH 20, PEG-12-dimethicone and water are a promising new approach for designing nanostructured topical drug delivery systems.

Preparation and Characterization of Chitosan Nanoparticles for Zidovudine Nasal Delivery.

Zidovudine (AZT) is the antiretroviral drug most frequently used for the treatment of Acquired Immunodeficiency Syndrome. Its low oral bioavailability demands the development of innovative strategies to overcome the first pass metabolism. The nasal route is an option for enhanced therapeutic efficacy and to reduce the extent of the first-pass effect. In this article, AZT loaded chitosan nanoparticles were prepared by a modified ionotropic gelation method with sodium tripolyphosphate. The increase proportion of CS (NP1 10:01 (w/w)) promoted the formation of smaller nanoparticles (260 nm), while raising the proportion of TPP (NP2 5:1 w/w) increased the nanoparticles size (330 nm). The incorporation of AZT increased the nanoparticles size for both AZT-loaded nanoparticles AZT-loaded NP1 (406 nm) and AZT-loaded NP2 (425 nm). The incorporation of AZT into NP1 did not change the electrophoretic mobility, however, in AZT-loaded NP2 there was a significant increase. The positive surface of the nanoparticles is very important for the mucoadhesive properties due interaction with the sialic groups of the mucin. Nuclear resonance magnetic data showed that the higher concentration of chitosan in the nanoparticles favored the interaction of few phosphate units (pyrophosphate) by ionic interaction Scanning electron microscopy, revealed that the nanoparticles are nearly spherical shape with porous surface. The entrapment efficiency of AZT, was 17.58% ± 1.48 and 11.02% ± 2.05 for NP1 and NP2, respectively. The measurement of the mucoadhesion force using mucin discs and nasal tissue obtained values of NP1 = 2.12 and NP2 = 4.62. In vitro permeation study showed that the nanoparticles promoted an increase in the flux of the drug through the nasal mucosa. In view of these results, chitosan nanoparticles were found to be a promising approach for the incorporation of hydrophilic drugs and these results suggest that the CS-containing nanoparticles have great potential for nasal AZT administration.

Nasal administration of liquid crystal precursor mucoadhesive vehicle as an alternative antiretroviral therapy.

The purpose of this study was to develop a mucoadhesive stimuli-sensitive drug delivery system for nasal administration of zidovudine (AZT). The system was prepared by formulating a low viscosity precursor of a liquid crystal phase, taking advantage of its lyotropic phase behavior. Flow rheology measurements showed that the formulation composed of PPG-5-CETETH-20, oleic acid and water (55, 30, 15% w/w), denominated P, has Newtonian flow behavior. Polarized light microscopy (PLM) revealed that formulation P is isotropic, whereas its 1:1 (w/w) dilution with artificial nasal mucus (ANM) changed the system to an anisotropic lamellar phase (PD). Oscillatory frequency sweep analysis showed that PD has a high storage modulus (G') at nasal temperatures. Measurement of the mucoadhesive force against excised porcine nasal mucosa or a mucin disk proved that the transition to the lamellar phase tripled the work of mucoadhesion. Ex vivo permeation studies across porcine nasal mucosa exhibited an 18-fold rise in the permeability of AZT from the formulation. The Weibull mathematical model suggested that the AZT is released by Fickian diffusion mechanisms. Hence, the physicochemical characterization, combined with ex vivo studies, revealed that the PPG-5-CETETH-20, oleic acid, and water formulation could form a mucoadhesive matrix in contact with nasal mucus that promoted nasal absorption of the AZT. For an in vivo assessment, the plasma concentrations of AZT in rats were determined by HPLC method following intravenous and intranasal administration of AZT-loaded P formulation (PA) and AZT solution, respectively, at a dose of 8mg/kg. The intranasal administration of PA resulted in a fast absorption process (Tmax=6.7min). Therefore, a liquid crystal precursor formulation administered by the nasal route might represent a promising novel tool for the systemic delivery of AZT and other antiretroviral drugs. In the present study, the uptake of AZT absorption in the nasal mucosa was demonstrated, providing new foundations for clinical trials in patients with AIDS.

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

BACKGROUND: Hydrogels are widely used for cutaneous formulations; thereby comparing the bioadhesive properties of polymers with a view to prolong the residence time of topical drugs on the skin would be very useful to design novel topical drug delivery systems. AIM: The objective of this study was to correlate data from rheological studies and texture profile analysis, with bioadhesion on the skin. METHODS: Polyacrylic acid polymers used were carbomer homopolymer type A (C971) and type B (C974), and polycarbophil (PP) dispersed in water at various concentrations (0.1, 0.5, 1.0, 1.5, 2.0, 3.0, 5.0%, w/v). Rheological, texture, and bioadhesive properties were determined to compare the hydrogels. RESULTS: Rheological analysis showed that all samples exhibited pseudoplastic behavior with thixotropy. Texture profile analysis showed that compressibility, hardness, and adhesiveness of the hydrogels were dependent on the polymer concentration, and the cohesion values were high. Bioadhesion of C974 and PP at 0.5 and 2% was of the same magnitude, while all samples of C971 had lower values. The bioadhesion of 5% C974 was the highest, while that 5% PP was lower, possibly because PP showed the greatest hardness and this rigidity may decrease the interaction of the polymer with the skin. CONCLUSION: A comprehensive comparative rheological and textural analyses of several polymers for topical systems were undertaken in terms of their bioadhesion. Therefore, it is possible to conclude that these polymers can be used for optimization of drug delivery systems on the skin.

Rheological, mechanical and adhesive properties of surfactant-containing systems designed as a potential platform for topical drug delivery.

In the last few decades, nanotechnology has led to an advance in the development of topical drug delivery. Nanostructured drug delivery systems enable the compartmentalization of drugs in restricted environments, modifying the release profile and maintaining the required drug concentration for prolonged periods at the site of action and/or absorption. The development of nanostructured systems containing surfactants has evolved rapidly. Mixtures of surfactant, oil and water can self-associate to form structures, such as microemulsions and liquid crystal phases, which can be exploited as drug delivery systems because their nanostructured organization can control drug release. Therefore, the purpose of this study was to assess the potential of systems containing polyoxypropylene (5) polyoxyethylene (20) cetyl ether as surfactant, oleic acid or mineral oil as the oily phase, and water to be used as a platform in the development of topical drug delivery systems. Physicochemical characterization of the systems was performed by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological tests and texture profile analysis. The ternary phase diagrams showed that combinations of surfactant/mineral oil/water and surfactant/oleic acid/water could form various thermodynamically stable structures, such as microemulsions and liquid crystals. The oily phases, oleic acid and mineral oil, changed the rheological, mechanical and adhesive properties of systems containing polyoxypropylene (5) polyoxyethylene (20) cetyl ether.

Mucoadhesive drug delivery systems / Sistemas de entrega de drogas mucoadesiva

Drug actions can be improved by developing new drug delivery systems, such as the mucoadhesive system. These systems remain in close contact with the absorption tissue, the mucous membrane, releasing the drug at the action site leading to a bioavailability increase and both local and systemic effects. Mucoadhesion is currently explained by six theories: electronic, adsorption, wettability, diffusion, fracture and mechanical. Several in vitro and in vivo methodologies are proposed for studying its mechanisms. However, mucoadhesion is not yet well understood. The aim of this study was to review the mechanisms and theories involved in mucoadhesion, as well as to describe the most-used methodologies and polymers in mucoadhesive drug delivery systems.

O efeito de fármacos pode ser potencializado através do desenvolvimento de novos sistemas de liberação como os sistemas mucoadesivos. Estes sistemas permanecem em contato íntimo com o tecido de absorção, as mucosas, liberando o fármaco no local de ação, com o consequente aumento da biodisponibilidade, podendo promover efeitos locais e sistêmicos. A mucoadesão, atualmente, é explicada por seis teorias, a eletrônica, da adsorção, da molhabilidade, da difusão, da fratura e a mecânica. Para estudar seus mecanismos e quantificá-la, são propostas várias metodologias in vitro e in vivo. Porém, a mucoadesão ainda não é totalmente compreendida. Esse trabalho tem por objetivo revisar os mecanismos e as teorias envolvidas na mucoadesão, além de descrever as metodologias e os polímeros mais utilizados em sistemas mucoadesivos para liberação de fármacos.

Corrositex®, BCOP and HET-CAM as alternative methods to animal experimentation / Corrositex®, BCOP e HET-CAM como métodos alternativos à experimentação animal

Tests in animals are used as models in toxicological and investigative studies. However, such tests have been considered inhumane because they can cause pain and suffering to experimental animals, while these methods can often be subjective. Protests calling for animal protection have questioned the effectiveness of in vivo tests and suggest the introduction of alternative, in vitro methods. International organizations, such as the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), the National Institute of Health (NIH), the Organization for Economic Co-operation and Development (OECD), that regulate and develop new alternative animal models, have indicated the running of preliminary assays and execution of sequential tests, which consider physical-chemical properties and data of in vitro assays, before performing in vivo studies. Towards this background, the objective of the present article was to select promising alternative methods such as Corrositex®, BCOP and HET-CAM, intended to refine or replace the use of animals and reduce their suffering.

Testes em animais são utilizados como modelos em estudos toxicológicos e de pesquisa. Entretanto, tais testes têm sido considerados desumanos, porque causam dor e sofrimento aos animais experimentais, porquanto estes métodos podem, freqüentemente, ser subjetivos. Protestos clamando pela proteção animal têm questionado a eficácia dos testes in vivo e sugerem a introdução de métodos alternativos in vitro. Organizações internacionais, tais como Comitê de Coordenação Interagências de Métodos de Validação Alternativos (ICCVAM), Instituto Nacional de Saúde (NIH), Organização para Cooperação Econômica e Desenvolvimento (OECD), que regulam e desenvolvem novos métodos alternativos aos modelos animais, indicaram a realização de ensaios preliminares e a execução de testes seqüenciais, que consideram as propriedades físico-químicas e os dados dos ensaios in vitro, antes de efetuarem estudos in vivo. Nessa direção, o objetivo do presente artigo foi selecionar métodos alternativos promissores, tais como Corrositex®, BCOP e HET-CAM, com o intuito de aperfeiçoar ou substituir o uso de animais e reduzir seus sofrimento.