Recebido em 28/10/02; aceito em 27/2/03 PHYSICOCHEMICAL CHARACTERIZATION AND STABILITY OF THE POLYMERIC NANOPARTICLE SYSTEMS FOR DRUG ADMINISTRATION. Polymeric nanoparticle systems such as nanocapsules and nanospheres present potential applications for the administration of therapeutic molecules. The physico-chemical characteristics of nanoparticle suspensions are important pre-requisites of the success of any dosage form development. The purpose of this review is to present the state of the art regarding the physico-chemical characterization of these drug carriers, in terms of the particle size distribution, the morphology, the polymer molecular weight, the surface charge, the drug content and the in vitro drug release profiles. Part of the review is devoted to the description of the techniques to improve the stability of colloidal systems.Keywords: nanoparticles; polymers; characterization. INTRODUÇÃOO controle da liberação de fármacos em sítios de ação específi-cos, através da utilização de vetores, capazes de permitir a otimização da velocidade de cedência e do regime de dosagem das substâncias, tem sido uma área de intensa pesquisa nos últimos dez anos. Dentre os vetores, incluem-se as micropartículas e os sistemas coloidais (lipossomas e nanopartículas). As nanopartículas, constituídas por polímeros biodegradáveis, têm atraído maior atenção dos pesquisadores em relação aos lipossomas, devido às suas potencialidades terapêuticas, à maior estabilidade nos fluídos biológicos e durante o armazenamento 1-3 . As nanopartículas poliméricas são sistemas carreadores de fármacos que apresentam diâmetro inferior a 1 µm. O termo nanopartícula inclui as nanocápsulas e as nanoesferas, as quais diferem entre si segundo a composição e organização estrutural (Figura 1). As nanocápsulas são constituídas por um invólucro polimérico disposto ao redor de um núcleo oleoso, podendo o fármaco estar dissolvido neste núcleo e/ou adsorvido à parede polimérica. Por outro lado, as nanoesferas, que não apresentam óleo em sua composição, são formadas por uma matriz polimérica, onde o fármaco pode ficar retido ou adsorvido 2,4,5 . Estes sistemas têm sido desenvolvidos visando inúmeras aplicações terapêuticas, sendo planejados, principalmente, para administração parenteral, oral ou oftálmica. Uma das áreas mais promissoras na utilização das nanopartículas é a vetorização de fármacos anticancerígenos 2,6-8 e de antibióticos 2,9,10 , principalmente através de administração parenteral, almejando uma distribuição mais seletiva dos mesmos e, assim, um aumento do índice terapêutico. Com relação à administração oral de nanopartículas, as pesquisas têm sido direcionadas especialmente à: a) diminuição dos efeitos colaterais de certos fármacos, destacando-se os antiinflamatórios não-esteróides (diclofenaco 11,12 , indometacina 13-15 ), os quais causam freqüentemente irritação à mucosa gastrintestinal e b) proteção de fármacos degradáveis no trato gastrintestinal, como peptídeos 16,17 , proteínas 8,18 e/ou hormônios 19 , aumentando a biodisponi...

This review presents an overview about pharmaceutical and cosmetic topical products containing polymeric nanoparticles (nanospheres and nanocapsules), reporting the main preparation and characterization methods and the studies of penetration and transport of substances through the skin. The penetration and transport extent of those systems through the skin depends on the ingredients chemical composition, on the encapsulation mechanism infl uencing the drug release, on the size of nanoparticles and on the viscosity of the formulations. The polymeric nanoparticles are able to modify the activity of drugs, delay and control the drug release, and increase the drug adhesivity or its time of permanence in the skin. Briefl y, the nanoparticles can be useful as reservoirs of lipophilic drugs to deliver them in the stratum corneum becoming an important strategy to control their permeation into the skin.

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Based on the structure of polymeric nanocapsules containing a lipid-dispersed core composed of caprylic/capric trygliceride (CCT) and sorbitan monostearate (SM), we hypothesized that varying the core component concentrations the drug release kinetic could be modulated. Our objective was also to determine the parameters which were responsible for controlling the drug release kinetics. The nanocapsules were prepared by interfacial deposition of poly(epsilon-caprolactone). Interfacial hydrolysis of indomethacin ester (IndOEt) was used to simulate a sink condition of release. Mathematical modeling showed that the IndOEt half-lives increased (198 to 378 and 263 to 508 min) with the increase in the core lipid concentrations, and that the release mechanism was the anomalous transport. By increasing the SM concentration, the diameters were constant (around 250 nm) and the surface areas increased (from 1 06 × 10 4 to 1 51 × 10 4 cm 2 · ml −1 ), while by increasing the CCT concentration, the diameters increased (215 to 391 nm) and the surface areas reduced (1 46 × 10 4 to 1 06 × 10 4 cm 2 · ml −1 ). The presence of SM increased the viscosity of CCT and the IndOEt apparent permeability decreased from 4 26 × 10 −7 to 2 54 × 10 −7 cm · s −1 , while for CCT series, the apparent permeability was constant around 3 0 × 10 −7 cm · s −1 . A mathematical correlation was established and the IndOEt apparent permeability can be estimated by the SM concentration. In conclusion, varying the CCT and SM concentrations the IndOEt release was controlled by the nanocapsule surface area and by the viscosity of the core, respectively.

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