Article

Potential applications of PLGA film-implants in modulating in vitro drugs release

Dpto. Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 Tenerife, Spain.
International Journal of Pharmaceutics (Impact Factor: 3.79). 12/2002; 248(1-2):149-56. DOI: 10.1016/S0378-5173(02)00431-3
Source: PubMed

ABSTRACT In this work we evaluate poly(lactic/glycolic) acid (PLGA) film-implants as potential biodegradable devices for controlled release of two different drugs: 5-Fluorouridine (5-FUR), a conventional low molecular weight water-soluble compound and SPf66 malaria vaccine, a therapeutic synthetic polypeptide. Three types of devices were prepared by solvent-casting techniques alone or combined with compression method: simple monolithic discs (SMD), multilayer discs with a central monolithic layer (MLDM), and multilayer discs with a central drug-reservoir (MLDR). For the highly water-soluble drug, 5-FUR, in vitro release from SMD showed an initial burst (24% in 2 h) followed by prolonged release over 20 days. In contrast, from a MLDM (two drug-free PLGA discs were added to the SMD) showed an initial lag-time of 12 days followed by a very fast second release phase. Finally, when the load of this system was increased from 3 to 9%, an extended release over 20 days with a low burst effect was obtained. For SPf66, the central reservoir containing the synthetic polypeptide MLDR reduces the possibility of degradation due to peptide contact with polymer solution. When four layers were added, 10 days sustained-release was obtained without any burst effect. With six layers a moderate pulse was obtained, 18-22 days from the beginning of the release. The results show the suitability of the proposed devices to control release and avoid the burst effect with highly water-soluble drugs; as well as modulate in vitro peptide release.

0 Followers
 · 
122 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Poly (lactic-co-glycolic acid) (PLGA) is one of the most effective biodegradable polymeric nanoparticles (NPs). It has been approved by the US FDA to use in drug delivery systems due to controlled and sustained- release properties, low toxicity, and biocompatibility with tissue and cells. In the present review, the structure and properties of PLGA copolymers synthesized by ring-opening polymerization of DL-lactide and glicolide were characterized using 1H nuclear magnetic resonance spectroscopy, gel permeation chromatography, Fourier transform infrared spectroscopy and differential scanning calorimetry. Methods of preparation and characterization, various surface modifications, encapsulation of diverse anticancer drugs, active or passive tumor targeting and different release mechanisms of PLGA nanoparticles are discussed. Increasing experience in the application of PLGA nanoparticles has provided a promising future for use of these nanoparticles in cancer treatment, with high efficacy and few side effects.
    Asian Pacific journal of cancer prevention: APJCP 01/2014; 15(2):517-535. DOI:10.7314/APJCP.2014.15.2.517 · 1.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Introducción La reometría de cizalla oscilatoria permite obtener información muy útil acerca de las propiedades mecánicas de los hidrogeles y conocer las mejores condiciones para su preparación (1) y conservación (2). Recientemente esta técnica ha sido aplicada al análisis de una gran variedad de sólidos de diferente espesor, desde lentes de contacto hasta comprimidos (3). Sin embargo, no se dispone de información sobre su aplicación en el análisis de las propiedades de dispersiones poliméricas de poliésteres biodegradables como los copolímeros de D,L-lactida-co-glicolida (PLGA) que se han venido utilizando para el control de la cesión de una gran variedad de fármacos (4). La elaboración de implantes laminares biodegradables formados a partir de este tipo de copolímeros mediante el método de evaporación del disolvente, consiste en formar una dispersión polimérica en la que se ha de distribuir uniformemente el principio activo a incluir en el implante. Ésta distribución y su posterior liberación desde el implante ya formado, dependerá de las propiedades reológicas de la dispersión polimérica. El objeto de este trabajo consistió en el estudio de las propiedades mecánicas de dispersiones de PLGA, su comparación con dispersiones de copolímeros de diferente naturaleza como el PLA-PEG, para relacionarlas en posteriores trabajos con el comportamiento de los implantes laminares elaborados, la distribución del principio activo en los mismos y su liberación. Materiales y Métodos Los polímeros empleados en este trabajo fueron sintetizados en nuestro laboratorio mediante polimerización por apertura del anillo. Los métodos de síntesis para la obtención del PLGA y del PLA-PEG, fueron los desarrollados por Gilding y Reed (5) y Gref y col. (6) respectivamente. El peso molecular de los polímeros sintetizados se determinó mediante cromatografía de perrmeación en gel (GPC), previa calibración con patrones de poliestireno (2.800-355.000 Da), empleando tetrahidrofurano (THF) como fase móvil a una velocidad de flujo de 0.9 mL/min. La composición de los polímeros se caracterizó mediante resonancia magnética nuclear del protón (RMN-1 H), empleando un espectrómetro Bruker AMX-400 y usando cloroformo deuterado como disolvente. Las proporciones relativas de los enlaces láctico-glicólico (LA-GA) y glicólico-glicólico (GA-GA) se determinaron mediante RMN del carbono (RMN-13 C) a 100.61 MHz y empleando como disolvente dimetilsulfóxido deuterado. En la tabla 1 se recogen las características más importantes de los polímeros sintetizados. Tabla 1. Características de los polímeros.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The purpose of this study was to understand the impact of the poly (lactic-co-glycolic acid) (PLGA) molecular behavior in the feed solution on the drug release kinetics of PLGA microparticles prepared via spray drying. The PLGA molecular behavior in the feed solutions were characterized by using tube viscometry, which provides information about the polymer coil radius (R-coil), the Martin constant (K-m), and the overlap concentration (c*). The particle size and the drug surface enrichment were investigated by using scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), respectively. The drug release profiles were characterized by using the USP paddle method and analyzed by using the Crank's diffusion model to calculate the kinetic parameters. Multivariate data analysis using principal component analysis (PCA) was employed to display the relationship between the PLGA molecular behavior, particle properties and the drug release kinetics from the spray dried PLGA microparticles. Rheological studies suggested that an increased molar ratio of a poor solvent (methanol) in the solvent system resulted in a decreased R-coil, the increase in K-m and c*. The higher effective diffusion coefficient of drug calculated by using the Crank's diffusion model was observed in the polymer matrix prepared at an acetone-to-methanol molar ratio of 69:31. The PCA models indicated that the drug surface enrichment and the K-m were directly proportional to the drug burst release, while the entanglement index was inversely correlated. Further, the particle size had a less significant impact on the drug burst release. This study implies that the polymer molecular behavior would influence the microscopic connectivity and diffusivity of polymer matrix, which eventually affects the drug release kinetics.
    Polymer 10/2013; 54(21-21):5920-5927. DOI:10.1016/j.polymer.2013.08.044 · 3.77 Impact Factor