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: 3.65). 12/2002; 248(1-2):149-56. DOI: 10.1016/S0378-5173(02)00431-3
Source: PubMed


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.

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    • "These studies and others have highlighted the biocompatibility of such biodegradable polymers as poly(methylidene malonate) (Tamargo et al., 2002) and poly(␧-caprolactone) (Li et al., 2007). Among biodegradable polymers, poly(lactic-co-glycolic acid) (PLGA) has been widely studied (Dorta et al., 2002; Loo et al., 2004) and has been used to form solid scaffolds (Kim et al., 2010; Yoon et al., 2003), injectable implants (Choi et al., 2005; Wang et al., 2010) and encapsulated nanoparticles (Gomez-Graete et al., 2007; Liu et al., 2007), or microparticles (Galeska et al., 2005; Hickey et al., 2002; Jaraswekin et al., 2007; Zolnik and Burgess, 2008). The ability of such biodegradable polymers to be loaded with clinically relevant drugs has also been demonstrated (Manome et al., 2006). "
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    ABSTRACT: A novel extrusion printing system was used to create drug delivery structures wherein dexamethasone-21-phosphate disodium salt (Dex21P) was encapsulated within a biodegradable polymer (PLGA) and water soluble poly(vinyl alcohol) (PVA) configurations. The ability to control the drug release profile through the spatial distribution of drug within the printed 3-dimensional structures is demonstrated. The fabricated configurations were characterised by optical microscopy and SEM to evaluate surface morphology. The results clearly demonstrate the successful encapsulation of dexamethasone within a laminated PLGA:PVA structure. The resulting drug release profiles from the structures show a two stage release profile with distinctly different release rates and minimal initial burst release observed. Dexamethasone release was monitored over a 4-month period. This approach clearly demonstrates that the extrusion printing technique provides a facile and versatile approach to fabrication of novel drug delivery platforms.
    International Journal of Pharmaceutics 11/2011; 422(1-2):254-63. DOI:10.1016/j.ijpharm.2011.11.007 · 3.65 Impact Factor
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    • "Two common biodegradable polymers, poly-(∊ caprolactone ) (PCL) and poly(lactide-co-glycolide) (PLGA) would avoid the need for surgical retrieval but required organic solvents for dip coatings and polyesters like PLGA are prone to formation of acidic hydrolysis products. Organic solvents and decreased local pH both represent potential sources of instability for acid sensitive, peptide and protein drugs [38] [40]. Other natural biodegradable polymers like alginate [42] and amylase [15] release drug loads too quickly, becoming highly permeable or disintegrating upon exposure to aqueous body fluids. "
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    ABSTRACT: Due to its unique properties, silk fibroin was studied as a biodegradable polymer vehicle for sustained, local delivery of the anticonvulsant adenosine from encapsulated reservoirs. Silk is a biologically derived protein polymer that is biocompatible, mechanically strong and degrades to non-toxic products in vivo. To achieve local, sustained, controlled adenosine release from fully degradable implants, solid adenosine powder reservoirs were coated with silk fibroin. Material properties of the silk coating including thickness, crystallinity and morphology were investigated to assess the relationships between silk coating biomaterial features and adenosine release from silk encapsulated reservoirs. Reservoir coating thickness was varied through manipulation of the silk coating solution concentration and number of coatings applied. Release studies were also performed in proteinase type XIV to model the effects of degradation. Increasing the barrier to diffusion, either by increasing coating thickness or crystallinity was found to delay adenosine burst, decrease average daily release rate, and increase duration of release. In the case of encapsulated reservoirs coated with eight layers of 8% (w/v) silk, a linear release profile was observed and adenosine release was sustained for 14days. The ability to achieve nearly constant release for 2weeks for adenosine via control of the silk coating suggests these encapsulated reservoirs represent a novel system for delivering adenosine. We anticipate that this approach could also be extended to other implant needs and small-molecule drugs to treat a range of clinical needs.
    Journal of Controlled Release 02/2010; 144(2):159-67. DOI:10.1016/j.jconrel.2010.01.035 · 7.71 Impact Factor
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    • "After a fast release in the first three weeks, likely due to the high fiber surface area and to the solubilization of the drug adsorbed on the fiber surface, the maintenance of the fibrous structure could contribute to the controlled drug release at a fairly constant rate until the end of the study. Conversely cast films were more subjected to bulk-erosion degradation and their drug release profile corresponded to the typical triphase kinetics of monolithic PLGA systems [85] [86]. After the burst release in the first days, likely associated with the removal of superficial RA and with the exchange between the residual solvent entrapped into the film and the release medium, the second phase corresponds to a steady release rate lasting about 50 days. "
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    ABSTRACT: Poly(lactic-co-glycolic acid) (PLGA) meshes loaded with retinoic acid (RA) were prepared by applying the electrospinning technique. The purpose of the present work was to combine the biological effects of RA and the advantages of electrospun meshes to enhancing the mass transfer features of controlled release systems and cell interaction with polymeric scaffolds. The processing conditions for the fabrication of three-dimensional meshes were optimized by studying their influence on mesh morphology. Tensile testing showed that RA loading influenced the meshes' mechanical properties by increasing their strength and rigidity. Moreover, the drug release and degradation profiles of the electrospun systems were compared to analogous RA-loaded PLGA films prepared by solvent casting. The results of this study highlight that the electrospun meshes preserved their fibrous structure after 4 months under in vitro physiological conditions and showed a sustained controlled release of the loaded agent in comparison to that observed for cast films. The bioactivity of the loaded RA was investigated on murine preosteoblasts cells by evaluating its influence on cell proliferation and morphology.
    Acta biomaterialia 09/2009; 6(4):1258-68. DOI:10.1016/j.actbio.2009.08.015 · 6.03 Impact Factor
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