Preparation and characterization of poly(lactic-co-glycolic acid) microspheres loaded with a labile antiparkinson prodrug
Identifieur interne : 000F36 ( PascalFrancis/Curation ); précédent : 000F35; suivant : 000F37Preparation and characterization of poly(lactic-co-glycolic acid) microspheres loaded with a labile antiparkinson prodrug
Auteurs : E. D'Aurizio [Italie] ; C. F. Van Nostrum [Pays-Bas] ; M. J. Van Steenbergen [Pays-Bas] ; P. Sozio [Italie] ; F. Siepmann [France] ; J. Siepmann [France] ; W. E. Hennink [Pays-Bas] ; A. Di Stefano [Italie]Source :
- International journal of pharmaceutics [ 0378-5173 ] ; 2011.
Descripteurs français
- Pascal (Inist)
- Préparation, Caractérisation, Copolymère, Lactique acide copolymère, Glycolique acide copolymère, Microsphère, Antiparkinsonien, Promédicament, Maladie de Parkinson, Lévodopa, Acide 1,2-dithiolane-3-valérique, Hydrolyse, Cinétique, Lactique acide polymère, Glycolique acide polymère, Libération, Technologie pharmaceutique, Lactone copolymère, Lactone polymère, Polymère aliphatique.
English descriptors
- KwdEn :
- Aliphatic polymer, Antiparkinson agent, Characterization, Copolymer, Glycolic acid copolymer, Glycolic acid polymer, Hydrolysis, Kinetics, Lactic acid copolymer, Lactic acid polymer, Lactone copolymer, Lactone polymer, Levodopa, Microsphere, Parkinson disease, Pharmaceutical technology, Preparation, Prodrug, Release, Thioctic acid.
Abstract
L-Dopa-α-lipoic acid (LD-LA) is a new multifunctional prodrug for the treatment of Parkinson's disease. In human plasma, LD-LA catechol esters and amide bonds are chemically and enzymatically cleaved, respectively, resulting in a half-life time of about fifty minutes. In the present work, the unstable LD-LA was entrapped into biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres designed as depot systems to protect this prodrug against degradation and to obtain a sustained release of the intact compound. The microspheres were prepared by an oil-in-water emulsion/solvent evaporation technique and the effect of formulation and processing parameters (polymer concentration in the organic solvent, volumes ratio of the phases, rate of the organic solvent evaporation) on microspheres characteristics (size, loading, morphology, release) was investigated. Also emphasis was given on the stability of the drug before and after release as well as on the underlying mass transport mechanisms controlling LD-LA release. Interestingly, when encapsulated in appropriate conditions into PLGA microspheres, the labile prodrug was stabilized and released via Fickian diffusion up to more than one week.
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<front><div type="abstract" xml:lang="en">L-Dopa-α-lipoic acid (LD-LA) is a new multifunctional prodrug for the treatment of Parkinson's disease. In human plasma, LD-LA catechol esters and amide bonds are chemically and enzymatically cleaved, respectively, resulting in a half-life time of about fifty minutes. In the present work, the unstable LD-LA was entrapped into biodegradable poly(lactic-co-glycolic acid) (PLGA) microspheres designed as depot systems to protect this prodrug against degradation and to obtain a sustained release of the intact compound. The microspheres were prepared by an oil-in-water emulsion/solvent evaporation technique and the effect of formulation and processing parameters (polymer concentration in the organic solvent, volumes ratio of the phases, rate of the organic solvent evaporation) on microspheres characteristics (size, loading, morphology, release) was investigated. Also emphasis was given on the stability of the drug before and after release as well as on the underlying mass transport mechanisms controlling LD-LA release. Interestingly, when encapsulated in appropriate conditions into PLGA microspheres, the labile prodrug was stabilized and released via Fickian diffusion up to more than one week.</div>
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<s5>08</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Maladie de Parkinson</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Parkinson disease</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Parkinson enfermedad</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Lévodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Levodopa</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>10</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Acide 1,2-dithiolane-3-valérique</s0>
<s2>NK</s2>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Thioctic acid</s0>
<s2>NK</s2>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Tióctico ácido</s0>
<s2>NK</s2>
<s5>11</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Hydrolyse</s0>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Hydrolysis</s0>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>Hidrólisis</s0>
<s5>12</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Cinétique</s0>
<s5>13</s5>
</fC03>
<fC03 i1="13" i2="X" l="ENG"><s0>Kinetics</s0>
<s5>13</s5>
</fC03>
<fC03 i1="13" i2="X" l="SPA"><s0>Cinética</s0>
<s5>13</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE"><s0>Lactique acide polymère</s0>
<s2>NK</s2>
<s5>14</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG"><s0>Lactic acid polymer</s0>
<s2>NK</s2>
<s5>14</s5>
</fC03>
<fC03 i1="14" i2="X" l="SPA"><s0>Láctico ácido polímero</s0>
<s2>NK</s2>
<s5>14</s5>
</fC03>
<fC03 i1="15" i2="X" l="FRE"><s0>Glycolique acide polymère</s0>
<s2>NK</s2>
<s5>15</s5>
</fC03>
<fC03 i1="15" i2="X" l="ENG"><s0>Glycolic acid polymer</s0>
<s2>NK</s2>
<s5>15</s5>
</fC03>
<fC03 i1="15" i2="X" l="SPA"><s0>Glicólico ácido polímero</s0>
<s2>NK</s2>
<s5>15</s5>
</fC03>
<fC03 i1="16" i2="X" l="FRE"><s0>Libération</s0>
<s5>16</s5>
</fC03>
<fC03 i1="16" i2="X" l="ENG"><s0>Release</s0>
<s5>16</s5>
</fC03>
<fC03 i1="16" i2="X" l="SPA"><s0>Liberación</s0>
<s5>16</s5>
</fC03>
<fC03 i1="17" i2="X" l="FRE"><s0>Technologie pharmaceutique</s0>
<s5>23</s5>
</fC03>
<fC03 i1="17" i2="X" l="ENG"><s0>Pharmaceutical technology</s0>
<s5>23</s5>
</fC03>
<fC03 i1="17" i2="X" l="SPA"><s0>Tecnología farmacéutica</s0>
<s5>23</s5>
</fC03>
<fC03 i1="18" i2="X" l="FRE"><s0>Lactone copolymère</s0>
<s2>NK</s2>
<s5>24</s5>
</fC03>
<fC03 i1="18" i2="X" l="ENG"><s0>Lactone copolymer</s0>
<s2>NK</s2>
<s5>24</s5>
</fC03>
<fC03 i1="18" i2="X" l="SPA"><s0>Lactona copolímero</s0>
<s2>NK</s2>
<s5>24</s5>
</fC03>
<fC03 i1="19" i2="X" l="FRE"><s0>Lactone polymère</s0>
<s2>NK</s2>
<s5>25</s5>
</fC03>
<fC03 i1="19" i2="X" l="ENG"><s0>Lactone polymer</s0>
<s2>NK</s2>
<s5>25</s5>
</fC03>
<fC03 i1="19" i2="X" l="SPA"><s0>Lactona polímero</s0>
<s2>NK</s2>
<s5>25</s5>
</fC03>
<fC03 i1="20" i2="X" l="FRE"><s0>Polymère aliphatique</s0>
<s5>26</s5>
</fC03>
<fC03 i1="20" i2="X" l="ENG"><s0>Aliphatic polymer</s0>
<s5>26</s5>
</fC03>
<fC03 i1="20" i2="X" l="SPA"><s0>Polímero alifático</s0>
<s5>26</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Microparticule</s0>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Microparticle</s0>
<s5>37</s5>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Micropartícula</s0>
<s5>37</s5>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Pathologie de l'encéphale</s0>
<s5>38</s5>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Cerebral disorder</s0>
<s5>38</s5>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Encéfalo patología</s0>
<s5>38</s5>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Syndrome extrapyramidal</s0>
<s5>39</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Extrapyramidal syndrome</s0>
<s5>39</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Extrapiramidal síndrome</s0>
<s5>39</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>Maladie dégénérative</s0>
<s5>40</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>Degenerative disease</s0>
<s5>40</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>Enfermedad degenerativa</s0>
<s5>40</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Pathologie du système nerveux central</s0>
<s5>41</s5>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Central nervous system disease</s0>
<s5>41</s5>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Sistema nervosio central patología</s0>
<s5>41</s5>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Pathologie du système nerveux</s0>
<s5>42</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Nervous system diseases</s0>
<s5>42</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Sistema nervioso patología</s0>
<s5>42</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Agoniste</s0>
<s5>43</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Agonist</s0>
<s5>43</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Agonista</s0>
<s5>43</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Récepteur dopaminergique D2</s0>
<s5>44</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>D2 Dopamine receptor</s0>
<s5>44</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Receptor dopaminérgico D2</s0>
<s5>44</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Antioxydant</s0>
<s5>45</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Antioxidant</s0>
<s5>45</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Antioxidante</s0>
<s5>45</s5>
</fC07>
<fN21><s1>157</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>
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