Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach
Nowadays, biodegradable polymers such as poly(lactic acid) (PLA), poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) remain the most common biomaterials to produce drug-loaded nanoparticles (NPs). Pipemidic acid (PIP) is a poorly soluble antibiotic with a strong tendency to crys...
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| Format: | Article |
| Language: | English |
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Elsevier
2018-05-01
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| Series: | Acta Pharmaceutica Sinica B |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211383517304847 |
| _version_ | 1828889503874416640 |
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| author | Elisabetta Pancani Mario Menendez-Miranda Alexandra Pastor François Brisset Marie-Françoise Bernet-Camard Didier Desmaële Ruxandra Gref |
| author_facet | Elisabetta Pancani Mario Menendez-Miranda Alexandra Pastor François Brisset Marie-Françoise Bernet-Camard Didier Desmaële Ruxandra Gref |
| author_sort | Elisabetta Pancani |
| collection | DOAJ |
| description | Nowadays, biodegradable polymers such as poly(lactic acid) (PLA), poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) remain the most common biomaterials to produce drug-loaded nanoparticles (NPs). Pipemidic acid (PIP) is a poorly soluble antibiotic with a strong tendency to crystallize. PIP incorporation in PLA/PLGA NPs was challenging because of PIP crystals formation and burst release. As PIP had a poor affinity for the NPs, an alternative approach to encapsulation was used, consisting in coupling PIP to PCL. Thus, a PCL–PIP conjugate was successfully synthesized by an original drug-initiated polymerization in a single step without the need of catalyst. PCL–PIP was characterized by NMR, IR, SEC and mass spectrometry. PCL–PIP was used to prepare self-assembled NPs with PIP contents as high as 27% (w/w). The NPs were characterized by microscopy, DLS, NTA and TRPS. This study paves the way towards the production of NPs with high antibiotic payloads by drug-initiated polymerization. Further studies will deal with the synthesis of novel polymer–PIP conjugates with ester bonds between the drug and PCL. PIP can be considered as a model drug and the strategy developed here could be extended to other challenging antibiotics or anticancer drugs and employed to efficiently incorporate them in NPs. KEY WORDS: Pipemidic acid, Nanoparticle, Antibiotic, Nanoprecipitation, Crystalline drug, Drug-initiated polymerization |
| first_indexed | 2024-12-13T12:42:40Z |
| format | Article |
| id | doaj.art-9f8d2c126a2748f3855976b63910d563 |
| institution | Directory Open Access Journal |
| issn | 2211-3835 |
| language | English |
| last_indexed | 2024-12-13T12:42:40Z |
| publishDate | 2018-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Acta Pharmaceutica Sinica B |
| spelling | doaj.art-9f8d2c126a2748f3855976b63910d5632022-12-21T23:45:36ZengElsevierActa Pharmaceutica Sinica B2211-38352018-05-0183420431Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approachElisabetta Pancani0Mario Menendez-Miranda1Alexandra Pastor2François Brisset3Marie-Françoise Bernet-Camard4Didier Desmaële5Ruxandra Gref6Institut de Sciences Moléculaires d’Orsay (ISMO), Univ. of Paris-Sud, Université Paris-Saclay, Orsay 91405, FranceInstitut de Sciences Moléculaires d’Orsay (ISMO), Univ. of Paris-Sud, Université Paris-Saclay, Orsay 91405, FranceInstitut de Sciences Moléculaires d’Orsay (ISMO), Univ. of Paris-Sud, Université Paris-Saclay, Orsay 91405, France; Institut Galien, UMR8612 Univ. of Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, FranceInstitut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Univ. of Paris-Sud, Université Paris-Saclay, Orsay 91405, FranceEA4043 ''Unité Bactéries Pathogènes et Santé'' (UBaPS), Univ. of Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, FranceInstitut Galien, UMR8612 Univ. of Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, FranceInstitut de Sciences Moléculaires d’Orsay (ISMO), Univ. of Paris-Sud, Université Paris-Saclay, Orsay 91405, France; Corresponding author. Tel.: +33 1 69158234.Nowadays, biodegradable polymers such as poly(lactic acid) (PLA), poly(D,L-lactic-co-glycolic acid) (PLGA) and poly(ε-caprolactone) (PCL) remain the most common biomaterials to produce drug-loaded nanoparticles (NPs). Pipemidic acid (PIP) is a poorly soluble antibiotic with a strong tendency to crystallize. PIP incorporation in PLA/PLGA NPs was challenging because of PIP crystals formation and burst release. As PIP had a poor affinity for the NPs, an alternative approach to encapsulation was used, consisting in coupling PIP to PCL. Thus, a PCL–PIP conjugate was successfully synthesized by an original drug-initiated polymerization in a single step without the need of catalyst. PCL–PIP was characterized by NMR, IR, SEC and mass spectrometry. PCL–PIP was used to prepare self-assembled NPs with PIP contents as high as 27% (w/w). The NPs were characterized by microscopy, DLS, NTA and TRPS. This study paves the way towards the production of NPs with high antibiotic payloads by drug-initiated polymerization. Further studies will deal with the synthesis of novel polymer–PIP conjugates with ester bonds between the drug and PCL. PIP can be considered as a model drug and the strategy developed here could be extended to other challenging antibiotics or anticancer drugs and employed to efficiently incorporate them in NPs. KEY WORDS: Pipemidic acid, Nanoparticle, Antibiotic, Nanoprecipitation, Crystalline drug, Drug-initiated polymerizationhttp://www.sciencedirect.com/science/article/pii/S2211383517304847 |
| spellingShingle | Elisabetta Pancani Mario Menendez-Miranda Alexandra Pastor François Brisset Marie-Françoise Bernet-Camard Didier Desmaële Ruxandra Gref Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach Acta Pharmaceutica Sinica B |
| title | Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach |
| title_full | Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach |
| title_fullStr | Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach |
| title_full_unstemmed | Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach |
| title_short | Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach |
| title_sort | nanoparticles with high payloads of pipemidic acid a poorly soluble crystalline drug drug initiated polymerization and self assembly approach |
| url | http://www.sciencedirect.com/science/article/pii/S2211383517304847 |
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