Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach.
10.1016/j.apsb.2018.03.008
- Author:
Elisabetta PANCANI
1
;
Mario MENENDEZ-MIRANDA
1
;
Alexandra PASTOR
1
;
François BRISSET
2
;
Marie-Françoise BERNET-CAMARD
3
;
Didier DESMAËLE
4
;
Ruxandra GREF
1
Author Information
1. Institut de Sciences Moléculaires d'Orsay (ISMO), Univ. of Paris-Sud, Université Paris-Saclay, Orsay 91405, France.
2. Institut de Chimie Moléculaire et des Matériaux d'Orsay (ICMMO), Univ. of Paris-Sud, Université Paris-Saclay, Orsay 91405, France.
3. EA4043 "Unité Bactéries Pathogènes et Santé" (UBaPS), Univ. of Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, France.
4. Institut Galien, UMR8612 Univ. of Paris-Sud, Université Paris-Saclay, Châtenay-Malabry 92290, France.
- Publication Type:Journal Article
- Keywords:
Antibiotic;
Crystalline drug;
Drug-initiated polymerization;
Nanoparticle;
Nanoprecipitation;
Pipemidic acid
- From:
Acta Pharmaceutica Sinica B
2018;8(3):420-431
- CountryChina
- Language:English
-
Abstract:
Nowadays, biodegradable polymers such as poly(lactic acid) (PLA), poly(D,L-lactic--glycolic acid) (PLGA) and poly(-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% (/). 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.
