Quantification of drug loading in polymeric nanoparticles using AFM-IR technique: a novel method to map and evaluate drug distribution in drug nanocarriers

Ural, Merve Seray; Dartois, E.; Mathurin, Jérémie; Desmaële, Didier; Collery, Philippe; Dazzi, Alexandre; Deniset‐Besseau, Ariane; Gref, Ruxandra

doi:10.1039/d2an01079h

Cited by 4 publications

(1 citation statement)

References 33 publications

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“…TEM and SEM techniques are useful, yet the shrinking and melting of these polymeric systems are frequently observed under electron beam incidence [18] as well as artifacts related to staining and coating [48]. The AFM technique in tapping mode has been employed recently to obtain information regarding the morphology [48,49], particle dispersion, stiffness, deformation [45,46], encapsulation [50], tip interaction with the surface [51], and surface porosity of nanospheres [52] and nanocapsules [18,45,46]. For these types of polymer nanocapsules, AFM provides much more additional physical information than electron microscopy.…”

Section: Discussionmentioning

confidence: 99%

Polyester Nanocapsules for Intravenous Delivery of Artemether: Formulation Development, Antimalarial Efficacy, and Cardioprotective Effects In Vivo

et al. 2022

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Artemether (ATM) is an effective antimalarial drug that also has a short half-life in the blood. Furthermore, ATM is also cardiotoxic and is associated with pro-arrhythmogenic risks. We aimed to develop a delivery system enabling the prolonged release of ATM into the blood coupled with reduced cardiotoxicity. To achieve this, we prepared polymeric nanocapsules (NCs) from different biodegradable polyesters, namely poly(D,L-lactide) (PLA), poly-ε-caprolactone (PCL), and surface-modified NCs, using a monomethoxi-polyethylene glycol-block-poly(D,L-lactide) (PEG5kDa-PLA45kDa) polymer. Using this approach, we were able to encapsulate high yields of ATM (>85%, 0–4 mg/mL) within the oily core of the NCs. The PCL-NCs exhibited the highest percentage of ATM loading as well as a slow release rate. Atomic force microscopy showed nanometric and spherical particles with a narrow size dispersion. We used the PCL NCs loaded with ATM for biological evaluation following IV administration. As with free-ATM, the ATM-PCL-NCs formulation exhibited potent antimalarial efficacy using either the “Four-day test” protocol (ATM total at the end of the 4 daily doses: 40 and 80 mg/kg) in Swiss mice infected with P. berghei or a single low dose (20 mg/kg) of ATM in mice with higher parasitemia (15%). In healthy rats, IV administration of single doses of free-ATM (40 or 80 mg/kg) prolonged cardiac QT and QTc intervals and induced both bradycardia and hypotension. Repeated IV administration of free-ATM (four IV doses at 20 mg/kg every 12 h for 48 h) also prolonged the QT and QTc intervals but, paradoxically, induced tachycardia and hypertension. Remarkably, the incorporation of ATM in ATM-PCL-NCs reduced all adverse effects. In conclusion, the encapsulation of ATM in biodegradable polyester NCs reduces its cardiovascular toxicity without affecting its antimalarial efficacy.

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