Background: Formulations incorporating nanoparticles (NPs) are widely used to prolong drug release.
In this regard, poly(lactide-co-glicolide) (PLGA) is often used in their preparation due to its high degree of biocompatibility
and biodegradability. In the present study, morphine HCl is incorporated in PLGA-NPs and different
preparation alternatives are evaluated for their effects on the properties, stability and capacity of encapsulation.
Methods: NPs were prepared by a double emulsion solvent diffusion-ammonium loading (DESD-AL) or double
emulsion solvent diffusion-traditional (DESD-T) technique. NP morphology, size, zeta potential and encapsulation
efficiency were investigated. In vitro studies were performed in phosphate buffer pH 7.4 at 37 ºC and deionized
water at 4ºC. Adult male Swiss mice were used to study the pharmacokinetic behavior in vivo.
Results: Our results show that DESD-AL provides a higher level of morphine entrapment and that increasing the
sonication time reduces the size but does not appreciably reduce the entrapment percentage. It was also observed
that NP stability was greater when Pluronic F68 was used rather than PVA, and that in vitro assays provided
better results with low concentrations of both stabilizers. Lyophilized NPs, after rehydration showed properties
that were only slightly different from those of the untreated ones, with no sign of precipitation or aggregation.
Finally, the obtained NPs enhanced morphine bioavailability.
Conclusions: In conclusion, a useful method for encapsulating morphine in order to obtain an extended delivery
period is described and its effects are compared with those of the free drug.