Context: Lipid-polymer hybrid nanoparticles (LPNPs) are polymeric nanoparticles enveloped by lipid layers, which have emerged as a potent therapeutic nanocarrier alternative to liposomes and polymeric nanoparticles. Objective: The aim of this work was to develop, characterize and evaluate LPNPs to deliver a model protein, lysozyme. Materials and methods: Lysozyme-loaded LPNPs were prepared by using the modified w/o/w double-emulsion-solvent-evaporation method. Poly-ɛ-caprolactone (PCL) was used as polymeric core material and tripalmitin:lechitin mixture was used to form a lipid shell around the LPNPs. LPNPs were evaluated for particle size distribution, zeta potential, morphology, encapsulation efficiency, in vitro drug release, stability and cytotoxicity. Results: The DLS measurement results showed that the particle size of LPNPs ranged from 58.04 ± 1.95 nm to 2009.00 ± 0.52 nm. The AFM and TEM images of LPNPs demonstrate that LPNPs are spherical in shape. The protein-loading capacity of LPNPs ranged from 5.81% to 60.32%, depending on the formulation parameters. LPNPs displayed a biphasic drug release pattern with a burst release within 1 h, followed by sustained release afterward. Colloidal stability results of LPNPs in different media showed that particle size and zeta potential values of particles did not change significantly in all media except of FBS 100% for 120 h. Finally, the results of a cellular uptake study showed that LPNPs were significantly taken up by 83.3% in L929 cells. Conclusion: We concluded that the LPNPs prepared with PCL as polymeric core material and tripalmitin:lechitin mixture as lipid shell should be a promising choice for protein delivery.

Combination therapy using anticancer drugs and nucleic acid is a more promising strategy to overcome multidrug resistance in cancer and to enhance apoptosis. In this study, lipid-polymer hybrid nanoparticles (LPNs), which contain both pemetrexed and miR-21 antisense oligonucleotide (anti-miR-21), have been developed for treatment of glioblastoma, the most aggressive type of brain tumor. Prepared LPNs have been well characterized by particle size distribution and zeta potential measurements, determination of encapsulation efficiency, and in vitro release experiments. Morphology of LPNs was determined by transmission electron microscopy. LPNs had a hydrodynamic size below 100 nm and exhibited sustained release of pemetrexed up to 10 h. Encapsulation of pemetrexed in LPNs increased cellular uptake from 6% to 78%. Results of confocal microscopy analysis have shown that co-delivery of anti-miR-21 significantly improved accumulation of LPNs in the nucleus of U87MG cells. Nevertheless, more effective cytotoxicity results could not be obtained due to low concentration of anti-miR-21, loaded in LPNs. We expect that the effective drug delivery systems can be obtained with higher concentration of anti-miR-21 for the treatment of glioblastoma.

In this study, ciprofloxacin hydrochloride (CIP)-loaded poly-ε-caprolactone (PCL) nanoparticles were prepared for pulmonary administration. CIP-loaded PCL nanoparticles were prepared using solid-in-oil-in-water (s/o/w) emulsion solvent evaporation method, and the effects of various formulation parameters on the physicochemical properties of the nanoparticles were investigated. PCL nanoparticles showed spherical shapes with particle sizes around 143–489 nm. Encapsulation efficiency was found to be very low because of water-solubility properties of CIP. However, the surface modification of nanoparticles with chitosan caused an increase in the encapsulation efficiency of nanoparticles. At drug release study, CIP-loaded PCL nanoparticles showed initial burst effect for 4 h and then continuously released for 72 h. Nanocomposite microparticles containing CIP-loaded PCL nanoparticles were prepared freeze-drying method and mannitol was used as carrier material. Tapped density and MMADt results show that nanocomposite microparticles have suitable aerodynamic properties for pulmonary administration. Antimicrobial efficacy investigations showed that CIP-encapsulated PCL nanoparticles and nanocomposite microparticles inhibited the growth of bacteria. Also, when the antimicrobial activity of the nanoparticles at the beginning and at the sixth month was examined, it was found that the structure of the particulate system was still preserved. These results indicated that nanocomposite microparticles containing CIP-loaded PCL nanoparticles can be used for pulmonary delivery.

In this study, recombinant human interleukin-2 (rhIL-2) containing poly(lactic-co-glycolic acid) (PLGA) microparticles were prepared for pulmonary administration by modified w/o/w double emulsion solvent extraction method and the effects of various formulation parameters on the physicochemical properties of the microparticles were investigated. Microparticles in suitable size for pulmonary administration (4.02 µm) were obtained by increasing dichloromethane volume used in the organic phase. Also, a very high encapsulation efficiency (99.22%) value could be reached in these microparticles. In the sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis, rhIL-2 extracted from microparticles having a similar band with native rhIL-2 showed that the protein was not affected by the encapsulation process. The release curves of microparticles exhibited a biphasic fashion, characterized by a fast release phase at initial 1 day, followed by a slower one on the remaining days. Bioactivity investigations using T cells show that rhIL-2 encapsulated in PLGA microparticles retain their biological activity.

Objective: The aim of this study was the preparation and evaluation of dry powder formulations of recombinant human interleukin-2 (rhIL-2)-loaded microparticles to be administered to the lung by inhalation. Methods: As indicated in our previous study, the microparticles were prepared by modified water-in-oil-in-water (w₁/o/w₃) double emulsion solvent extraction method using poly(lactic-co-glycolic acid) (PLGA) polymers. The dry powder formulations were prepared with blending of microparticles and mannitol as a coarse carrier. The actual aerodynamic characteristics of the microparticles alone and prepared mixtures with mannitol are evaluated by using the eight-stage Andersen cascade impactor. Results: Due to the low tapped density of microparticles (<0.4 g/cm³), the theoretical aerodynamic diameter (MMADt) values were calculated (90% of the capsule content was determined to be released. However, the actual aerodynamic diameter (MMADa) values were seen to be higher than the MMADt values. The blending of the microparticles with mannitol allowed their aerodynamic diameters to decrease and their fine particle fraction values to increase. Conclusion: The obtained results have shown that the mixing of rhIL-2-loaded microparticles with mannitol possess suitable aerodynamic characteristics to be administered to the lungs by inhalation.