Purpose Letrozole (LTZ), an aromatase inhibitor with poor aqueous solubility, is used as the first line treatment for hormonal sensitive breast cancer in postmenopausal women. The purpose of the current study is to develop hyaluronic acid (HA)/ chitosan (Cs)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of LTZ to improve therapeutic efficacy, control release and minimize side effects of LTZ. Methods PLGA nanoparticles were prepared, and the effect of various parameters on particle size, surface charge, and encapsulation efficiency was extensively studied. The morphology of nanoparticles was visualized using transmission electron microscopy (TEM), and drug-polymer interactions were studied using differential scanning calorimetry (DSC) and Fourier transform-infrared spectroscopy (FT-IR). The in vitro release kinetics and effect of freeze-drying process on the physicochemical characteristics of nanoparticles were also evaluated. Moreover, the in vivo acute toxicities of blank and drug-loaded nanoparticles were assessed. Results PLGA nanoparticles exhibited nanosized (464.3 ± 2.1 nm) spherical particles, negative surface charge (zeta-potential of − 10.5 ± 0.4 mV), and high drug encapsulation efficiency of 63.9 ± 3.7% and sustained drug release pattern over 48 h.The in vivo acute toxicity study revealed that the nanoparticles were well tolerated at a dose of 300 mg/kg. Conclusion HA/Cs-coated PLGA nanoparticles might provide a promising system for LTZ delivery and further investigations could confirm their potential efficacy in breast cancer therapy.

Purpose Letrozole (LTZ), an aromatase inhibitor with poor aqueous solubility, is used as the first line treatment for hormonal sensitive breast cancer in postmenopausal women. The purpose of the current study is to develop hyaluronic acid (HA)/ chitosan (Cs)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of LTZ to improve therapeutic efficacy, control release and minimize side effects of LTZ. Methods PLGA nanoparticles were prepared, and the effect of various parameters on particle size, surface charge, and encapsulation efficiency was extensively studied. The morphology of nanoparticles was visualized using transmission electron microscopy (TEM), and drug-polymer interactions were studied using differential scanning calorimetry (DSC) and Fourier transform-infrared spectroscopy (FT-IR). The in vitro release kinetics and effect of freeze-drying process on the physicochemical characteristics of nanoparticles were also evaluated. Moreover, the in vivo acute toxicities of blank and drug-loaded nanoparticles were assessed. Results PLGA nanoparticles exhibited nanosized (464.3 ± 2.1 nm) spherical particles, negative surface charge (zeta-potential of − 10.5 ± 0.4 mV), and high drug encapsulation efficiency of 63.9 ± 3.7% and sustained drug release pattern over 48 h.The in vivo acute toxicity study revealed that the nanoparticles were well tolerated at a dose of 300 mg/kg. Conclusion HA/Cs-coated PLGA nanoparticles might provide a promising system for LTZ delivery and further investigations could confirm their potential efficacy in breast cancer therapy.

Purpose Letrozole (LTZ), an aromatase inhibitor with poor aqueous solubility, is used as the first line treatment for hormonal sensitive breast cancer in postmenopausal women. The purpose of the current study is to develop hyaluronic acid (HA)/ chitosan (Cs)-coated poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles for the delivery of LTZ to improve therapeutic efficacy, control release and minimize side effects of LTZ. Methods PLGA nanoparticles were prepared, and the effect of various parameters on particle size, surface charge, and encapsulation efficiency was extensively studied. The morphology of nanoparticles was visualized using transmission electron microscopy (TEM), and drug-polymer interactions were studied using differential scanning calorimetry (DSC) and Fourier transform-infrared spectroscopy (FT-IR). The in vitro release kinetics and effect of freeze-drying process on the physicochemical characteristics of nanoparticles were also evaluated. Moreover, the in vivo acute toxicities of blank and drug-loaded nanoparticles were assessed. Results PLGA nanoparticles exhibited nanosized (464.3 ± 2.1 nm) spherical particles, negative surface charge (zeta-potential of − 10.5 ± 0.4 mV), and high drug encapsulation efficiency of 63.9 ± 3.7% and sustained drug release pattern over 48 h.The in vivo acute toxicity study revealed that the nanoparticles were well tolerated at a dose of 300 mg/kg. Conclusion HA/Cs-coated PLGA nanoparticles might provide a promising system for LTZ delivery and further investigations could confirm their potential efficacy in breast cancer therapy.

In this study, PGA-co-PDL nanoparticles (NPs) encapsulating model antigen, bovine serum albumin (BSA), were prepared via double emulsion solvent evaporation. In addition, chitosan hydrochloride (CHL) was incorporated into the external phase of the emulsion solvent method, which resulted in surface adsorption onto the NPs to form hybrid cationic CHL NPs. The BSA encapsulated CHL NPs were encompassed into nanocomposite microcarriers (NCMPs) composed of L-leucine to produce CHL NPs/NCMPs via spray drying. The CHL NPs/NCMPs were investigated for in vitro aerosolization, release study, cell viability and uptake, and stability of protein structure. Hybrid cationic CHL NPs (CHL: 10 mg/mL) of particle size (480.2 ± 32.2 nm), charge (+14.2 ± 0.72 mV), and BSA loading (7.28 ± 1.3 µg/mg) were produced. The adsorption pattern was determined to follow the Freundlich model. Aerosolization of CHL NPs/NCMPs indicated fine particle fraction (FPF: 46.79 ± 11.21%) and mass median aerodynamic diameter (MMAD: 1.49 ± 0.29 µm). The BSA α-helical structure was maintained, after release from the CHL NPs/NCMPs, as indicated by circular dichroism. Furthermore, dendritic cells (DCs) and A549 cells showed good viability (≥70% at 2.5 mg/mL after 4–24 h exposure, respectively). Confocal microscopy and flow cytometry data showed hybrid cationic CHL NPs were successfully taken up by DCs within 1 h of incubation. The upregulation of CD40, CD86, and MHC-II cell surface markers indicated that the DCs were successfully activated by the hybrid cationic CHL NPs. These results suggest that the CHL NPs/NCMPs technology platform could potentially be used for the delivery of proteins to the lungs for immunostimulatory applications such as vaccines.

Chemoenzymatic cascades enable reactions with the high productivity of chemocatalysts and high selectivity of enzymes. Nevertheless, the combination of these different fields of catalysis is prone to mutual deactivation of metal‐ and biocatalysts. In this study, a one‐pot sequential two‐step catalytic cascade reaction was successfully implemented for the synthesis of a methylene‐bridged bis(2‐substituted benzofuran). In the first step, a palladium‐free Sonogashira reaction is used for the synthesis of a benzofuran derivative. In the subsequent step, the formed 2‐substituted benzofuran is hydroxylated by the monooxygenase P450 BM3 variant (A74S‐F87V‐L188Q) and undergoes further elimination reactions. The study proofs that combination of Cu scorpionate catalyzed Sonogashira cross‐coupling and P450 mediated oxidation is possible and results in up to 84 % yield of the final product. The oxidation reaction is boosted by capturing inhibiting reaction components.

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