Pharmaceutical Development of Sodium Hyaluronate Respirable Dry Powders for Targeted Drug Delivery

F. Martinelli, A.G Balducci, A. Kumar, B.Forbes, R.Bettini, F.Buttini

Background: CD44 is the major hyaluronic acid binding receptor involved in pathological conditions, including tumour progression and metastasis formation. It has been reported that CD44 is a protein over-expressed in non-small cell lung tumours.
The aim of this work was to produce sodium hyaluronate (HA) dry powders using a particle engineering approach based on spray drying technique in view of an efficacious platform capable to deliver chemotherapeutics to the lungs.
Methods: Different dry powder formulations were obtained by spray-drying (SD) water/ethanol mixtures containing HA and a selected adjuvant. HA dry powders were characterized in terms of morphology and in vitro respirability. Biocompatibility of excipients and formulations was investigated using A459 cell culture and the MTT test.
Results: Pure HA SD powders showed a poor aerodynamic performance. Three surfactants were included in the formulations (stearylamine, cetostearyl alcohol and stearyl alcohol) at three different proportions (10%, 5% and 1%). Microparticles of HA had a spherical shape with smooth surface; stearylamine led to wrinkled particles whereas cetostearyl and stearyl alcohol kept a roundish shape and some holes were evident onto the surface. Formulations containing 5% of stearylamine showed the best aerodynamic performance (emitted dose of 89% and FPF of 52% of nominal dose).
MTT results ranked the biocompatibility of the excipients: stearylamine < cetostearyl alcohol < stearyl alcohol.
Conclusions: Dry powders suitable for lung delivery were produced by co-spray-drying hyaluronate and surfactants. These might be employed as a platform to directly target tumour cells with antineoplastic drugs.

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