Assessment of Awareness and Adoption of Fish Farming Technologies in Obio-Akpor Local Government Area of Rivers State, Nigeria

Abstract

Introduction: Inhaled treprostinil (Tyvaso) for pulmonary arterial hypertension (PAH) is dosed 4 times daily. In an effort to reduce dosing frequency, the effects of inhaled treprostinil ester prodrugs (TPD) formulated in lipid nanoparticles (LNP) were studied in a rat model of acute hypoxia-induced hypertension. Methods: TPDs were synthetized by addition of alkyl chains to the carboxyl group, and their conversion to TRE was assessed in vitro in aqueous media and in homogenized lung tissue. For in vivo studies, anesthetized-ventilated rats were monitored for pulmonary arterial pressure (PAP), systemic blood pressure (BP) and heart rate (HR) under hypoxic conditions (FIO2[~]0.10, SaO2[~]50 %) before and after nebulization of the drugs. Drug concentration in blood samples and lungs excised at the end of the study were measured using LC/MS/MS analysis. Results: TPDs improved retention of TRE in LNP. The conversion of TPD to active TRE was slow and chain-length dependent. In rats, nebulized TPD (15 nmole/kg), unlike TRE, had significant reductions in PAP that persisted well beyond 2h. The long-chain TPD formulations (alkyl chains of lengths C12, C14, and C16) exhibited greater bioactivity at relatively low levels of TRE in the blood and high concentrations of TPDs in the lungs. Conclusions: In a rat model of acute hypoxia-induced hypertension, inhaled LNP formulations of treprostinil prodrug demonstrate an extended duration of activity compared to the free form of TRE. The longer chain prodrugs of treprostinil (C12, C14, and C16) exhibit the greater duration in activity and are the focus of additional investigations to assess longer term PK.