Potential Nanospray Inhalation of Remdesivir and Hydroxychloroquine using Poly (lactic-co-glycolic) Acid as Fast Delivery for Covid-19 Treatment.

Abstract

Introduction: The oral medication of remdesivir and hydroxychloroquine face several limitations in covid-19 therapy. Despite having the first-pass metabolism, it also has a limitation in the patient who has hospitalised with a severe covid-19 infection. It is especially for a drug that is targeting the angiotensin-converting enzyme II (ACE2) receptor where the receptors are found abundantly in the lung, kidney, heart, and gastrointestinal tract. Therefore, an alternative delivery such as nanospray inhalation would provide a great benefit to those patients. Methods: Scientific sources from Scopus, PubMed, Google Scholar, EBSCO, ScienceDirect, and Elsevier were accessed for publication of this review article regarding the nanospray inhalation for Covid-19. Results: Since the main organ infected by SARS-CoV-2 is the esophagus and lung, inhalation may be the best route to deliver the drug to the site of action. It is proposed that poly (lactic-co-glycolic) acid to be used in the formulation. Conclusion: Poly (lactic-co-glycolic) acid (PLGA) is considered a suitable polymer since it is biocompatible and noncytotoxic, it is the most widely applied in drug delivery either as carrier or excipient for the optimal formulation and distribution of the drugs. Dry powder inhalation of remdesivir and hydroxychloroquine may be an alternative way to deliver the drug against Covid-19.

Remdesivir-loaded bis-MPA hyperbranched dendritic nanocarriers for pulmonary delivery

“…Based on the release measurements in PBS pH 7.4 after 48 h, the dissolved remdesivir was calculated to be 0.24 mg mL −1 , while the resulting concentration of the dissolved bis-MPA nanocarriers in the PBS solution was 1.43 mg mL −1 . The obtained results indicate the enhanced aqueous solubility of remdesivir, induced by its formulation with the bis-MPA (G4-PEG6k-OH) dendritic scaffold, and favorably compare to other literature reported results on remdesivir nanocarriers [ 17 , 18 ] and formulations with Tween-80, PEG-400, or sulfobutylether-beta-cyclodextrin (SBECD) [ 48 ]. The release data of remdesivir from the RHDSs were fitted to several kinetic equations (zero order, first order, Higuchi, Korsmeyer-Peppas, Hixson-Crowell).…”

“…The size range of the generated nano-formulations is considered suitable for efficient cell uptake and low immunogenic response [ 41 ]. Most importantly, it is ideal for respiratory tract direct applications, as inhalation of powder particles with diameters below 5 μm can lead to the efficient delivery into the lower part of the respiratory tract [ 17 ].…”

“…Within this framework, in continuation of our investigations in nano-formulations for effective and safe delivery of hydrophobic cargo [ 21 , 22 ], and aspiring to contribute to the above reported efforts [ [16] , [17] , [18] ] for an inhaled formulation of remdesivir, we present herein the employment of the dendritic-linear-dendritic (DLD) bis-MPA hyperbranched dendritic scaffold (HDS, and specifically, the bis-MPA PEG6k-OH, pseudo generation 4, Fig. S2 , Supplementary Materials) in the synthesis of remdesivir-loaded nano-formulations.…”

“…In recent publications, anti-inflammatorry dexamethazone - the first drug to show life-saving efficacy in patients infected with SARS-CoV-2 - is investigated as a liposomal formulation targeting pulmonary macrophages or other immune cells for more effective anti-oedema and anti-fibrotic effect [ 16 ]. Furthermore, nanospray inhalation of remdesivir and hydroxychloroquinone using poly(lactic-co-glycolic) acid nanocarriers [ 17 ], as well as aerosolized remdesivir nanoliposomal carriers [ 18 ], are proposed as effective alternatives for COVID-19 treatment. As the SARS-CoV-2 infects primarily through the respiratory tract (upper airways and lungs) and mainly affects the lungs, the use of inhaled delivery becomes increasingly important for the non-invasive, quick and direct administration of therapeutics [ 19 ].…”