Organic Solution Advanced Spray-Dried Microparticulate/Nanoparticulate Dry Powders of Lactomorphin for Respiratory Delivery: Physicochemical Characterization, In Vitro Aerosol Dispersion, and Cellular Studies

Abstract

The purpose of this study was to formulate Lactomorphin (MMP2200) in its pure state as spray-dried(SD) powders, and with the excipient Trehalose as co-spray-dried(co-SD) powders; for intranasal and deep lung administration with Dry Powder Inhalers (DPI). Lactomorphin is a glycopeptide which was developed for the control of moderate to severe pain. Particles were rationally designed and produced by advanced spray drying particle engineering in a closed mode from a dilute organic solution. Comprehensive physicochemical characterization using different analytical techniques was carried out to analyze the particle size, particle morphology, particle surface morphology, solid-state transitions, crystallinity/non-crystallinity, and residual water content. The particle chemical composition was confirmed using attenuated total reflectance-Fourier-transform infrared (ATR-FTIR), and Confocal Raman Microscopy (CRM) confirmed the particles’ chemical homogeneity. The solubility and Partition coefficient (LogP) of Lactomorphin were determined by the analytical and computational methodology and revealed the hydrophilicity of Lactomorphin. A thermal degradation study was performed by exposing samples of solid-state Lactomorphin to a high temperature (62 °C) combined with zero relative humidity (RH) and to a high temperature (62 °C) combined with a high RH (75%) to evaluate the stability of Lactomorphin under these two different conditions. The solid-state processed particles exhibited excellent aerosol dispersion performance with an FDA-approved human DPI device to reach lower airways. The cell viability resazurin assay showed that Lactomorphin is safe up to 1000 μg/mL on nasal epithelium cells, lung cells, endothelial, and astrocyte brain cells.

Inhalation Delivery for the Treatment and Prevention of COVID-19 Infection

“…The pulmonary route ( Figure 1 ) is considered a targeted lung delivery since it offers the administration of a drug directly to its site of action, resulting in a rapid onset of activity with smaller administered doses and higher concentrations delivered locally to the lungs’ disease site. Furthermore, minimizing systemic bioavailability reduces the potential incidence of adverse systemic toxicities and avoids the first-pass metabolism in the liver [ 8 , 30 , 31 ].…”

Synthesis, Physicochemical Characterization, In Vitro 2D/3D Human Cell Culture, and In Vitro Aerosol Dispersion Performance of Advanced Spray Dried and Co-Spray Dried Angiotensin (1—7) Peptide and PNA5 with Trehalose as Microparticles/Nanoparticles for Targeted Respiratory Delivery as Dry Powder Inhalers

“…The solubilities of Ang (1-7) and PNA5 were determined by the SFM using conditions similar to previously reported by our group [24] and in [39][40][41][42]. Each compound's excess powder was added to a specific volume of different solvents (purified water, phosphate buffered saline (PBS), normal saline (NS), methanol, and ethanol) in closed, light-protected glass vials.…”

“…There is increasing attention to formulate therapeutic proteins and peptides as Spraydried inhalable powder formulations [23,24]. In this study, our goal was to formulate Ang (1-7) and PNA5 as dry powders suitable to be delivered to the respiratory tract (upper and lower).…”

Non-Invasive Drug Delivery Systems

“…Non-invasive drug delivery research is an active, rich and multidisciplinary research area and this Special Issue aims to present the current state of the art in the field. The contributions in this Special Issue address drug delivery systems for administration through the oral route [ 1 , 2 , 3 , 4 ], respiratory administration [ 5 , 6 ], nose-to-brain delivery [ 7 ] and via the skin [ 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Furthermore, a broad range of drug delivery systems and therapeutics (both small drug molecules and biologics) for non-invasive delivery were investigated and discussed, including nanosystems such as silica nanoparticles [ 15 ].…”

“…Alabsi et al [ 5 ] report on the successful design of spray-dried inhalable dry powders containing the glycopeptide MMP2200 (lactomorphin)—a novel glycopeptide opioid agonist—either alone or in combination with the excipient trehalose for intranasal and deep lung administration. A comprehensive physicochemical characterisation was reported, concluding that the formulations possessed the required properties for respiratory drug delivery as inhaled dry powder aerosols.…”