Spray-Dried Inhalable Powder Formulations of Therapeutic Proteins and Peptides

Eedara, Basanth Babu; Alabsi, Wafaa; Encinas-Basurto, David; Polt, Robin; Mansour, Heidi M.

doi:10.1208/s12249-021-02043-5

Cited by 28 publications

(13 citation statements)

References 80 publications

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“…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 ].…”

Section: Inhalational Drug Administration—an Overviewmentioning

confidence: 99%

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

et al. 2021

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Coronavirus disease-2019 (COVID-19) is caused by coronavirus-2 (SARS-CoV-2) and has produced a global pandemic. As of 22 June 2021, 178 million people have been affected worldwide, and 3.87 million people have died from COVID-19. According to the Centers for Disease Control and Prevention (CDC) of the United States, COVID-19 virus is primarily transmitted between people through respiratory droplets and contact routes. Since the location of initial infection and disease progression is primarily through the lungs, the inhalation delivery of drugs directly to the lungs may be the most appropriate route of administration for treating COVID-19. This review article aims to present possible inhalation therapeutics and vaccines for the treatment of COVID-19 symptoms. This review covers the comparison between SARS-CoV-2 and other coronaviruses such as SARS-CoV/MERS, inhalation therapeutics for the treatment of COVID-19 symptoms, and vaccines for preventing infection, as well as the current clinical status of inhaled therapeutics and vaccines.

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Section: Inhalational Drug Administration—an Overviewmentioning

confidence: 99%

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

et al. 2021

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“…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).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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The peptide hormone Angiotensin (1—7), Ang (1—7) or (Asp-Arg-Val-Tyr-Ile-His-Pro), is an essential component of the renin–angiotensin system (RAS) peripherally and is an agonist of the Mas receptor centrally. Activation of this receptor in the CNS stimulates various biological activities that make the Ang (1—7)/MAS axis a novel therapeutic approach for the treatment of many diseases. The related O-linked glycopeptide, Asp-Arg-Val-Tyr-Ile-His-Ser-(O-β-D-Glc)-amide (PNA5), is a biousian revision of the native peptide hormone Ang (1—7) and shows enhanced stability in vivo and greater levels of brain penetration. We have synthesized the native Ang (1—7) peptide and the glycopeptide, PNA5, and have formulated them for targeted respiratory delivery as inhalable dry powders. Solid phase peptide synthesis (SPPS) successfully produced Ang (1—7) and PNA5. Measurements of solubility and lipophilicity of raw Ang (1—7) and raw PNA5 using experimental and computational approaches confirmed that both the peptide and glycopeptide have high-water solubility and are amphipathic. Advanced organic solution spray drying was used to engineer the particles and produce spray-dried powders (SD) of both the peptide and the glycopeptide, as well as co-spray-dried powders (co-SD) with the non-reducing sugar and pharmaceutical excipient, trehalose. The native peptide, glycopeptide, SD, and co-SD powders were comprehensively characterized, and exhibited distinct glass transitions (Tg) consistent with the amorphous glassy state formation with Tgs that are compatible with use in vivo. The homogeneous particles displayed small sizes in the nanometer size range and low residual water content in the solid-state. Excellent aerosol dispersion performance with a human DPI device was demonstrated. In vitro human cell viability assays showed that Ang (1—7) and PNA5 are biocompatible and safe for different human respiratory and brain cells.

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“…More recent efforts have focused on co-administration of protease inhibitors or permeability modifiers with specialized carriers with only minor improvements in bioavailability (Bao et al, 2021). Other efforts have ignored the intestine altogether and explored protein and peptide delivery through transdermal patches containing microneedles (Aich et al, 2021) or inhalation of lyophilized therapeutic protein powders (Eedara et al, 2021). However, patients prefer the simplicity and painless delivery of oral medications and capsules are by far the most acceptable, and safest, form of oral drug administration to patients (Kaur et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Transenteric delivery of antibodies via an orally ingestible robotic pill yields high bioavailability comparable to parenteral administration in awake canines

Yamaguchi

Dam²,

Dhalla³

et al. 2022

Front. Drug. Deliv.

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Biotherapeutics such as peptides and antibodies are highly efficacious clinically but, unlike conventional medications, cannot be administered orally as they get digested and inactivated. Thus, biotherapeutics require parenteral routes for delivery, such as intravenous, intramuscular or subcutaneous administration. However, these delivery methods have limitations such as poor patient compliance or may require clinical supervision compared to oral therapies. We explored whether a novel, orally administered transenteric delivery system (Robotic Pill) could provide equivalent bioavailability to parenterally administered drugs. Utilizing an awake canine model, we demonstrated that orally administered Robotic Pills containing either human IgG or an anti-cytokine monoclonal antibody directed against either TNFα or interleukin-17A yielded bioavailability equivalent to parenterally administered controls. The ability to achieve clinically relevant blood levels of biotherapeutics via any orally administered preparation represents an important advance in drug delivery.

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Spray-Dried Inhalable Powder Formulations of Therapeutic Proteins and Peptides

Cited by 28 publications

References 80 publications

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

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

Transenteric delivery of antibodies via an orally ingestible robotic pill yields high bioavailability comparable to parenteral administration in awake canines

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