Inhalable PEGylated Phospholipid Nanocarriers and PEGylated Therapeutics for Respiratory Delivery as Aerosolized Colloidal Dispersions and Dry Powder Inhalers.

Priya Muralidharan,Monica Malapit,Evan Mallory,Don Hayes,Heidi Mansour

doi:10.3390/pharmaceutics6020333

Priya Muralidharan, Monica Malapit + Show 3 more

Open Access

https://doi.org/10.3390/pharmaceutics6020333

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Abstract

Nanomedicine is making groundbreaking achievements in drug delivery. The versatility of nanoparticles has given rise to its use in respiratory delivery that includes inhalation aerosol delivery by the nasal route and the pulmonary route. Due to the unique features of the respiratory route, research in exploring the respiratory route for delivery of poorly absorbed and systemically unstable drugs has been increasing. The respiratory route has been successfully used for the delivery of macromolecules like proteins, peptides, and vaccines, and continues to be examined for use with small molecules, DNA, siRNA, and gene therapy. Phospholipid nanocarriers are an attractive drug delivery system for inhalation aerosol delivery in particular. Protecting these phospholipid nanocarriers from pulmonary immune system attack by surface modification by polyethylene glycol (PEG)ylation, enhancing mucopenetration by PEGylation, and sustaining drug release for controlled drug delivery are some of the advantages of PEGylated liposomal and proliposomal inhalation aerosol delivery. This review discusses the advantages of using PEGylated phospholipid nanocarriers and PEGylated therapeutics for respiratory delivery through the nasal and pulmonary routes as inhalation aerosols.

Highlights

The majority of therapeutic agents are hydrophobic or poorly soluble in water, which is a hurdle in drug formulation as it renders the drug less bioavailable
Based on its biocompatibility and amphiphilicity, PEGylation has been applied in biomedical research to suppress graft rejection and immunogenicity and to prolong circulation time in the blood [19]
This study has shown that the half-life was directly related to the Polyethylene Glycol (PEG) chain length; the PEG

Summary

Introduction

The majority of therapeutic agents are hydrophobic or poorly soluble in water, which is a hurdle in drug formulation as it renders the drug less bioavailable. The steric hindrance created by PEG molecule was larger than the van der Waals force between the lipid particle and protein, protecting the particle from opsonin attack They observed that a small-sized curved surface is less favorable for complement activation, which offers spherical nanoparticles a better chance to evade opsonization [11]. PEG of higher molar mass (20,000–50,000) makes the therapeutic molecule bigger than the size the kidney can filter This property increases the circulation of PEGylated molecule in the blood for a long time, which gives it the opportunity to be used in sustained release pharmaceuticals [6].

PEGylated Drug Delivery

Phospholipid Nanocarriers

Nasal Drug Delivery

Findings

10. Conclusions and Future Directions