Nasal delivery of nanosuspension-based mucoadhesive formulation with improved bioavailability of loratadine: Preparation, characterization, and in vivo evaluation

Abstract

The unique requirements of poorly water-soluble drug delivery have driven a great deal of research into new formulations and routes of administration. This study investigates the use of nanosuspensions for solubility enhancement and drug delivery. Simple methods were used to prepare nasal formulations of loratadine based on nanosuspension pre-dispersion with sodium hyaluronate as a mucoadhesive agent. The nanosuspension was prepared by antisolvent precipitation method followed by ultrasonication and characterized for particle size, polydispersity index, zeta potential, morphology, and structure. Moreover, the nasal formulations were characterized for drug loading, pH, particle size, viscosity, bioadhesive viscosity parameter, and were evaluated for in vitro dissolution and diffusion, in addition to in vivo studies in a rat model. Loratadine nanosuspension displayed a particle size of 311 nm, a polydispersity index of 0.16, and zeta potential of -22.05 mV. The nanosuspension preserved the crystalline status of the raw drug. The addition of sodium hyaluronate exhibited an increase in the mean particle size and zeta potential of the nanoparticles. The nasal formulations showed enhanced bioadhesive properties compared to the unprocessed loratadine in the reference samples. The nanosuspension based-formulation that contained 5 mg mL −1 sodium hyaluronate and 2.5 mg mL −1 loratadine (NF4) showed a significant enhancement of flux and permeability coefficient through a synthetic membrane. NF4 exhibited 24.73 µg cm −2 h −1 and 0.082 cm h −1 , while the reference sample showed 1.49 µg cm −2 h −1 and 0.017 cm h −1 , for the flux and the permeability coefficient, respectively. Nasal administration of NF4 showed a bioavailability of 5.54-fold relative to the oral administration. The results obtained in this study indicate the potential of the nasal route and the nanosuspension for loratadine delivery. The relative bioavailability of NF4 was 1.84-fold compared to unprocessed loratadine in the reference sample. Therefore, the nanosized loratadine could be suggested as a practical and simple nanosystem for the intranasal delivery with improved bioavailability.

Antiviral Potential of Nanoparticles—Can Nanoparticles Fight Against Coronaviruses?

“…The intranasal delivery system has been evaluated for vaccination against respiratory viruses such as influenza and CoVs [ 176 , 177 ]. Nanoparticle-Mediated delivery systems have the following benefits—free from enzyme degradation; long-term existence, release and retention within the system; amicable co-delivery with adjuvants; specific targeting of cells through receptor-ligand interactions; and potentiation of the immune system [ 178 , 179 ].…”

Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19

“…Mucoadhesive polymers such as hydroxypropyl methylcellulose 15,000 (HPMC K15M), carbopol 974P and sodium alginate were used in a mixture to increase the residence time of formulation at site of action. 12,13 In this study, COVID-19 patients treated with an ivermectin mucoadhesive nanosuspension nasal spray showed shorter duration of fever, dyspnea, cough, and anosmia but not GIT symptoms duration. Additionally, the findings of the current study revealed that patients with COVID-19 treated with ivermectin showed more significant reduction in measured hematological and biochemical parameters towards normal values with rapid viral clearance as evidenced by conversion of nasopharyngeal swab to negative.…”

“…Saindane et al incorporated a carvedilol-containing nanosuspension into in situ gel, 40 and Alshweiat et al prepared a loratadine-based nasal nanosuspension to improve bioavailability. 12 SARS-CoV-2 invades the oropharynx and nasopharynx, from which it transmits even before any signs appear. The first symptoms (odynophagia, anosmia, dry cough, fever) and lung parenchyma colonization occur when the virus replicates in this region.…”

“…Mucoadhesive polymers such as hydroxypropyl methylcellulose 15,000 (HPMC K15M), carbopol 974P and sodium alginate were used in a mixture to increase the residence time of formulation at site of action. 12 , 13 …”

“… 11 Ivermectin is proved to limit infection caused by some Ribonucleic Acid (RNA) viruses such as West Nile viruses, influenza and dengue virus. 12 It is reported that ivermectin inhibits the replication of SARS-CoV-2 in vitro , and causes reduction about 5000-fold in SARS-CoV-2 viral RNA at 48 hours. 13 In addition, the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein to the human cell membrane may be hindered by ivermectin docking.…”