Abstract
The objective of the present study was to develop n-propyl gallate-loaded solid lipid nanoparticles (PG-SLNs) in a hydrogel (HG) formulation using Transcutol-P (TC-P) as a permeation enhancer. Modified solvent injection technique was applied to produce optimized PG-SLNs via the Quality by Design approach and central composite design. The in vitro mucoadhesion, scavenging activity, drug release, permeation studies of PG from PG-SLNs-loaded HG were evaluated under simulated nasal conditions. Compared with in vitro release behavior of PG from SLNs, the drug release from the PG-SLNs-loaded HG showed a lower burst effect and sustained release profile. The cumulative permeation of PG from PG-SLNs-loaded HG with TC-P was 600 μg/cm2 within 60 min, which is 3–60-fold higher than PG-SLNs and native PG, respectively. Raman mapping showed that the distribution of PG-SLNs was more concentrated in HG having lower concentrations of hyaluronic acid. The scavenging assay demonstrated increased antioxidant activity at higher concentrations of HG. Due to enhanced stability and mucoadhesive properties, the developed HG-based SLNs can improve nasal absorption by increasing residence time on nasal mucosa. This study provides in vitro proof of the potential of combining the advantages of SLNs and HG for the intranasal delivery of antioxidants.
Highlights
In the past few years, the intranasal administration route has gained considerable interest since it provides a non-invasive method to bypass the blood–brain barrier (BBB).Most regions in the central nervous system (CNS) can be directly reached along the olfactory and trigeminal nerves by intranasal administration of drugs
SLN embedded in a HG formulation that is able to enter the central nervous system via the nose-to-brain pathway as a patient adherence improving drug delivery pathway offering direct transport to the CNS
SLN embedded in a HG formulation that is able to enter the central nervous system3 of via the nose-to-brain pathway as a patient adherence improving drug delivery pathway offering direct transport to the CNS
Summary
Most regions in the central nervous system (CNS) can be directly reached along the olfactory and trigeminal nerves by intranasal administration of drugs. Limited brain uptake can be achieved in numerous intranasally applied compounds from conventional formulations, including chemotherapeutics and antineoplastic agents, due to their low permeability, enzymatic degradation and rapid elimination by mucociliary clearance from the nasal cavity [5,6,7]. To hurdle these obstacles, the application of nano drug delivery systems can be a suitable tool
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