Speaker
Abstract
Background: Intranasal drug delivery offers a promising non-invasive route for brain targeting by bypassing the blood–brain barrier and reducing systemic exposure. Nanovesicular systems enhance nasal mucosal penetration for central nervous system drug delivery; however, adequate drug entrapment remains a key formulation challenge. Polyvinyl alcohol (PVA) is a well-established stabilizer and surface modifier, yet its role at low concentrations in solvent-free nanovesicular systems for intranasal brain delivery has not been clearly defined.
Objective: This study investigated whether low-concentration PVA could improve drug retention and intranasal brain-delivery performance of a solvent-free risperidone nanovesicular system.
Method: The uncoated formulation (PVA0) contained risperidone, Span 60, cholesterol, and dicetyl phosphate (24, 50, 45, and 18 mg, respectively) in 10 mL phosphate-buffered saline (pH 7.4). PVA was screened at 2.5–30 mg/mL. Formulations were prepared by an aqueous, organic-solvent-free sequential probe–bath–probe sonication method and refrigerated for 24 h, offering a greener preparation approach. The selected formulation (PVA1; 2.5 mg/mL) was characterized for vesicle size, PDI, zeta potential, entrapment efficiency (EE), morphology, release, FTIR, refrigerated stability, ex vivo nasal penetration, pharmacodynamic activity, qualitative in vivo distribution, and 24-h L929 MTT cell compatibility.
Results: PVA1 exhibited a mean vesicle size of 212.77 ± 32.37 nm, PDI of 0.27 ± 0.04, zeta potential of −27.76 ± 6.12 mV, and EE of 70.95 ± 5.02%. Relative to PVA0, PVA incorporation raised EE from 50.90 ± 0.50% to 70.95 ± 5.02% (P < 0.01)—an absolute gain of 20.05 percentage points—without a significant size increase. Higher PVA concentrations progressively increased size and PDI, producing visible physical instability. PVA1 retained bilayer vesicular morphology, demonstrated biphasic Fickian release under dialysis conditions, and showed no major FTIR-detectable chemical incompatibility. Curcumin-labelled PVA1 penetrated sheep nasal mucosa ex vivo. In ketamine-treated rats, intranasal PVA1 produced open-field responses comparable to intravenous risperidone at 30 min (P = 0.9999 for time in center; P = 0.9996 for crossing frequency). Coumarin-6 imaging showed stronger head-region fluorescence after intranasal dosing and lower fluorescence in systemic organs than after intravenous dosing. The MTT assay demonstrated 89–116% relative cell activity at risperidone-equivalent concentrations of 28–108 µg/mL.
Conclusion: A PVA concentration of 2.5 mg/mL was identified as a practical coating level that substantially improves risperidone entrapment, preserves vesicle integrity, and supports intranasal delivery and brain-targeting potential, with preliminary cell-compatibility evidence supporting its safety profile.
Keywords: risperidone; polyvinyl alcohol; nanovesicles; intranasal delivery; brain targeting; confocal microscopy; biodistribution
| Intend to be published in the IJPS ? | Yes |
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| Has the manuscript been published | not published |
