Improved Flux of Levodopa via Direct Deposition of Solid Microparticles on Nasal Tissue

Abstract

Epithelial flux and permeability across bovine olfactory tissue were compared when levodopa (L-DOPA) was loaded in different physical states. Aqueous solution of L-DOPA was prepared in Krebs-Ringer buffer (KRB), at a concentration (0.75 mg/mL) verified to be less than the saturation solubility at both 25 and 37°C. Sodium metabisulfite was added to solution to minimize L-DOPA oxidation; chemical stability of aqueous L-DOPA was evaluated using HPLC-UV. Solid-state characterization of unprocessed, dry, crystalline L-DOPA powder was performed using TGA, DSC, PXRD, and optical microscopy to ensure that preparation of L-DOPA microparticles used for diffusion experiments did not elicit a phase change. Measurements of in vitro flux were made for all preparations, using freshly excised bovine olfactory mucosal membrane. Samples obtained from transport studies were analyzed by HPLC-UV. Tissue viability was measured before and after experiments using transdermal epithelial electrical resistance (TEER). The average steady-state flux (J ) of L-DOPA from solid microparticles directly deposited on nasal epithelial tissue was 6.08 ± 0.69 μg/cm/min, approximately three times greater than the J measured for L-DOPA from solution (2.13 ± 0.97 μg/cm/min). The average apparent permeability coefficient (P ) of L-DOPA was calculated to be 4.73 × 10 cm/s. These findings suggest that nasal delivery of L-DOPA by administration of solid microparticles not only benefits from improved chemical and microbiological stability by avoiding the use of aqueous formulation vehicle but also does not compromise cumulative mass transport across the olfactory membrane.

How to characterize a nasal product. The state of the art of in vitro and ex vivo specific methods

“…For instance, the olfactory mucosa can be easily differentiated from the pink respiratory mucosa due to its yellowish aspect caused by the presence of a coloured pigment (i.e. carotenoid) (Vasa et al, 2017;Moulton, 1971;Graziadei, 1971;Amoore et al, 1971). Additional protocol steps have been proposed after tissue collection, such as the step of delipidation with organic solvents (chloroform, methanol) .…”

Investigation of the Absorption of Nanosized lamotrigine Containing Nasal Powder via the Nasal Cavity

“…Accordingly, the nose can be a great alternative administration route in the therapy of CNS diseases or when the target is in the CNS (e.g., brain tumors). Thus, in recent years, researchers have made some efforts to formulate drug delivery systems for the treatment of schizophrenia [11,12], epilepsy [13,14], Alzheimer's disease [15][16][17][18], Parkinson's disease [19,20], migraine [21], vaccination [22,23], and brain tumor [24]. In some cases the aim was to formulate nanosystems, that may be advantageous due to reduced particle size and increased particle surface, which can affect the absorption positively [25].…”

Evaluatıon Of Release Of L-DOPA From PLGA Nanopartıcles Wıth Dıfferent In Vıtro Relase Methods By An Optımızed HPLC Method

“…PD's conventional treatment is based on replacing dopamine in living neurons by administering L-Dopa which is the most commonly used dopamine precursor. Conventional therapy has some disadvantages such as fluctuant plasma levels of L-Dopa because of irregular gastric emptying and intermittent oral intake (3), poor relative bioavailability (∼5-15%),and less than 1% of the administered dose reaching to the brain (4)(5)(6)(7).…”