Evaluation of the clearance characteristics of various microspheres in the human nose by gamma-scintigraphy.

The nasal cavity possesses many advantages as a site for drug delivery, such as; ease of administration, applicability for long-term treatments and a large surface area for absorption. One important limiting factor for nasal drug delivery is the limited time available for absorption within the nasal cavity due to mucociliary clearance. Several drug delivery systems including different kinds of microspheres have been tried for encapsulation of drugs and increasing the residence time in nasal cavity. In this study the clearance rate of three kinds of microspheres (Alginate, PLGA, and Sephadex) was determined by gamma-scintigraphy with lactose powder being used as negative control. (99m)Tc labeled microspheres were prepared using technetium pertechnetate in the presence of a potent reducing agent, stannus chloride. The labeling procedure was set in a manner that each 3-5 mg of microspheres contained 2 MBq of radioactivity. Labeling efficiency was calculated by paper chromatography using acetone as a mobile phase. Each delivery system containing 2 MBq of activity was administered into right nostril of four healthy volunteers and 1 min static views were repeated each half an hour until 4 h. Clearance rates were compared using two regions of interest (ROIs); the initial site of deposition of particles, and all of the nasopharynx region. The clearance rate of each one of microspheres was calculated after applying the physical decay corrections. The mean labeling efficiencies for Alginate, PLGA, and Sephadex microspheres were calculated as 60%, 59%, and 74%, respectively. The cleared percent of formulations from nasopharynx region after 4 h was determined as follows: PLGA microspheres 48.5 +/- 8.2%; Alginate microspheres 45.0 +/- 0.8%; Sephadex microspheres 63.1 +/- 3.4%; lactose powder 74.5 +/- 4.9%. Alginate and PLGA microspheres showed the lowest clearance rate compared to lactose powder (P < 0.0001 and P < 0.001, respectively), followed by Sephadex microspheres (P < 0.01). The clearance profiles of formulations from deposition ROI and nasopharynx ROI were identical. This study shows that Alginate and PLGA microspheres have the highest mucoadhesion properties and are suitable nasal delivery systems. Futhermore, this study proves that limiting step for the nasal clearance of nasally administered particulate systems is their dislocation from the initial site of deposition, and their following interactions with mucus layer in the rest of the nasal passage does not significantly affect the clearance time.