Dieter Scherer

Influence of enzymes on the stability of polybutylcyanoacrylate nanoparticles

Abstract The influence of three different enzymes (amylase, pepsin and esterase) on the stability of polybutylcyanoacrylate (PBCA) nanoparticles was studied. The study was performed as an in vitro investigation using side-by-side diffusion cells. A suspension of 14C-labelled PBCA nanoparticles was placed into the donor chamber of the diffusion cell and incubated with the above-mentioned enzymes. Esterase caused a highly significant degradation of the nanoparticles that was proportional to the amount of the enzyme put into the donor chamber. Amylase and pepsin had no significant effect on the stability of the PBCA nanoparticles.

In Vitro Permeability of PBCA Nanoparticles through Porcine Small Intestine

Peroral nanoparticle-mediated drug absorption was studied using a laser scanning confocal microscope. Additional diffusion studies in side-by-side diffusion cells with radiolabelled polybutylcyanoacrylate (PBCA) nanoparticles were carried out to confirm the results of this study. Fluorescence-labelled PBCA nanoparticles were incubated in vitro in the lumen of freshly excised intestine. Computer-aided optical sectioning of thick samples with dramatically improved resolution and the possibility of rejecting out-of-focus noise enabled tracking of the fluorescence-labelled PBCA nanoparticles in the intestinal tissue after incubation of the particles in freshly excised porcine small intestine. The results of this study suggest that the nanoparticles are absorbed by the surface of the gut wall, creating a high concentration gradient, thereby enhancing the absorption of drugs that may be loaded to the nanoparticles. A significant amount of particles was found in hot (very fluorescent) spots that were assumed to be Peyers patches. No particles, however, traversed the entire gut wall over a period of 2 to 4 h. These results were confirmed by the diffusion study. No radioactivity permeated through Peyers-patch-free intestine within 4 h, whereas the amount of radioactivity that was transported through intestine with Peyers patches during this time was 1.1% of the total amount in the donor chamber.

Semifluorinated alkane based systems for enhanced corneal penetration of poorly soluble drugs

Semifluorinated alkanes (SFAs) are amphiphilic liquids that can dissolve hydrophobic drugs to form clear solutions. This study evaluated the potential of two SFAs to act as vehicle for topical ocular drug delivery. After confirming ocular safety, an ex vivo corneal penetration model was developed to determine drug distribution and corneal bioavailability. Hydrophobic dye distribution in the different corneal layers was visualised under a confocal microscope. Corneal bioavailability of cyclosporine A (CsA) dissolved in perfluorobutylpentane (F4H5) or perfluorohexyloctane (F6H8) was compared to commercially available CsA ophthalmic emulsions, Restasis® and Ikervis®. Precorneal residence of the four test vehicles containing the hydrophobic dye was also compared using an ex vivo corneal tissue model. Preferential accumulation of the hydrophobic dye in the corneal epithelium was observed with higher amounts detectable when delivered via the SFAs compared to Restasis or Ikervis. A significant improvement in corneal CsA penetration was observed after application of a single dose of 0.05% CsA in F4H5 and F6H8 when compared to Restasis with the area under curve over 4 h (AUC(0-4h)) being at least 8-fold greater for both SFAs (p < .0001). Moreover, the AUC(0-4h) of 0.1% CsA in F4H5 was almost 5-fold greater than Ikervis (p < .0001). Finally, the precorneal residence time of both SFA solutions was significantly longer than that of the commercial emulsions with the AUC(0-60min) being 2- to 11-fold greater. This study demonstrated that SFAs can significantly improve the local bioavailability of hydrophobic drugs by increasing corneal penetration as well as prolonging precorneal residence. They therefore offer a promising new platform for topical drug delivery to the eye.