Ex Vivo Permeation of Carprofen Vehiculated by PLGA Nanoparticles through Porcine Mucous Membranes and Ophthalmic Tissues

Abstract

(1) Background: Carprofen (CP), 2-(6-chlorocarbazole) propionic acid, is used as an anti-inflammatory, analgesic and anti-pyretic agent and it belongs to the family of non-steroidal anti-inflammatory drugs (NSAIDs). CP has some adverse reactions in systemic administration; for this reason, topical administration with CP nanoparticles (CP-NPs) can be an optimal alternative. The main objective of this work is the investigation of ex vivo permeation of CP through different types of porcine mucous membranes (buccal, sublingual and vaginal) and ophthalmic tissues (cornea, sclera and conjunctiva) to compare the influence of CP-NPs formulation over a CP solution (CP-Solution). (2) Methods: The ex vivo permeation profiles were evaluated using Franz diffusion cells. Furthermore, in vivo studies were performed to verify that the formulations did not affect the cell structure and to establish the amount retained (Qr) in the tissues. (3) Results: Permeation of CP-NPs is more effective in terms of drug retention in almost all tissues (with the exception of sclera and sublingual). In vivo studies show that neither of the two formulations affects tissue structure, so both formulations are safe. (4) Conclusions: It was concluded that CP-NPs may be a useful tool for the topical treatment of local inflammation in veterinary and human medicine.

Keywords: NSAIDs; anti-inflammatory; carprofen; drug delivery system; nanoparticles; solution; veterinary diseases.

Figure 1

Chromatogram of the Carprofen (CP) validation line at concentration 100 µg/mL.

Figure 2

Chromatogram of CP nanoparticles (CP-NPs) in sclera at 6 h.

Figure 3

Chromatogram of CP-NPs in cornea at 6 h.

Figure 4

Chromatogram of CP-NPs in conjunctiva at 6 h.

Figure 5

Chromatogram of CP-NPs in buccal mucous at 6 h.

Figure 6

Chromatogram of CP-NPs in sublingual mucous at 6 h.

Figure 7

Chromatogram of CP-NPs in vaginal mucous at 6 h.

Figure 8

Photo 1: Histological image of untreated buccal mucous observed at 400×; Photo 2: Histological image of buccal mucous treated with CP-Solution observed at 400×; Photo 3: Histological image of buccal mucous treated with CP-NPs observed at 400×. (A) Stratified flat keratinized epithelium; (B) own laminate. (C) dermal papilla; (D) basal layer and (E) buccal mucous.

Figure 9

Photo 4: Histological image of untreated sublingual mucous observed at 400×; Photo 5: Histological image of sublingual mucous treated with CP-Solution observed at 400×; Photo 6: Histological image of sublingual mucous treated with CP-NPs observed at 400×. (A) Stratified flat keratinized epithelium; (B) own laminate. (C) muscle and (D) collagen fibers.

Figure 10

Photo 7: Histological image of untreated vaginal mucous observed at 400×; Photo 8: Histological image of vaginal mucous treated with CP-Solution observed at 400×; Photo 9: Histological image of vaginal mucous treated with CP-NPs observed at 400×. (A) Stratified flat keratinized epithelium; (B) own laminate.

Figure 11

Photo 10: Histological image of untreated cornea observed at 400×; Photo 11: Histological image of cornea treated with CP-Solution observed at 400×; Photo 12: Histological image of cornea treated with CP-NPs observed at 400×. (A) Stratified flat keratinized epithelium; (B) own laminate. (C) Bowman’s membrane.

Figure 12

Photo 13: Histological image of untreated conjunctive mucous observed at 400×; Photo 14: Histological image of conjunctive mucous treated with CP-Solution observed at 400×; Photo 15: Histological image of conjunctive mucous treated with CP-NPs observed at 400×. (A) Stratified flat keratinized epithelium; (B) own laminate. (C) oil gland and (D) hair Follicle.

Figure 13

Photo 16: Histological image of untreated sclera observed at 400×; Photo 17: Histological image of sclera treated with CP-Solution observed at 400×; Photo 18: Histological image of sclera treated with CP-NPs observed at 400×. A: Stratified flat keratinized episclera; (B) stroma (collagen fibers). (C) fusca laminate (blood vessels).