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Carprofen Permeation Test through Porcine Ex Vivo Mucous Membranes and Ophthalmic Tissues for Tolerability Assessments: Validation and Histological Study.

ABSTRACT: Carprofen (CP), a non-steroidal anti-inflammatory drug (NSAID), is profusely used in veterinary medicine for its analgesic and anti-inflammatory activity. Some undesirable effects are associated with its systemic administration. Alternative local routes are especially useful to facilitate its administration in animals. The main aim of this paper is to validate the suitability of ex vivo permeation experiments of CP with porcine mucous membranes (buccal, sublingual and vaginal) and ophthalmic tissues (cornea, sclera and conjunctiva) intended to be representative of naïve in vivo conditions. Chromatographic analysis of CP in membrane-permeated samples and drug-retained have been validated following standard bioanalytical guidelines. Then, recovery levels of drugs in tissue samples were assessed with aqueous phosphate buffered saline (PBS) buffer to preserve the histological integrity. Finally, as a proof of concept, a series of CP permeation tests in vertical Franz diffusion cells has been performed to evaluate permeation flux and permeability constants in all tissues, followed by a histological study for critical evaluation. Furthermore, synthetic tissue retention-like samples were prepared to verify the value of this experimental study. Results show linear relationships with good determination coefficient (R² > 0.998 and R² > 0.999) in the range of 0.78 to 6.25 mg/mL and 3.125 mg/mL to 100 mg/mL, respectively. Low limits of quantification around 0.40 µg/mL were allowed to follow permeation levels until a minimum of 0.40% of the locally-applied dose. This method showed a good accuracy and precision with values lower than 2%. After the recovery technique, reproducible values below 30% were achieved in all tissues, suggesting it is a non-damaging method with low efficiency that requires the use of further solvents to enhance the extraction percentages. After permeation and histology tests, no relevant peak interferences were detected, and no cell or tissue damage was found in any tissue. In conclusion, results demonstrate the suitability of this test to quantify the distribution of CP with good histological tolerability.

SUBMITTER: Gomez-Segura L

PROVIDER: S-EPMC7711503 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Carprofen Permeation Test through Porcine Ex Vivo Mucous Membranes and Ophthalmic Tissues for Tolerability Assessments: Validation and Histological Study.

Gómez-Segura Lidia L Parra Alexander A Calpena Ana C AC Gimeno Álvaro Á Boix-Montañes Antonio A

Veterinary sciences 20201010 4

Carprofen (CP), a non-steroidal anti-inflammatory drug (NSAID), is profusely used in veterinary medicine for its analgesic and anti-inflammatory activity. Some undesirable effects are associated with its systemic administration. Alternative local routes are especially useful to facilitate its administration in animals. The main aim of this paper is to validate the suitability of ex vivo permeation experiments of CP with porcine mucous membranes (buccal, sublingual and vaginal) and ophthalmic tis ...[more]

PMID: 33050372

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Project description:BACKGROUND:During several anesthesiological procedures, needles are inserted through the skin of a patient to target nerves. In most cases, the needle traverses several tissues-skin, subcutaneous adipose tissue, muscles, nerves, and blood vessels-to reach the target nerve. A clear identification of the target nerve can improve the success of the nerve block and reduce the rate of complications. This may be accomplished with diffuse reflectance spectroscopy (DRS) which can provide a quantitative measure of the tissue composition. The goal of the current study was to further explore the morphological, biological, chemical, and optical characteristics of the tissues encountered during needle insertion to improve future DRS classification algorithms. METHODS:To compare characteristics of nerve tissue (sciatic nerve) and adipose tissues, the following techniques were used: histology, DRS, absorption spectrophotometry, high-resolution magic-angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy, and solution 2D 13 C-1 H heteronuclear single-quantum coherence spectroscopy. Tissues from five human freshly frozen cadavers were examined. RESULTS:Histology clearly highlights a higher density of cellular nuclei, collagen, and cytoplasm in fascicular nerve tissue (IFAS). IFAS showed lower absorption of light around 1200 nm and 1750 nm, higher absorption around 1500 nm and 2000 nm, and a shift in the peak observed around 1000 nm. DRS measurements showed a higher water percentage and collagen concentration in IFAS and a lower fat percentage compared to all other tissues. The scattering parameter (b) was highest in IFAS. The HR-MAS NMR data showed three extra chemical peak shifts in IFAS tissue. CONCLUSION:Collagen, water, and cellular nuclei concentration are clearly different between nerve fascicular tissue and other adipose tissue and explain some of the differences observed in the optical absorption, DRS, and HR-NMR spectra of these tissues. Some differences observed between fascicular nerve tissue and adipose tissues cannot yet be explained but may be helpful in improving the discriminatory capabilities of DRS in anesthesiology procedures. Lasers Surg. Med. 50:948-960, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Dataset Information

Carprofen Permeation Test through Porcine Ex Vivo Mucous Membranes and Ophthalmic Tissues for Tolerability Assessments: Validation and Histological Study.

Publications

Carprofen Permeation Test through Porcine Ex Vivo Mucous Membranes and Ophthalmic Tissues for Tolerability Assessments: Validation and Histological Study.

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