Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular
- PMID: 29264927
- PMCID: PMC5874330
- DOI: 10.1177/1091581817741840
Toxicology Evaluation of Drugs Administered via Uncommon Routes: Intranasal, Intraocular, Intrathecal/Intraspinal, and Intra-Articular
Abstract
As the need for nasal, ocular, spinal, and articular therapeutic compounds increases, toxicology assessments of drugs administered via these routes play an important role in human safety. This symposium outlined the local and systemic evaluation to support safety during the development of these drugs in nonclinical models with some case studies. Discussions included selection of appropriate species for the intended route; conducting nonclinical studies that closely mimic the intended use with adequate duration; functional assessment, if deemed necessary; evaluation of local tissues with special histological staining procedure; and evaluations of safety margins based on local and systemic toxicity.
Keywords: analgesics; antispasticity; epidural; granuloma; intra-articular; intracameral; intranasal; intrathecal; intravitreal; local toxicity; safety evaluation; safety margins; spinal cord; toxicity.
Conflict of interest statement
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Figures
![Figure 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5874330/bin/nihms915146f1.gif)
![Figure 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5874330/bin/nihms915146f2.gif)
![Figure 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5874330/bin/nihms915146f3.gif)
![Figure 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5874330/bin/nihms915146f4.gif)
![Figure 5](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5874330/bin/nihms915146f5.gif)
![Figure 6](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5874330/bin/nihms915146f6.gif)
![Figure 7](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5874330/bin/nihms915146f7.gif)
Similar articles
-
General considerations in ocular toxicity risk assessment from the toxicologists' viewpoints.J Toxicol Sci. 2015 Jun;40(3):295-307. doi: 10.2131/jts.40.295. J Toxicol Sci. 2015. PMID: 25972191 Review.
-
Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules.Eur J Pharm Biopharm. 2014 Sep;88(1):8-27. doi: 10.1016/j.ejpb.2014.03.004. Epub 2014 Mar 28. Eur J Pharm Biopharm. 2014. PMID: 24681294 Review.
-
Nasal and buccal drug delivery: management forum conference.Ther Deliv. 2012 Jul;3(7):819-22. doi: 10.4155/tde.12.60. Ther Deliv. 2012. PMID: 22900464
-
Nonclinical safety of ziconotide: an intrathecal analgesic of a new pharmaceutical class.Int J Toxicol. 2007 Sep-Oct;26(5):411-21. doi: 10.1080/10915810701582970. Int J Toxicol. 2007. PMID: 17963128
-
Best practices for managing quality and safety of foreign particles in orally inhaled and nasal drug products, and an evaluation of clinical relevance.Pharm Res. 2007 Mar;24(3):471-9. doi: 10.1007/s11095-006-9172-5. Pharm Res. 2007. PMID: 17252189 No abstract available.
Cited by
-
Unraveling the path to osteoarthritis management: targeting chondrocyte apoptosis for therapeutic intervention.Front Cell Dev Biol. 2024 May 17;12:1347126. doi: 10.3389/fcell.2024.1347126. eCollection 2024. Front Cell Dev Biol. 2024. PMID: 38827524 Free PMC article. Review.
-
The In Vivo Chondrotoxicity of Single Intra-articular Injection of Local Anesthetic in Rat Cartilage.Cureus. 2024 Jan 28;16(1):e53103. doi: 10.7759/cureus.53103. eCollection 2024 Jan. Cureus. 2024. PMID: 38414680 Free PMC article.
-
The Efficacy of a Human-Ready miniMECP2 Gene Therapy in a Pre-Clinical Model of Rett Syndrome.Genes (Basel). 2023 Dec 24;15(1):31. doi: 10.3390/genes15010031. Genes (Basel). 2023. PMID: 38254921 Free PMC article.
-
Rutaecarpine ameliorates osteoarthritis by inhibiting PI3K/AKT/NF‑κB and MAPK signalling transduction through integrin αVβ3.Int J Mol Med. 2023 Oct;52(4):97. doi: 10.3892/ijmm.2023.5300. Epub 2023 Sep 1. Int J Mol Med. 2023. PMID: 37654229 Free PMC article.
-
Ozone Therapy versus Hyaluronic Acid Injections for Pain Relief in Patients with Knee Osteoarthritis: Preliminary Findings on Molecular and Clinical Outcomes from a Randomized Controlled Trial.Int J Mol Sci. 2023 May 15;24(10):8788. doi: 10.3390/ijms24108788. Int J Mol Sci. 2023. PMID: 37240135 Free PMC article. Clinical Trial.
References
-
- Illum L. Nasal clearance in health and disease. J Aerosol Med. 2006 Spring;19(1):92–9. - PubMed
-
- Grassin-Delyle S, Buenestado A, Naline E, Faisy C, Blouquit-Laye S, Couderc LJ, Le Guen M, Fischler M, Devillier P. Intranasal drug delivery: an efficient and non-invasive route for systemic administration: focus on opioids. Pharmacol Ther. 2012 Jun;134(3):366–79. Reed (1993) - PubMed
-
- Fortuna A, Alves G, Serralheiro A, Sousa J, Falcão A. Intranasal delivery of systemic-acting drugs: small-molecules and biomacromolecules. Eur J Pharm Biopharm. 2014 Sep;88(1):8–27. - PubMed
-
- Mittal D, Ali A, Md S, Baboota S, Sahni JK, Ali J. Insights into direct nose to brain delivery: current status and future perspective. Drug Deliv. 2014 Mar;21(2):75–86. - PubMed
-
- Pires A, Fortuna A, Alves G, Falcão A. Intranasal drug delivery: how, why and what for? J Pharm Pharm Sci. 2009;12(3):288–311. Review. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials