title: Influence of solution viscosity and injection protocol on distribution patterns of jet injectors: application to photodynamic tumour targeting.
abstract: Photodynamic therapy of deep or nodular skin tumours is currently limited by the poor tissue penetration of the porphyrin precursor 5-aminolevulinic acid (ALA) and preformed photosensitisers. In this study, we investigated the potential of jet injection to deliver both ALA and a preformed photosensitiser (meso-tetra (N-methyl-4-pyridyl) porphine tetra tosylate, TMP) into a defined volume of skin. Initial studies using a model hydrogel showed that as standoff distance is increased, injection depth decreases. As the ejected volume is increased, injection depth increases. It was also shown, for the first time, that, as injection solution viscosity was increased, for a given injection setting and standoff distance, both total depth of jet penetration, L(t), and depth at which the maximum width of the penetration pattern occurred, L(m), decreased progressively. For a standoff distance of zero, the maximum width of the penetration pattern, L(w), increased progressively with increasing viscosity at each of the injection settings. Conversely, when the standoff distance was 2.5 mm, L(w) decreased progressively with increasing viscosity. Studies with neonate porcine skin revealed that an injection protocol comprising an 8.98 mPas solution, an arbitrary injection setting of 8 and a standoff distance of zero was capable of delivering photosensitisers to a volume of tissue (L(t) of 2.91 mm, L(m) of 2.14 mm, L(w) of 5.10 mm) comparable to that occupied by a typical nodular basal cell carcinoma. Both ALA and TMP were successfully delivered using jet injection, with peak tissue concentrations (67.3 mg cm(-3) and 5.6 mg cm(-3), respectively) achieved at a depth of around 1.0mm and substantial reductions in drug concentration seen at depths below 3.0 mm. Consequently, jet injection may be suitable for selective targeting of ALA or preformed photosensitisers to skin tumours.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. r.donnelly@qub.ac.uk
authors.forename: Ryan F
authors.initials: RF
authors.lastname: Donnelly
authors.forename: Desmond I J
authors.initials: DI
authors.lastname: Morrow
authors.forename: Paul A
authors.initials: PA
authors.lastname: McCarron
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Garland
authors.forename: A David
authors.initials: AD
authors.lastname: Woolfson
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage; D000818:Animals; D000831:Animals, Newborn; D005470:Fluorometry; D020100:Hydrogels; D007277:Injections, Jet / Q000379:methods*; D010778:Photochemotherapy / Q000379:methods*; D011142:Polyvinyl Alcohol; D011166:Porphyrins / Q000008:administration & dosage; D012878:Skin Neoplasms / Q000188:drug therapy*; D034421:Sus scrofa; D014783:Viscosity
chemical_list: D020100:Hydrogels; D011166:Porphyrins; C021096:tetra(4-N-methylpyridyl)porphine; D000622:Aminolevulinic Acid; D011142:Polyvinyl Alcohol