Microneedle-mediated intradermal nanoparticle delivery: Potential for enhanced local administration of hydrophobic pre-formed photosensitisers.
BACKGROUND
To date, 5-aminolevulinic acid (ALA) has been the most widely used agent in topical photodynamic therapy (PDT). However, owing to the poor penetration of ALA into skin, ALA-PDT is inappropriate for difficult-to-treat deep skin neoplasias, such as nodular basal cell carcinoma. An alternative strategy to ALA-PDT is to use pre-formed photosensitisers, which can be activated at longer wavelengths, facilitating enhanced light penetration into skin. Owing to their relatively high molecular weights and often high lipophilicities, these compounds cannot be effectively administered topically. This study aimed to deliver a model hydrophobic dye, Nile red, into the skin using novel microneedle (MN) technology.


METHODS
Nile red was incorporated into poly-lactide-co-glycolic acid (PLGA) nanoparticles using an emulsion and salting-out process. Polymeric MN arrays were prepared from aqueous blends of the mucoadhesive copolymer Gantrez(®) AN-139 and tailored to contain 1.0mg of Nile red-loaded PLGA nanoparticles. Intradermal delivery of Nile red was determined in vitro.


RESULTS
Uniform 150nm diameter PLGA nanoparticles were prepared containing 3.87μg Nile red / mg of PLGA. Tissue penetration studies using excised porcine skin revealed that high tissue concentrations of Nile red were observed at 1.125mm (382.63ng cm(-3)) following MN delivery.


CONCLUSIONS
For the first time, polymeric microneedles (MN) have been employed to deliver a model lipophilic dye, Nile red, into excised porcine skin. Importantly, this is a one-step delivery strategy for the local delivery of highly hydrophobic agents, which overcomes many of the disadvantages of current delivery strategies.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK. r.donnelly@qub.ac.uk
Ryan F
RF
Donnelly
Desmond I J
DI
Morrow
Francois
F
Fay
Christopher J
CJ
Scott
Sharif
S
Abdelghany
Raghu Raj Thakur
RR
Singh
Martin J
MJ
Garland
A David
AD
Woolfson
D000818:Animals; D005456:Fluorescent Dyes / Q000008:administration & dosage*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D007271:Injections, Intradermal; D019344:Lactic Acid / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles / Q000737:chemistry*; D009339:Needles; D010078:Oxazines / Q000008:administration & dosage*; D010316:Particle Size; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012869:Skin Absorption; D013552:Swine
D005456:Fluorescent Dyes; D010078:Oxazines; D017319:Photosensitizing Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C044808:nile red