title: Improved in vivo delivery of m-THPC via pegylated liposomes for use in photodynamic therapy.
abstract: Pegylated liposomal nanocarriers have been developed with the aim of achieving improved uptake of the clinical PDT photosensitiser, m-THPC, into target tissues through increased circulation time and bioavailability. This study investigates the biodistribution and PDT efficacy of m-THPC in its standard formulation (Foscan®) compared to m-THPC incorporated in liposomes with different degrees of pegylation (FosPEG 2% and FosPEG 8%), following i.v. administration to normal and tumour bearing rats. The plasma pharmacokinetics were described using a three compartmental analysis and gave elimination half lives of 90 h, 99 h and 138 h for Foscan®, FosPEG 2% and 8% respectively. The accumulation of m-THPC in tumour and normal tissues, including skin, showed that maximal tumour to skin ratios were observed at ≤ 24 h with FosPEG 2% and 8%, whilst skin photosensitivity studies showed Foscan® induces more damage compared to the liposomes at drug-light intervals of 96 and 168 h. PDT treatment at 24h post-administration (0.05 mg kg⁻¹) showed higher tumour necrosis using pegylated liposomal formulations in comparison to Foscan®, which is attributed to the higher tumour uptake and blood plasma concentrations. Clinically, this improved selectivity has the potential to reduce not only normal tissue damage, but the drug dose required and cutaneous photosensitivity.
authors: Division of Surgery and Interventional Science, National Medical Laser Centre, University College London, London, UK. m.bovis@ucl.ac.uk
authors: Melissa J
authors: MJ
authors: Bovis
authors: Josephine H
authors: JH
authors: Woodhams
authors: Marilena
authors: M
authors: Loizidou
authors: Dietrich
authors: D
authors: Scheglmann
authors: Stephen G
authors: SG
authors: Bown
authors: Alexander J
authors: AJ
authors: Macrobert
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D005260:Female; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008027:Light; D008081:Liposomes; D008652:Mesoporphyrins / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011092:Polyethylene Glycols; C072269:temoporfin