title: Development and Evaluation of a Topical Anti-Inflammatory Preparation Containing Dodonaea polyandra Extract.
abstract: OBJECTIVE
  We have previously reported that the Australian Northern Kaanju (Kuuku I'yu) medicinal plant Dodonaea polyandra has anti-inflammatory activity. This is attributed largely to the presence of clerodane diterpenoids contained within the leaf resin. We envisaged developing a topical preparation to treat indications relating to skin inflammation. However, it was unknown whether the resin could be incorporated into a suitable dosage form while retaining the therapeutic value demonstrated in previous work. Therefore, the following study was undertaken to assess parameters of safety and efficacy for a prototype formulation containing the leaf resin extracted from D. polyandra.
  
  
  METHODS
  Using the assessment criteria of optimum appearance, tactile feeling, spreadability and odour, 78 different formulations were developed. Formulation stability was assessed using a centrifugal test with preparations displaying phase separation further modified or re-formulated. A prototype formulation containing 5% w/w plant resin was selected and subjected to in vitro release studies. This was quantified through HPLC analysis using two major bioactive diterpenoids as reference. The prototype formulation was tested for efficacy in a TPA-induced acute murine skin inflammation model as well as a 3D human skin model for irritancy/toxicity (Epiderm™).
  
  
  RESULTS
  The prototype resin cream was a chartreuse-coloured homogenous semisolid preparation that was readily spreadable upon contact with skin with no sensation of tackiness, residual greasiness, or irritation. The optimized cream showed no phase separation after 30 min centrifugation at 825 g. In the TPA-induced inflammation model, the resin formulation significantly reduced ear thickness and interleukin-1 beta levels in mouse ear tissue. The 5% w/w resin cream formulation showed no irritancy in a 3D human skin model.
  
  
  CONCLUSIONS
  Our results demonstrate that bioactive resin from D. polyandra can be formulated into a stable and non-irritant semi-solid dosage form and reduce parameters of acute skin inflammation in vivo. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.
authors.affiliation: Sansom Institute for Health Research, University of South Australia, GPO, Adelaide, South Australia; Flinders Centre for Innovation in Cancer, Flinders University, GPO Box 2100, Adelaide, South Australia.
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Simpson
authors.forename: Xianling
authors.initials: X
authors.lastname: Luo
authors.forename: Jiping
authors.initials: J
authors.lastname: Wang
authors.forename: Yunmei
authors.initials: Y
authors.lastname: Song
authors.forename: David
authors.initials: D
authors.lastname: Claudie
authors.forename: Sanjay
authors.initials: S
authors.lastname: Garg
authors.forename: Nicholas
authors.initials: N
authors.lastname: Smith
authors.forename: Ross
authors.initials: R
authors.lastname: McKinnon
authors.forename: Susan
authors.initials: S
authors.lastname: Semple
mesh_terms: D000208:Acute Disease; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D001315:Australia; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D004195:Disease Models, Animal; D045785:Diterpenes, Clerodane / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology; D004355:Drug Stability; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018515:Plant Leaves; D029631:Sapindaceae / Q000737:chemistry*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D023422:Skin Irritancy Tests
chemical_list: D000893:Anti-Inflammatory Agents; D003879:Dermatologic Agents; D045785:Diterpenes, Clerodane