International Journal of Pharmaceutics 441 (2013) 181–191 Contents lists available at SciVerse ScienceDirect International Journal of Pharmaceutics jo ur nal homep a ge: www.elsevier.com/locate/ijpharm Polyox and carrageenan based composite film dressing containing anti-microbial and anti-inflammatory drugs for effective wound healing Joshua S. Boateng ∗,1 , Harshavardhan V. Pawar 1 , John Tetteh Department of Pharmaceutical, Chemical & Environmental Sciences, School of Science, University of Greenwich at Medway, Central Avenue, Chatham Maritime, ME4 4TB, Kent, UK a r t i c l e i n f o Article history: Received 27 October 2012 Received in revised form 28 November 2012 Accepted 29 November 2012 Available online 8 December 2012 Keywords: Antibacterial Film dressing In vitro drug release Mucoadhesion Wound healing Plasticiser a b s t r a c t Polyethylene oxide (Polyox) and carrageenan based solvent cast films have been formulated as dress- ings for drug delivery to wounds. Films plasticised with glycerol were loaded with streptomycin (30%, w/w) and diclofenac (10%, w/w) for enhanced healing effects in chronic wounds. Blank and drug loaded films were characterised by texture analysis (for mechanical and mucoadhesive properties), scanning electron microscopy, differential scanning calorimetry, X-ray diffraction and Fourier transform infrared spectroscopy. In addition, swelling, in vitro drug release and antibacterial studies were conducted to fur- ther characterise the films. Both blank and drug loaded films showed a smooth, homogeneous surface morphology, excellent transparency, high elasticity and acceptable tensile (mechanical) properties. The drug loaded films showed a high capacity to absorb simulated wound fluid and significant mucoadhesion force which is expected to allow effective adherence to and protection of the wound. The films showed controlled release of both streptomycin and diclofenac for 72 h. These drug loaded films produced higher zones of inhibition against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli compared to the individual drugs zones of inhibition. Incorporation of streptomycin can prevent and treat chronic wound infections whereas diclofenac can target the inflammatory phase of wound healing to relieve pain and swelling. © 2012 Elsevier B.V. All rights reserved. 1. Introduction A wound is defined as disruption of normal anatomic struc- ture and function (Boateng et al., 2008) and represents damage of natural defence barriers which encourages invasion by micro- organisms (Kumar and Leaper, 2005). Wound repair normally involves systematic, co-ordinated and balanced activity of inflam- matory, vascular, connective tissue and epithelial cells (Boateng et al., 2008). The existence of a variety of wound types with diverse healing approaches has resulted in the introduction of different types of wound dressings for successful wound healing. Wound infection is one of the most significant factors that delay healing when microorganisms compete with the host immune system and subsequently invade viable tissue. Most wound infections involve aerobes (Escherichia coli, Staphylococcus aureus, and Streptococcus Abbreviations: ATR, attenuated total reflectance; BLK, blank; BSA, bovine serum albumin; CAR, carrageenan CFU-colony forming units; DLF, diclofenac; DL, drug loaded; DSC, differential scanning calorimetry; FTIR, Fourier transform infra red; Fmax, maximum force; GLY, glycerol; POL, polyox; SEM, scanning electron microscopy; STP, streptomycin; SWF, simulated wound fluid; TA, texture analysis; XRD, X-ray diffraction; WOA, work of adhesion; ZOI, zone of inhibition. ∗ Corresponding author. Tel.: +44 0208 331 8980; fax: +44 0208 331 9805. E-mail addresses: J.S.Boateng@gre.ac.uk, joshboat@hotmail.com (J.S. Boateng). 1 Joint First Authors. pyogenes) and anaerobes (Pseudomonas aeruginosa, Bacteroides fragilis, Peptostreptococcus spp., Clostridium spp., Prevotella spp., and Fusobacterium spp.) (Brook and Frazier, 1998; Duerden, 1994). Many published literature references refer to a figure of 10 6 CFU/ml of wound fluid or 10 5 CFU/g of tissue as a criterion for infection (White et al., 2001). Chronic wounds associated with ulcers and diabetes mellitus are susceptible to infection (Bowler et al., 2001) and up to 75% of chronic burn injuries also involve some form of infection (Revathi et al., 1998). Effective management of wound infection necessitates reduced exogenous microbial contamination (bio-burden), debridement of devitalised tissue, use of appropriate dressing and topical and systemic broad-spectrum antimicrobial agents, maximisation of immune resistance and provision of adequate nutrition (Bowler et al., 2001). Antimicrobial agents such as antiseptics have high specificity to treat wound infection and ultimately improve wound healing (Forbes, 1961). However, the emergence of microbial resis- tance has resulted in the need to find alternative treatments for wound infections. In addition, systemic antibiotic treatment can be difficult in certain ulcers such as diabetic ulcers due to the poor blood circulation at the extremities (Bowler et al., 2001). In mod- ern wound care practice, antibiotics such as neomycin, bacitracin, streptomycin (STP), gentamycin and polymixin and/or combina- tions are used to treat chronic wounds (Bowler et al., 2001; Howes, 1947; Pielesz et al., 2011). 0378-5173/$ – see front matter © 2012 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.ijpharm.2012.11.045