2013 http://informahealthcare.com/drt ISSN: 1061-186X (print), 1029-2330 (electronic) J Drug Target, Early Online: 1–10 ! 2013 Informa UK Ltd. DOI: 10.3109/1061186X.2013.771778 ORIGINAL ARTICLE Hyperbranched dendritic nano-carriers for topical delivery of dithranol Udita Agrawal, Neelesh Kumar Mehra, Umesh Gupta, and N. K. Jain Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar, Madhya Pradesh, India Abstract The purpose of the current investigation was to explore the potential of polypropylene imine (PPI) dendrimers to deliver dithranol (DIT) topically and to evaluate its encapsulation, permeation and skin irritation potential. PPI (5.0 generation, 5.0 G) dendrimers and DIT-loaded PPI (DIT–PPI) were prepared and characterized by spectroscopy and transmission electron microscopy. DIT encapsulation, in vitro skin permeation study, skin irritation studies, fluorescent studies and tape stripping studies were performed. Loading of DIT was found to be pH dependent with maximum encapsulation at acidic pH (1.0  0.02, 17.2  0.56 and 57.1  1.32% at 7.4, 5.5 and 1.2 pH, respectively). DIT–PPI showed significantly enhanced permeation rate constant and lesser skin irritation (11.61  1.80 mg/cm 2 /h and 1.0, respect- ively) when compared with the plain DIT solution (2.72  0.31 mg/cm 2 /h and 2.3, respectively). Skin separation studies and confocal laser scanning microscope images showed that the dye- loaded dendrimers exhibits deposition of dye in pilosebaceous compartment. These studies demonstrate that PPI can be exploited to improve the topical bioavailability of the molecules in a controlled pattern. The enhanced accumulation of DIT via dendrimer carrier within the skin might help optimize targeting of this drug to the epidermal and dermal sites, thus creating new opportunities for well-controlled, modern topical application of DIT for the treatment of psoriasis. Keywords Dendrimers, dithranol, psoriasis, topical drug delivery History Received 29 August 2012 Revised 17 January 2013 Accepted 28 January 2013 Published online 17 April 2013 Introduction Psoriasis is accepted as an autoimmune multi-factorial, T-lymphocyte-mediated autoimmune disease of the dermis and epidermis, whose development is exaggerated by physical distress, psychological stress, drug administration, alcohol abuse, smoking and infection, etc [1,2]. Previously, it was considered as a disease of altered keratinocyte proliferation, hyper parakeratosis, epidermal accumulation of polymorpho- nuclear leukocyte (PMN) and dermal inflammation which was based on prominent histological and clinical features, such as epidermal thickening and scaling [3,4]. The auto- immune changes in psoriasis initially involve T-lymphocytes that completely disturb immune regulation of the skin, resulting in secretion of various pro-inflammatory mediators [5,6]. Increase in these mediators stimulates proliferation of atypical keratinocytes and development of inflammatory changes in the skin. Dithranol (DIT) is a highly effective antipsoriatic com- pound having a direct inhibitory effect on keratinocyte proliferation [7–9]. DIT inhibits PMN function [10], modu- lates the arachidonic acid metabolism [11] and is also found to be capable of modulating surface receptors of epidermal cells [12]. As therapeutic interaction of DIT occurs with the electron transport chain on the inner mitochondrial membrane, the target organelle for DIT is mitochondria, which results in the reduction of ATP synthesis. Simultaneously, many enzymes allied with cell proliferation are reportedly inhibited by DIT, viz. G-6-P dehydrogenase, ornithine decarboxylase, lipooxygenase and protein kinase C [8]. However, mode of action of DIT is not completely understood yet. Disadvantages of DIT include instability in the presence of light [13], irritation when applied on the skin and staining of clothes. To overcome staining problem, a preparation has been introduced incorporating anthralin into a vehicle that delivers the drug at the body temperature which would minimize staining of clothes and household items [14]. Moreover, only few percent of DIT is released from a white soft paraffin suspension, which is one of the common formulations used in dermatology, and that most of this fraction persists in the stratum corneum (SC) without reaching deeper epidermal regions [15]. Because of its inconvenience and side effects, newer delivery systems have been investigated to circumvent these problems and to draw maximum benefit of the drug by making it available to the deeper skin layers. Recently, Raza et al. successfully developed and characterized the DIT-loaded nanoemulsomes [7] and microemulsions [16] for topical delivery. The hyperbranched polypropylene imine (PPI) dendrimer generated a great deal of interest in controlled and targeted drug delivery owing to their mono-dispersity, high-density of peripheral functional group, well-defined precise shape and size, surface chemistries, host–guest interaction chemistry, Address for correspondence: Prof. N. K. Jain, Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar, Madhya Pradesh 470003, India. Tel/Fax: +91- 7582264712. E-mail: jnarendr@yahoo.co.in; neelesh81mph@gmail.com Journal of Drug Targeting Downloaded from informahealthcare.com by 117.204.179.8 on 04/17/13 For personal use only.