Original Article Development and optimization of thiolated dendrimer as a viable mucoadhesive excipient for the controlled drug delivery: An acyclovir model formulation Sarath K. Yandrapu, PhD a , Parijat Kanujia, PhD b , Kishore B. Chalasani, PhD c , Lakshminarasu Mangamoori, PhD d , Ramanamurthy V. Kolapalli, PhD a, ⁎ , Abhay Chauhan, PhD e a Andhra University College of Pharmaceutical Sciences, Andhra University, Visakhapatnam, AP, India b Institute of Chemical and Engineering Sciences, Jurong Island Singapore c Merrion Pharmaceuticals, Citywest Business Campus, Dublin 24, Ireland d Institute of Science and Technology, JNTU, Hyderabad, AP, India e School of Pharmacy, Concordia University, Mequon, Wisconsin, USA Received 21 April 2012; accepted 12 October 2012 Abstract In the present study we report the development of novel thiolated dendrimers for mucoadhesive drug delivery. The thiolated dendrimers were synthesized by conjugating PAMAM dendrimer (G3.5)with cysteamine at two different molar ratios, i.e. 1:30 (DCys1) and 1:60 (DCys2). The thiolated dendrimers were further encapsulated with acyclovir (DCys1Ac and DCys2Ac) and the conjugates were characterized for thiol content, drug loading, drug release, and mucoadhesive behavior. The thiolated dendrimer conjugates showed thiol content of 10.56±0.34 and 68.21±1.84 μM/mg of the conjugate for DCys1 and DCys2, respectively. The acyclovir loading was observed to be highest in dendrimer drug conjugate (DAc) compared to other DCys1Ac and DCys2Ac conjugates. The thiolated dendrimers showed sustained release of acyclovir and showed higher mucoadhesion. The in vitro mucoadhesive activity of DCys2Ac was 1.53 and 2.89 fold higher mucoadhesion compared to DCys1Ac and DAc, respectively. These results demonstrated the usefulness of thiolated dendrimers as a mucoadhesive carrier and represent a novel platform for drug delivery. From the Clinical Editor: This study demonstrates the utility of thiolated dendrimers as mucoadhesive carriers as reported in an acyclovir delivery model system. © 2013 Elsevier Inc. All rights reserved. Key words: Muco adhesion; Drug delivery; Dendrimers; Thiol polymers; Acyclovir formulations The concept of mucoadhesion has gained interest in the early 1980s and has become a promising strategy in developing novel delivery systems for enhanced bioavailability. 1 The advantages of mucoadhesive systems include i) enhanced contact time between the dosage form and absorbing membrane vis-a-vis drug bioavailability compared to conventional formulations; ii) mucoadhesive formulations maintain a concentration gradient between the dose to be absorbed and mucus membrane thereby improving the passive diffusion characteristics of poorly permeable drugs 2 ;iii) mucoadhesive polymers such as poly (acrylic acid) derivatives and chitosan showed increased epithelial permeability of many drugs 3,4 ;iv) enhanced per oral protein delivery by minimizing the effect of enzymatic degradation. 5–7 Earlier published literature demonstrated con- siderable promise in the development of mucoadhesive delivery systems for Various applications. 8 However, with conventional polymeric mucoadhesive materials the mucoadhesion is weak due to non-covalent interactions such as electrostatic association, hydrogen bonding, and Van-der Waals forces. In the recent years, efforts are being made to develop new types of mucoadhesive polymers that form a covalent bonding with the mucous membrane. In this regard, various groups 9,10 have carried out extensive investigations on thiol containing polymers (the so called thiomers) as mucoadhesive formulation excipients for various applications. The immobilized thiol groups on the POTENTIAL CLINICAL RELEVANCE Nanomedicine: Nanotechnology, Biology, and Medicine 9 (2013) 514 – 522 nanomedjournal.com ⁎ Corresponding author: A.U. College of Pharmaceutical Sciences, Andhra University, Isakhapatnam, A.P, India 530 003. E-mail address: sarathky@gmail.com (R.V. Kolapalli). 1549-9634/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.nano.2012.10.005 Please cite this article as: Yandrapu SK, et al, Development and optimization of thiolated dendrimer as a viable mucoadhesive excipient for the controlled drug delivery: An acyclovir model formulation. Nanomedicine: NBM 2013;9:514-522, http://dx.doi.org/10.1016/j.nano.2012.10.005