Journal of Colloid and Interface Science 258 (2003) 415–423 www.elsevier.com/locate/jcis Cross-linked polyvinylpyrrolidone nanoparticles: a potential carrier for hydrophilic drugs Dhruba Jyoti Bharali, Sanjeeb Kumar Sahoo, 1 Subho Mozumdar, and Amarnath Maitra ∗ Department of Chemistry, University of Delhi, Delhi 110007, India Received 14 December 2001; accepted 28 October 2002 Abstract Injectable hydrogel polymeric nanoparticles of polyvinylpyrrolidone cross-linked with N,N ′ -methylene bis-acrylamide and encapsulating water-soluble macromolecules such as FITC–dextran (FITC–Dx) have been prepared in the aqueous cores of reverse micellar droplets. These particles are 100 nm and below in diameter with a narrow size distribution. When dispersed in aqueous buffer these particles appear to be transparent and give an optically clear solution. Lyophilized powder of these nanoparticles is redispersable in aqueous buffer without any change in the size and morphology of the particles. The efficiency of FITC–Dx entrapment by these nanoparticles is high (> 70%) and de- pends on the amount of cross-linking agent present in the polymeric material. The release of the entrapped molecules from these nanoparticles depends on the degree of cross-linking of the polymer, particle size, pH of the medium, and extent of loading, as well as temperature.  2003 Elsevier Science (USA). All rights reserved. Keywords: Hydrophilic nanoparticles; PVP; FITC–dextran; AOT; Reverse micelles; Drug encapsulation 1. Introduction During the past two decades there has been a growing interest in the use of hydrogel polymers as carriers for tar- geting drugs at specific sites in the body [1–5]. These poly- meric materials are usually biocompatible, biodegradable, and nonantigenic compounds and are easily dispersible in water. Water-soluble drugs can be incorporated into these hydrogels. The use of hydrophilic polymeric nanoparticles as drug carriers for the purpose of drug targeting is a chal- lenging area of research, as water-soluble drugs, including proteins and nucleic acids in the naked forms or in the forms of prodrugs, are sometimes degradable in the body system and therefore need complete protection from hostile enzymes until they can reach the targeted tissues. A consid- erable amount of effort has been devoted to the creation of nanoparticles for drug delivery systems acceptable for gen- eral systemic use and capable of carrying a drug to its tar- get at the cellular or tissue level. With the advent of re- combinant DNA technology, various types of proteins and * Corresponding author. E-mail address: maitra@giasdl01.vsnl.net.in (A. Maitra). 1 Present address: Department of Pharmaceutical Science, University of Nebraska Medical Center, Omaha, NE 68198-6025, USA. polypeptides are being used as drugs as well as vaccines. Encapsulation of these drugs into liposomes is not very ef- fective, as the loading efficiency into liposomes is very low. Hydrophobic nanoparticles cannot be used for encapsulation of these hydrophilic drugs. Most of the preparative meth- ods being followed up till now have been emulsion-mediated processes, which produce nanoparticles of diameter larger than 100 nm with broad polydispersity [4,10–12]. This size is quite large compared to the histology of the endothelial barrier, whose fenestration is around 50–60 nm in diame- ter or in the case of vasculature in solid tumor sinusoids which are less than 100 nm in diameter [13]. Nanoparti- cles made of polymeric micelles are better targetable ma- terials, particularly for solid tumors, because (i) these parti- cles have a hydrophilic surface and (ii) their sizes are much less than diameter 100 nm [14,15]. However, the bulk cores of these particles are hydrophobic and can dissolve only hy- drophobic drugs. Therefore they are not suitable for encap- sulating hydrophilic water-soluble compounds. The body’s RES, mainly the Kupffer cells in the liver, usually takes up polymeric nanoparticles with hydrophobic surface and, therefore, the residence time of these particles in the blood is small. Surface coverage by amphiphilic polymeric surfac- tants such as poloxamers and poloxamines over the nanopar- ticles significantly increases the blood circulation time but 0021-9797/03/$ – see front matter  2003 Elsevier Science (USA). All rights reserved. doi:10.1016/S0021-9797(02)00099-1