Development of a Novel Polymeric Nanocomposite Complex for Drugs with Low Bioavailability
Semi-synthetic biopolymer complex (SSBC) nanoparticles were investigated as a potential oral drug delivery system to enhance the bioavailability of a poorly water-soluble model drug acyclovir (ACV). The SSBCs were prepared from cross-linking of hydroxyl groups on hyaluronic acid (HA) with poly(acrylic acid) (PAA) resulting in ether linkages. Thereafter, conjugation of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) onto HA-PAA was accomplished using a 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS)-promoted coupling reaction. Nanoparticle powders were prepared by spray drying of drug-loaded SSBC emulsions in a laboratory nano spray dryer. The prepared SSBC was characterized by Fourier transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), 1H nuclear magnetic resonance (NMR) imaging, and X-ray diffraction (XRD) spectroscopy. The average particle size was found to be 257.92 nm. An entrapment efficiency of 85% was achieved as ACV has enhanced affinity for the hydrophobic inner core of the complex. It was shown that SSBC improved the solubility of ACV by 30% and the ex vivo permeation by 10% compared to the conventional ACV formulation, consequentially enhancing its bioavailability. Overall, this study resulted in the successful preparation of a hybrid chemically conjugated SSBC which has great potential for enhanced oral absorption of ACV with possible tuneable ACV permeability and solubility, producing an “intelligent” nanoenabled drug delivery system.
KEY WORDSacyclovir nanoenabled drug delivery systems oral bioavailability semi-synthetic biopolymer complex spray drying
The Wits Advanced Drug Delivery Platform Research Unit acknowledges funding from the National Research Foundation of South Africa.
Compliance with Ethical Standards
Ethics approval was obtained from the Animal Ethics Screening Committee of the University of the Witwatersrand for the use of the epithelial tissue.
- 1.Joshi AJ, Patel RP. Role of biodegradable polymer in drug delivery. Int J Curr Pharm Res. 2012;4:74–81.Google Scholar
- 3.van Hest JCM. Biosynthetic-synthetic polymer conjugates. J Macromol Sci C Polym Rev. 2007;47:63–92.Google Scholar
- 8.Nayak S, Marulkar K, Bhaskar V, Chivate A. Preparation and evaluation of hot melt extrudes of acyclovir. WJPPS. 2014;3:1073–83.Google Scholar
- 15.Laurent TC. The chemistry, biology and medical applications of hyaluronan and its derivatives. London: Portland Press; 1998.Google Scholar
- 19.Li F, Bae BC, Na K. Acetylated hyaluronic acid/photosensitizer conjugate for the preparation of nanogels with controllable phototoxicity: synthesis, characterization, autophotoquenching properties, and in vitro phototoxicity against HeLa cells. Bioconjug Chem. 2010;21:1312–20.CrossRefPubMedGoogle Scholar
- 30.Kumar B, Jain SK, Prajapati SK, Mahor A, Kumar A. Development and characterization of transdermal microemulsion gel for an antiviral drug. Int J Pharm Sci Res. 2010;1:57–74.Google Scholar
- 32.Fulda S, Gorman MA, Hori O, Samali A. Cellular stress responses: cell survival and cell death. Int J Cell Biol. 2010;2009:1–23.Google Scholar
- 41.Sankar R, Jain S. Approaches for enhancing the bioavailability of acyclovir: a critical review. Int J Pharm Biosci. 2013;4(4):623–34.Google Scholar