Pharmaceutical Research

, Volume 32, Issue 9, pp 2901–2911 | Cite as

Novel Self-assembled, Gel-core Hyaluosomes for Non-invasive Management of Osteoarthritis: In-vitro Optimization, Ex-vivo and In-vivo Permeation

  • Wessam M. El-Refaie
  • Yosra S. R. Elnaggar
  • Magda A. El-Massik
  • Ossama Y. Abdallah
Research Paper



Hyaluronic acid (HA) is an imperative biomaterial with desirable rheological properties to alleviate symptoms of osteoarthritis. Nevertheless, scantly percutaeous permeation of this macromolecule handicaps its effective use for orthopedics and triggers intra-articular injection as the only surrogate. This study presents novel self-assembeld HA-based gel core elastic nanovesicles, (hyaluosomes; GC-HS), for non-invasive transdermal delivery of HA.


GC-HS were prepared with 1% HA using simple film hydration technique. Their size, zeta potential, percentage entrapment efficiency (% EE), elasticity, and ex-vivo transdermal permeation were evaluated compared to conventional liposomes CL. Structure elucidation of the formed novel system was performed using light, polarizing and transmission electron microscopy. In-vivo permeation of GC-HS through knee joints of female Sprague Dawley rats was compared to CL and HA alone.


GC-HS showed nanosize (232.8 ± 7.2), high negative zeta potential (−45.1 ± 8.3) and higher elasticity (size alteration 5.43%) compared to CL. This novel system has self-penetration enhancing properties compared to CL and plain gel. GC-HS showed self-assembled properties and high physically stable for at least 6 months at 4°C. Ex-vivo permeation of HS was significantly higher than CL and plain HA gel alone. In-vivo study exhibited significant six folds increase in transdermal permeation of HA to knee joints from GC-HS compared to plain HA gel.


Novel GC-HS are promising nanogels for topical management of osteoarthritis surrogating the need for intra-articular injection.


elastic nanovesicles gel-core hyaluronic acid osteoarthritis transdermal 



Conventional liposomes


Conventional liposomal gel


Gel core hyaluosomes


Hyaluronic acid




Stratum corneum


Conflict of interest

The authors report no financial or personal conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Wessam M. El-Refaie
    • 1
  • Yosra S. R. Elnaggar
    • 2
  • Magda A. El-Massik
    • 1
  • Ossama Y. Abdallah
    • 2
  1. 1.Department of Pharmaceutics, Faculty of Pharmacy and Drug ManufacturingPharos University in AlexandriaAlexandriaEgypt
  2. 2.Department of Pharmaceutics, Faculty of PharmacyAlexandria UniversityAlexandriaEgypt

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