Research Article For reprint orders, please contact: reprints@futuremedicine.com Liposome-encapsulated fsh oil protein-tagged gold nanoparticles for intra-articular therapy in osteoarthritis Amrita Sarkar 1,2 , Edmund Carvalho ‡,1,3 , Anisha A D’souza ‡,1 & Rinti Banerjee* ,1 1 Department of Biosciences & Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, 400076, India 2 Department of Pediatrics, Division of Hematology, The Children’s Hospital of Philadelphia, 3615 Civic Center Blvd, Philadelphia, PA 19104, USA 3 Department of Microbiology, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA *Author for correspondence: Tel.: +91 22 2576 7868; Fax: +91 22 2572 3480; rinti@iitb.ac.in ‡ Authors contributed equally Aim: To provide multilayered combination therapies encompassing nanoparticles and organic peptides and to assess their effcacy in the treatment of arthritis. Materials & methods: Fish oil protein (FP) was isolated from fsh oil glands and tagged with spherical gold nanoparticles (GNPs). Tagged GNPs were encapsulated in DPPC liposomes (FP-GNP-DPPC) and characterized. Results & conclusion: FP increased the hydrophilicity of GNP, while encapsulation of FP-GNP within liposomes increased the hydrophobicity. In vitro release studies of FP-GNP-DPPC exhibited sustained release of FP in simulated synovial fuid. FP-GNP- DPPC injected into intra-articular joints of rats displayed anti-osteoarthritic effects in osteoarthritic rat model. This is the frst study to report the anti-osteoarthritic activity of FP and DPPC encapsulated FP-GNP liposomes. First draft submitted: 27 June 2018; Accepted for publication: 10 December 2019; Published online: 22 March 2019 Keywords: apoptosis • collagenase-induced osteoarthritis • DPPC liposome • fsh oil protein • gold nanoparticles • surface-active phospholipid mimetic Management of osteoarthritis (OA) aims at palliative relief by nonsteroidal anti-inflammatory drugs, corticosteroids, disease-modifying anti-rheumatic drugs and analgesics. Rapid clearance and large volume of distribution lead to poor efficacy of orally administered drugs and mandates repeated dosing. This is associated with side effects that include gastric ulcers and bleeding [1,2]. Consequently, COX2 inhibitors have to be accompanied with gastric protective therapies [2]. Additionally, irreversible suppression of immune system is a limitation of drug delivery. To counteract these effects, nutraceutical interventions, including glucosamine natural therapies such as protein extracts [3], homeopathy [4], natural extracts [3,5], collagen hydrolysates, soyabean unsaponifiables and macronutrients, have been the crest of prevention and treatment of OA [5,6,7]. Although drugs attain systemic levels through oral administration, they fail to exhibit specificity to joints, as OA is restricted to articular joints. Targeted delivery of OA drugs to cartilage or synovial capsule are promising interventions in OA. Intra-articular therapy is one of the most effective routes of administration in bone and joint diseases [8,9]. Nanoencapsulated delivery systems, on the other hand, provide the ideal interventions for targeted intra-articular delivery and other disease condition [10], that allow prolonged retention in the joints and promote sustained release of drugs [11,12,13]. The nanometric scale of the particles prevents phagocytic uptake and related cascading inflammation, unlike microparticles [14]. Various nanocarrier systems like liposomes [15,16,17,18], supermagnetic iron oxide nanoparticles [19], polymeric nanoparticles [20], hydrogels [21], have been reported as intra-articular delivery vehicles. Liposomes are popularly explored, since phosphatidylcholine, especially dipalmitoyl phosphatidylcholine (DPPC), a major surface-active phospholipid component of oligolamellar layer coating the articular cartilage, provides lubrication and protection and is a key component of synovial fluid [22,23]. DPPC-based products have already reported extensive benefits for treatment of OA patients [8,24]. DPPC liposomes as nano-carriers impart a dual role of drug delivery as well as for bone joint lubrication [25]. Nanomedicine (Lond.) (Epub ahead of print) ISSN 1743-5889 10.2217/nnm-2018-0221 C  2019 Future Medicine Ltd