TY - JOUR
T1 - Combination of hyaluronic acid and PLGA particles as hybrid systems for viscosupplementation in osteoarthritis
AU - Mota, Ana Henriques
AU - Direito, Rosa
AU - Carrasco, Marta P.
AU - Rijo, Patricia
AU - Ascensao, Lia
AU - Viana, Ana Silveira
AU - Rocha, Joao
AU - Eduardo-Figueira, Maria
AU - Rodrigues, Maria Joao
AU - Custodio, Luisa
AU - Kuplennik, Nataliya
AU - Sosnik, Alejandro
AU - Almeida, Antonio Jose
AU - Gaspar, Maria Manuela
AU - Reis, Catarina Pinto
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/3/25
Y1 - 2019/3/25
N2 - Hyaluronic acid (HA) is commonly used through intra-articular administration for viscosupplementation in osteoarthritis and other disorders. HA is generally supplied as an injection commonly reported as painful, with strong limitations after treatment. In this study, an alternative delivery system was constructed based on HA hydrogel and poly(lactic-co-glycolic acid) (PLGA) particles with oleic acid. Development studies included the determination of particle toxicity, hemolytic activity, in vitro and in vivo anti-inflammatory activity using macrophages and a murine model, respectively. This study showed that empty PLGA particles presented a mean size of 373 nm, while particles containing HA and oleic acid showed a marked particle size increase. The HA association efficiency was of 73.6% and 86.2% for PLGA particles without and with oleic acid, respectively. The in vitro HA release from PLGA particles revealed a sustained profile. Particles showed a good in vitro cell compatibility and the risk of hemolysis was less <1%, ensuring their safety. The in vivo anti-inflammatory study showed a higher inhibition for HA-loaded PLGA particles when compared to HA solution (78% versus 60%) and they were not different from the positive control, clearly suggesting that this formulation may be a promising alternative to the current HA commercial dosage form.
AB - Hyaluronic acid (HA) is commonly used through intra-articular administration for viscosupplementation in osteoarthritis and other disorders. HA is generally supplied as an injection commonly reported as painful, with strong limitations after treatment. In this study, an alternative delivery system was constructed based on HA hydrogel and poly(lactic-co-glycolic acid) (PLGA) particles with oleic acid. Development studies included the determination of particle toxicity, hemolytic activity, in vitro and in vivo anti-inflammatory activity using macrophages and a murine model, respectively. This study showed that empty PLGA particles presented a mean size of 373 nm, while particles containing HA and oleic acid showed a marked particle size increase. The HA association efficiency was of 73.6% and 86.2% for PLGA particles without and with oleic acid, respectively. The in vitro HA release from PLGA particles revealed a sustained profile. Particles showed a good in vitro cell compatibility and the risk of hemolysis was less <1%, ensuring their safety. The in vivo anti-inflammatory study showed a higher inhibition for HA-loaded PLGA particles when compared to HA solution (78% versus 60%) and they were not different from the positive control, clearly suggesting that this formulation may be a promising alternative to the current HA commercial dosage form.
KW - Osteoarthritis
KW - Hyaluronic acid
KW - PLGA particles
KW - In vitro release
KW - In vivo anti-inflammatory activity
UR - http://www.scopus.com/inward/record.url?scp=85060554783&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2019.01.017
DO - 10.1016/j.ijpharm.2019.01.017
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SN - 0378-5173
VL - 559
SP - 13
EP - 22
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
ER -