Investigation of the treatment potential of Raloxifene-loaded polymeric nanoparticles in osteoporosis: In-vitro and in-vivo analyses

Zhonghua Guo; Rabia Afza; Muhammad Moneeb Khan; Saif Ullah Khan; Muhammad Waseem Khan; Zakir Ali; Sibgha Batool; Fakhar Ud Din

doi:10.1016/j.heliyon.2023.e20107

Investigation of the treatment potential of Raloxifene-loaded polymeric nanoparticles in osteoporosis: In-vitro and in-vivo analyses

Heliyon. 2023 Sep 13;9(9):e20107. doi: 10.1016/j.heliyon.2023.e20107. eCollection 2023 Sep.

Authors

Zhonghua Guo¹, Rabia Afza², Muhammad Moneeb Khan^{3

4}, Saif Ullah Khan⁵, Muhammad Waseem Khan⁶, Zakir Ali^{3

4}, Sibgha Batool^{3

4}, Fakhar Ud Din^{3

4}

Affiliations

¹ Department of Orthopaedics, Henan Province Hospital of TCM, Zhengzhou City, Henan Province, 450002, China.
² Department of Botany, Hazara University Mansehra KP, Pakistan.
³ Department of Pharmacy Quaid-i-Azam University, 45320, Islamabad, Pakistan.
⁴ Nanomedicine Research Group, Department of Pharmacy Quaid-i-Azam University, 45320, Islamabad, Pakistan.
⁵ Institute of Biotechnology and Microbiology, Bacha Khan University, Charsada, KPK, Pakistan.
⁶ Institute of Pharmaceutical Sciences Khyber Medical University, Peshawar, Pakistan.

Abstract

Osteoporosis (OP), is a systemic bone disorder associated with low bone mass and bone tissue corrosion. Worsening of the disease condition leads to bone delicacy and fracture. Various drugs are available for the treatment of OP, however they have limitations including poor solubility, bioavailability and toxicity. Herein, Raloxifene-loaded polymeric nanoparticles (RLX-PNPs) were developed and investigated for the treatment of OP with possible solutions to the above mentioned problems. RLX-PNPs were prepared by modified ionic gelation method followed by determining their particle properties. FTIR, DSC and PXRD analysis of the RLX-PNPs were performed to check chemical interaction, thermal behavior and crystallinity, respectively. In-vitro release profile of RLX-PNPs was checked in lab setting, whereas its pharmacokinetics was investigated in Sprague-Dawley rats, in-vivo. Finally, the treatment potential of RLX-PNPs was analyzed in OP induced animal model. The optimized PNPs formulation indicated 134.5 nm particle size, +24.4 mV charge and 91.73% % EE. TEM analysis showed spherical and uniform sized particles with no interactions observed in FTIR analysis. In-vitro release of RLX from RLX-PNPs showed more sustained release behavior as compared to RLX-suspension. Moreover, pharmacokinetic investigations showed a significantly enhanced bioavailability of the RLX-PNPs as well as reduced serum levels of alkaline phosphatase and calcium in OP induced rats when compared with RLX-Suspension after oral administration. Findings of this study suggested that the developed RLX-PNPs have the potential to treat OP due to sustained release and improved bioavailability of the incorporated drug.

Keywords: Bioavailability; Oral administration; Osteoporosis; Raloxifene, polymeric nanoparticles.