QbD‐Based Fabrication of Biomimetic Hydroxyapatite Embedded Gelatin Nanoparticles for Localized Drug Delivery against Deteriorated Arthritic Joint Architecture

Author:

Ain Qurat Ul1,Zeeshan Mahira12,Mazhar Danish1,Zeb Ahmed1,Afzal Iqra1,Ullah Hameed3,Ali Hussain1,Rahdar Abbas4,Díez‐Pascual Ana M.5ORCID

Affiliation:

1. Department of Pharmacy Faculty of Biological Sciences Quaid‐i‐Azam University Islamabad 45320 Pakistan

2. Faculty of Pharmacy Capital University of Science and Technology Islamabad 44000 Pakistan

3. Department of Chemistry Islamia College University Peshawar 25120 Pakistan

4. Department of Physics Faculty of Sciences University of Zabol Zabol 538–98615 Iran

5. Universidad de Alcalá, Facultad de Ciencias Departamento de Química Analítica Química Física e Ingeniería Química Ctra. Madrid‐Barcelona, Km. 33.6 Alcalá de Henares Madrid 28805 Spain

Abstract

AbstractBiomaterials such as nanohydroxyapatite and gelatin are widely explored to improve damaged joint architecture associated with rheumatoid arthritis (RA). Besides joint damage, RA is associated with inflammation of joints and cartilage, which potentiates the need for both bone nucleation and therapeutic intervention. For such purpose, a modified nanoprecipitation method is used herein to fabricate tofacitinib (Tofa)‐loaded nanohydroxyapatite (nHA) embedded gelatin (GLT) nanoparticles (NPs) (Tofa‐nHA‐GLT NPs). The quality by design (QbD) approach is chosen to assess the key parameters that determine the efficiency of the NPs, and are further optimized via Box–Behnken design of experiment. The particle size, polydispersity, zeta potential, and encapsulation efficiency (EE) of the prepared NPs are found to be 269 nm, 0.18, −20.5 mV, and 90.7%, respectively. Furthermore, the NPs have improved stability, skin permeability, and a sustained drug release pattern at pH 6.5 (arthritic joint pH). Moreover, rhodamine‐B loaded nHA‐GLT NPs demonstrates considerably higher cellular uptake by the murine‐derived macrophages than free rhodamine‐B solution. In vitro, cell‐based experiments confirm the good cell biocompatibility with insignificant toxicity. Thus, QbD‐based approach has successfully led to the development of Tofa‐nHA‐GLT NPs with the potential to target inflamed arthritic joint.

Funder

Higher Education Commision, Pakistan

Comunidad de Madrid

Publisher

Wiley

Subject

Materials Chemistry,Polymers and Plastics,Biomaterials,Bioengineering,Biotechnology

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