QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery

Pooja Jain; Mohd Aamir Mirza; Enam Reyaz; Mirza Adil Beg; Angamuthu Selvapandiyan; Nazeer Hasan; Akbar Naqvi; Naseef Punnoth Poonkuzhi; Mohammad Saheer Kuruniyan; Harlokesh Narayan Yadav; Farhan J Ahmad; Zeenat Iqbal

doi:10.1021/acsomega.3c07092

QbD-Assisted Development and Optimization of Doxycycline Hyclate- and Hydroxyapatite-Loaded Nanoparticles for Periodontal Delivery

ACS Omega. 2024 Jan 18;9(4):4455-4465. doi: 10.1021/acsomega.3c07092. eCollection 2024 Jan 30.

Affiliations

¹ Department of Pharmaceutics, School of Pharmaceutical Education and Research, SPER, Jamia Hamdard, New Delhi 110062, India.
² Department of Molecular Medicine, Jamia Hamdard, New Delhi 110062, India.
³ Department of Dentistry, HIMSR, New Delhi 110062, India.
⁴ Department of Pharmaceutics, Moulana College of Pharmacy, Perinthalmanna, Kerala 679321, India.
⁵ Department of Dental Technology, COAMS, King Khalid University. Abha 61421, Saudi Arabia.
⁶ Department of Pharmacology, AIIMS, New Delhi, 110608, India.

Abstract

The current research aims to develop a carrier system for the delivery of a matrix metalloproteinase (MMP) inhibitor along with a bioceramic agent to the periodontal pocket. It is proposed that the present system, if given along with a systemic antibiotic, would be a fruitful approach for periodontitis amelioration. To fulfill the aforementioned objective, a doxycycline hyclate- and hydroxyapatite-adsorbed composite was prepared by a physical adsorption method and successfully loaded inside sodium alginate-chitosan nanoparticles and optimized based on particle size and drug content. Optimized formulation was then subjected to different evaluation parameters like encapsulation efficiency, hydroxyapatite content, ζ potential, surface morphology, in vitro drug release, cell line studies, and stability studies. For the optimized formulation, particle size, polydispersity index (PDI), entrapment efficiency, ζ potential, and drug content were found to be 336.50 nm, 0.23, 41.77%, -13.85 mV, and 14.00%, respectively. The surface morphology of the placebo and adsorbed composite-loaded nanoparticles as observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the spherical shape and rough surface of the particles. In gingival crevicular fluid (GCF) 7.6, a sustained drug release profile was obtained up to 36 h. In vitro % viability studies performed on murine fibroblast cells (NIH3T3) and human periodontal ligament (hPDL) cell lines confirmed the proliferative nature of the formulation. Also, when subjected to stability studies for 4 weeks, particle size, PDI, and drug content did not vary considerably, thereby ensuring the stable nature of nanoparticles. Henceforth, sodium alginate-chitosan nanoparticles appeared to be a good carrier system for doxycycline hyclate and hydroxyapatite for periodontal therapy. If given along with a system antibiotic, the system will serve as a fruitful tool for infection-mediated periodontal regeneration and healing.