Transdermal delivery of bisphosphonates using dissolving and hydrogel-forming microarray patches: Potential for enhanced treatment of osteoporosis

Int J Pharm. 2024 Nov 15:665:124642. doi: 10.1016/j.ijpharm.2024.124642. Epub 2024 Aug 28.

Abstract

As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs) are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery of BPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolving and hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawley rats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkaline phosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls. Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVX controls and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. In the distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21 % in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. This proof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternative for weekly osteoporosis management.

Keywords: Alendronic acid; Dissolving microarray patches; Hydrogel-forming microarray patches; Osteoporosis; Risedronate sodium; Transdermal.

MeSH terms

  • Administration, Cutaneous*
  • Alendronate / administration & dosage
  • Alendronate / pharmacokinetics
  • Alkaline Phosphatase / blood
  • Animals
  • Bone Density Conservation Agents* / administration & dosage
  • Diphosphonates / administration & dosage
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacokinetics
  • Female
  • Hydrogels* / administration & dosage
  • Osteoporosis* / drug therapy
  • Ovariectomy
  • Porosity
  • Rats
  • Rats, Sprague-Dawley*
  • Risedronic Acid / administration & dosage
  • Solubility
  • Transdermal Patch

Substances

  • Hydrogels
  • Bone Density Conservation Agents
  • Alendronate
  • Risedronic Acid
  • Diphosphonates
  • Alkaline Phosphatase