Strategies and Drug Delivery Systems Used in Bone Targeting: An Overview

The bone, a living tissue in vertebrates, is composed of 60% inorganic minerals such as hydroxyapatite Ca10(PO4)6(OH)2, 30% organic matrix including collagens, proteoglycans and lipids, and 10% of cells and blood vessels (1,2). It provides a rigid framework known as the skeleton. Based on the proportion of the above constituents it is thus classified into two types; cortical is a compact and dense outer layer, while the spongy, honeycomb structured inner layer is known as trabecullar or cancellous. Although bone mainly functions to protect the vital organs and support movements, it also acts as a storage of minerals and a major site of erythropoiesis (3). The highly specified tissue is constantly being metabolized and remodelled throughout life to maintain a healthy skeletal structure to execute these functions. Bone metabolism involves multiple bone cells as key regulators, including osteocytes, osteoblasts, and osteoclasts, which either on their own or in interaction keep the balance between bone catabolism and anabolism (4,5).The process initiates with the stimulation of osteocytes via a mechanosensory stimulation to elicit bone remodelling, recruiting osteoclasts to the old or damaged bone surface, thereby promoting bone resorption (the dominant event in the second phase). The mesenchymal stem cells and bone progenitor cells are recruited to the site at the same time, followed by MSCs differentiating into osteoblasts in the third phase to mediate the bone formation for a sustained time, and finally end with the mineralization of the organic matrix called osteoid to form new bones (6). The schematic representation of the bone remodelling cycle is given in Figure 1. However, when cells or cytokines in any of these four phases are altered, it may result in abnormalities in the bone structures, resulting in alteration of its flexibility and strength, finally culminating into bone metabolic diseases (7, 8, 9). A clinical survey in the year 2020 revealed that approximately 1.5 million Americans suffer from Osteoporosis mediated fragile fractures. Statistics of the cross-sectional studies conducted in the year 2022 amongst postmenopausal women in the state of Punjab itself, revealed the prevalence of approximately 30% osteoporosis and 44% osteopenia respectively (10). Thus, these observations have flagged an alarming signal in the entire country.