title: Bi-directionally selective bone targeting delivery for anabolic and antiresorptive drugs: a novel combined therapy for osteoporosis?
abstract: Osteoporosis is a progressive systemic skeletal disease, in which the equilibrium of bone resorption and bone formation is disturbed. The drugs for osteoporosis can be divided into two categories according to their predominant effects: antiresorptive drugs and anabolic drugs. Antiresorptive drugs are designed to inhibit bone resorption and anabolic drugs are aiming to stimulate bone formation. On the other hand, most antiresorptive drugs usually decrease anabolic activities and reduce bone formation, while anabolic drugs can unintendedly increase bone resorption. Furthermore, both types of drugs show no preferential distribution in bone and can locate generally in the areas of both bone formation and bone resorption. Consequently, the non-specific interaction of these drugs with non-targeting area and cells can lead to a compromised efficacy. Combined therapies of antiresorptive and anabolic drugs do not necessarily yield superiority when compared to monotherapy. Here, basing on the targeting cells of these two kinds of drugs and the spatial distribution of osteoblasts and osteoclasts, we propose a novel drug delivery system of bi-directionally selective targeting in order to facilitate the efficacy of antiresorptive and anabolic drugs in combined therapy. In the system, an antiresorptive drug will be linked with a peptide of the eight repeating sequences of aspartate--(Asp)8 that can preferentially guide the drugs to bone resorption zone; while an anabolic drug linked with a peptide of six repeats of the sequence aspartate, serine, serine--(Asp-Ser-Ser)6 that can favorably guide the drugs to bone formation zone. The novel delivery system will improve the specific interaction between the drugs and their targeting cells. Furthermore, the system will reduce the non-specific interaction of the anabolic and antiresorptive drugs with their respective non-targeting cells, which will maximally reduce their side-effects. Therefore, we postulate that the new bone targeting drug delivery system will be a blessing for osteoporotic patients.
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China; School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Stomatology, Ningxia Medical University, Yinchuan 750004, China.
authors.forename: Hualin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Dong
authors.affiliation: School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Jin
authors.affiliation: School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Hu
authors.affiliation: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400044, China. Electronic address: kaiyong_cai@cqu.edu.cn.
authors.forename: Kaiyong
authors.initials: K
authors.lastname: Cai
authors.affiliation: School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China. Electronic address: dentistmacn@aliyun.com.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Ma
authors.affiliation: School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou 325027, China; Department of Oral Implantology and Prosthetic Dentistry, Academic Centre for Dentistry Amsterdam (ACTA), Research Institute MOVE, VU University and University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Gang
authors.initials: G
authors.lastname: Wu
mesh_terms: D045930:Anabolic Agents / Q000737:chemistry; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism*; D016503:Drug Delivery Systems; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D045930:Anabolic Agents; D050071:Bone Density Conservation Agents; D001224:Aspartic Acid