Nano-Based Biomaterials as Drug Delivery Systems Against Osteoporosis: A Systematic Review of Preclinical and Clinical Evidence

Abstract

Osteoporosis (OP) is one of the most significant causes of morbidity, particularly in post-menopausal women and older men. Despite its remarkable occurrence, the search for an effective treatment is still an open challenge. Here, we systematically reviewed the preclinical and clinical progress in the development of nano-based materials as drug delivery systems against OP, considering the effects on bone healing and regeneration, the more promising composition and manufacturing methods, and the more hopeful drugs and delivery methods. The results showed that almost all the innovative nano-based delivery systems developed in the last ten years have been assessed by preclinical investigations and are still in the preliminary/early research stages. Our search strategy retrieved only one non-randomized controlled trial (RCT) on oligosaccharide nanomedicine of alginate sodium used for degenerative lumbar diseases in OP patients. Further investigations are mandatory for assessing the clinical translation and commercial purposes of these materials. To date, the main limits for the clinical translation of nano-based materials as drug delivery systems against OP are probably due to the low reproducibility of the manufacturing processes, whose specificity and complexity relies on an adequate chemical, structural, and biomechanical characterization, as the necessary prerequisite before assessing the efficacy of a given treatment or process. Finally, an unsatisfactory drug-loading capacity, an uncontrollable release kinetic, and a low delivery efficiency also limit the clinical application.

Novel Nanohydroxyapatite (nHAp)-Based Scaffold Doped with Iron Oxide Nanoparticles (IO), Functionalized with Small Non-Coding RNA (miR-21/124) Modulates Expression of Runt-Related Transcriptional Factor 2 and Osteopontin, Promoting Regeneration of Osteoporotic Bone in Bilateral Cranial Defects in a Senescence-Accelerated Mouse Model (SAM/P6). PART 2

“…12 One of the approaches to enhance healing of OP fractions is the fabrication of novel, personalised biomaterials, and thus far, various scaffolds and drug delivery systems have been developed, yet most of them lack the bioactivity and pleotropic effects to inhibit disease progression at the cellular level. [13][14][15] For this reason, the major goal of the presented study was to fabricate a novel scaffold that not only mechanically supports bone regeneration but also restores the physiological balance between osteoblasts and osteoclasts via targeted and controlled delivery of bioactive molecules into recipient cells. Due to its unique characteristics, including bioactivity, biocompatibility, stability, nontoxic properties, and the presence of -OH groups, which can be employed to conjugate drugs or other chemicals, nanohydroxyapatite (nHAp) has been frequently applied in the fabrication of synthetic bone grafts and bone cements.…”

Targeting Drug Delivery in the Elderly: Are Nanoparticles an Option for Treating Osteoporosis?

“…Naturally evolved targeted nanoparticles, such as viruses, are of breathtaking complexity and show that the packaging/targeting principle is capable of great sophistication [2] and delivers active agents efficiently. At present, however, artificially prepared nanoparticles lack intrabatch homogeneity in size, interbatch reproducibility, in vivo stability, long-term storage stability and upscalability to kilogram amounts, preventing their clinical translation and industrial production [3][4][5][6][7]. This challenge of developing medically safe and effective nanoparticles is reflected in the rather low number of nanoparticles that have already entered clinical use.…”

Multifunctional Tannic Acid-Alendronate Nanocomplexes with Antioxidant, Anti-Inflammatory, and Osteogenic Potency

“…Bone diseases result from a variety of skeletal-related disorders including trauma, osteomyelitis, osteosarcoma, and bone infections, which cause major mobility impediments and mortality to human beings [ 2 , 3 , 4 ]. As previously reviewed, to safely and efficiently treat bone diseases, nano-based materials have been used as drug delivery systems including hydroxyapatite nanoparticles, nano-gel, polysaccharide-based nanoparticles, mesoporous silica nanoparticles, titanium nanotubes, calcium nanoparticles, polyurethane nano-micelles, and biodegradable polymeric nanoparticles [ 5 ]. These systems have great advantages in terms of prolong drug half-lives, targeting drug delivery, improving the stability and efficiency of drugs, stabilizing bioactive agents by encapsulation or surface anchorage, and controlling drug or biological components release at target sites [ 6 , 7 ].…”