pH-Sensitive nanocarrier assisted delivery of adenosine to treat osteoporotic bone loss

Newman, Hunter; Hoque, Jiaul; Shih, Yu‐Ru V.; Marushack, Gabrielle; Ko, Unghyun; Gonzales, Gavin; Varghese, Shyni

doi:10.1039/d2bm00843b

Cited by 7 publications

(5 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Methylprednisolone release from the BPL molecules into PBS as a function of time was evaluated over a period of 14 days. 45 The release profile was steady and sustained. After 1 day, ~9.3% of the methylprednisolone was released in PBS, and this value was increased to ~14.3% by day 3, and by 14 days, 32.4% of the drug was released from the BPL molecules (Figure 7c ).…”

Section: Resultsmentioning

confidence: 94%

“…The successful conjugation of the methylprednisolone to the BPL molecules was validated with NMR and the methylprednisolone incorporation to the G2HP BPL molecules was calculated to be ~17% of the total mass (Figures S22–S25). Methylprednisolone release from the BPL molecules into PBS as a function of time was evaluated over a period of 14 days 45 . The release profile was steady and sustained.…”

Section: Resultsmentioning

confidence: 99%

“…Methylprednisolone release from the BPL molecules into PBS as a function of time was evaluated over a period of 14 days. 45 The release profile was steady and sustained.…”

Section: G2hp Bpl Molecules As Nanocarriers For Methylprednisolonementioning

confidence: 94%

“…The release kinetics of 6‐alpha‐methylprednisolone from the BPL molecules was carried out in PBS as a function of time over 14 days. 45 The G2HP BPL molecules conjugated with the drug were dissolved in PBS at a concentration of 10 mg/ml. The solutions (10 mg/ml) were loaded into dialysis bags (MWCO = 2 kDa; Cat.…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Branched poly‐l‐lysine for cartilage penetrating carriers

Gonzales,

Hoque,

Gilpin

et al. 2023

Bioengineering & Transla Med

Self Cite

View full text Add to dashboard Cite

Joint diseases, such as osteoarthritis, often require delivery of drugs to chondrocytes residing within the cartilage. However, intra‐articular delivery of drugs to cartilage remains a challenge due to their rapid clearance within the joint. This problem is further exacerbated by the dense and negatively charged cartilage extracellular matrix (ECM). Cationic nanocarriers that form reversible electrostatic interactions with the anionic ECM can be an effective approach to overcome the electrostatic barrier presented by cartilage tissue. For an effective therapeutic outcome, the nanocarriers need to penetrate, accumulate, and be retained within the cartilage tissue. Nanocarriers that adhere quickly to cartilage tissue after intra‐articular administration, transport through cartilage, and remain within its full thickness are crucial to the therapeutic outcome. To this end, we used ring‐opening polymerization to synthesize branched poly(l‐lysine) (BPL) cationic nanocarriers with varying numbers of poly(lysine) branches, surface charge, and functional groups, while maintaining similar hydrodynamic diameters. Our results show that the multivalent BPL molecules, including those that are highly branched (i.e., generation two), can readily adhere and transport through the full thickness of cartilage, healthy and degenerated, with prolonged intra‐cartilage retention. Intra‐articular injection of the BPL molecules in mouse knee joint explants and rat knee joints showed their localization and retention. In summary, this study describes an approach to design nanocarriers with varying charge and abundant functional groups while maintaining similar hydrodynamic diameters to aid the delivery of macromolecules to negatively charged tissues.

show abstract

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

“…Methylprednisolone release from the BPL molecules into PBS as a function of time was evaluated over a period of 14 days. 45 The release profile was steady and sustained.…”

Section: G2hp Bpl Molecules As Nanocarriers For Methylprednisolonementioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Branched poly‐l‐lysine for cartilage penetrating carriers

Gonzales,

Hoque,

Gilpin

et al. 2023

Bioengineering & Transla Med

Self Cite

View full text Add to dashboard Cite

show abstract

“…This ketal acts as the pH‐responsive element in the biomaterial system. [ 138 ] This pH‐responsive, adenosine‐doped system demonstrates the capability to release adenosine in a sustained manner within the acidic OC microenvironment, thereby reducing bone loss associated with osteoporosis induced by ovariectomy in mice.…”

Section: Construction and Application Of Biomaterials In Oc Modulationmentioning

confidence: 99%

Bioactives and Biomaterial Construction for Modulating Osteoclast Activities

He,

Jiang,

Dong

2023

Adv Healthcare Materials

View full text Add to dashboard Cite

Bone tissue constitutes 15–20% of human body weight and plays a crucial role in supporting the body, coordinating movement, regulating mineral homeostasis, and hematopoiesis. The maintenance of bone homeostasis relies on a delicate balance between osteoblasts and osteoclasts. Osteoclasts, as the exclusive “bone resorbers” in the human skeletal system, are of paramount significance yet often receive inadequate attention. When osteoclast activity becomes excessive, it frequently leads to various bone metabolic disorders, subsequently resulting in secondary bone injuries, such as fractures. This not only reduces life quality of patients, but also imposes a significant economic burden on society. In response to the pressing need for biomaterials in the treatment of osteoclast dysregulation, there is a surge of research and investigations aimed at osteoclast regulation. Promising progress is achieved in this domain. This review seeks to provide a comprehensive understanding of how to modulate osteoclast activities. It summarizes bioactive substances that influence osteoclasts and elucidates strategies for constructing related biomaterial systems. It offers practical insights and ideas for the development and application of biomaterials and tissue engineering, with the hope of guiding the clinical treatment of osteoclast‐related bone diseases using biomaterials in the future.

show abstract