Leveraging Electrostatic Interactions for Drug Delivery to the Joint

Kumar, S. Bala; Bk, Sharma

doi:10.1089/bioe.2020.0014

Cited by 15 publications

(10 citation statements)

References 138 publications

(177 reference statements)

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“…Interestingly, PEGylation of G1 and G2 BPL molecules did not significantly affect their uptake by cartilage (Figure 2b,d,e), which suggests that the PEGylated BPL molecules possess the optimal surface charge required for cartilage adhesion and penetration. These observations are consistent with previous studies which suggested that the transport of cationic nanocarriers across the cartilage tissue is associated with an optimal surface net charge 11,15,20,24,33 …”

Section: Resultssupporting

confidence: 93%

Branched poly‐l‐lysine for cartilage penetrating carriers

Gonzales,

Hoque,

Gilpin

et al. 2023

Bioengineering & Transla Med

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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.

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Section: Resultssupporting

confidence: 93%

Branched poly‐l‐lysine for cartilage penetrating carriers

Gonzales,

Hoque,

Gilpin

et al. 2023

Bioengineering & Transla Med

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“…In addition, the constituent monomers of Aggrecan contain a large number of negatively charged carboxyl residues and sulfate residues, allowing cationic biomaterials to be attracted to the joints by electrostatic forces 162 . Utilizing this unique property, nanoparticles with a positive charge tend to target the ECM and increase the uptake of chondrocytes through electrostatic attraction 162 . A well-designed green fluorescent protein (GFP) was used to probe the optimal range of positive charge 163 .…”

Section: Targeted Biomaterials In Osteoarthritismentioning

confidence: 99%

Targeted and responsive biomaterials in osteoarthritis

Li¹,

Zhang²,

Han³

et al. 2023

Theranostics

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Osteoarthritis (OA) is a degenerative disease characterized by loss of articular cartilage and chronic inflammation, involving multiple cellular dysfunctions and tissue lesions. The non-vascular environment and dense cartilage matrix in the joints tend to block drug penetration, resulting in low drug bioavailability. There is a desire to develop safer and more effective OA therapies to meet the challenges of an aging world population in the future. Biomaterials have achieved satisfactory results in improving drug targeting, prolonging the duration of action, and achieving precision therapy. This article reviews the current basic understanding of the pathological mechanisms and clinical treatment dilemmas of OA, summarizes and discusses the advances for different kinds of targeted and responsive biomaterials in OA, seeking to provide new perspectives for the treatment of OA. Subsequently, limitations and challenges in clinical translation and biosafety are analyzed to guide the development of future therapeutic strategies for OA. As the need for precision medicine rises over time, emerging multifunctional biomaterials based on tissue targeting and controlled release will become an irreplaceable part of OA management.

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“…Electrostatic interaction causes charged molecules to be adsorbed physically on oppositely charged carriers (Abraham et al, 2020;Kaasalainen et al, 2015;Kumar and Sharma, 2020;Liu et al, 2018;Mauri et al, 2017;Sims et al, 2020;Xiao et al, 2013;Zhao et al, 2012). This strategy has been widely used for gene delivery, where DNA and RNA are negatively charged and carriers positively charged (Nayerossadat et al, 2012;Sung and Kim, 2019;Zhang et al, 2016).…”

Section: Non-covalent Interactionsmentioning

confidence: 99%

Applications of capillary action in drug delivery

Zhao

2021

iScience

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Contrary to the fact that capillary action is ubiquitous in our daily lives, its role in drug delivery has not attracted attention. Therefore, its application in medicine and disease treatment has not been actively developed. This perspective begins by reviewing the principles, advantages, and limitations of the three existing drug delivery strategies: non-covalent interaction, cavity loading, and covalent conjugation. Then, we discussed the principle of capillary action in drug delivery and the influencing factors that determine its performance. To illustrate the advantages of capillary action over existing drug delivery strategies and how the capillary action could potentially address the shortcomings of the existing drug delivery strategies, we described five examples of using capillary action to design drug delivery platforms for disease treatment: marker pen for topical and transdermal drug delivery, microneedle patch with a sponge container for pulsatile drug delivery, core-shell scaffold for sustained release of growth factors, oral bolus for insulin delivery to the esophagus, and semi-hollow floating ball for intravesical and gastroprotective drug delivery. Each of the five drug delivery platforms exhibits certain unique functions that existing drug delivery technologies cannot easily achieve, hence expected to solve specific practical medical problems that are not satisfactorily resolved. As people pay more attention to capillary action and develop more drug delivery platforms, more unique functions and characteristics of capillary action in drug delivery will be explored. Thus, capillary action could become an important choice for drug delivery systems to improve therapeutic drug efficacy, treat diseases, and improve human health.

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Leveraging Electrostatic Interactions for Drug Delivery to the Joint

Cited by 15 publications

References 138 publications

Branched poly‐l‐lysine for cartilage penetrating carriers

Branched poly‐l‐lysine for cartilage penetrating carriers

Targeted and responsive biomaterials in osteoarthritis

Applications of capillary action in drug delivery

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