Development of PEGylated carboxylic acid-modified polyamidoamine dendrimers as bone-targeting carriers for the treatment of bone diseases

Yamashita, Shugo; Katsumi, Hidemasa; Hibino, Nozomi; Isobe, Yugo; Yagi, Yumiko; Kusamori, Kosuke; Sakane, Toshiyasu; Yamamoto, Akira

doi:10.1016/j.jconrel.2017.07.018

Cited by 51 publications

(28 citation statements)

References 30 publications

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“…Though the particles in the size range from 10 to 70 nm are known to penetrate very small capillaries including the lacuna of the bone tissue, 70 to 100 nm particles are generally used to target bone because of their extended blood circulation time [225,239]. In addition, a degradable carrier can improve the release kinetics of therapeutics and prevent the carrier accumulation through controlled degradation of their backbone [240][241][242][243][244][245][246][247][248][249][250].…”

Section: Assembly Of Bone-targeting Carriers-mentioning

confidence: 99%

Biomaterial-assisted local and systemic delivery of bioactive agents for bone repair

2019

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Although bone tissues possess an intrinsic capacity for repair, there are cases where bone healing is either impaired or insufficient, such as fracture non-union, osteoporosis, osteomyelitis, and cancers. In these cases, treatments like surgical interventions are used, either alone or in combination with bioactive agents, to promote tissue repair and manage associated clinical complications. Improving the efficacy of bioactive agents often requires carriers, with biomaterials being a pivotal player. In this review, we discuss the role of biomaterials in realizing the local and systemic delivery of biomolecules to the bone tissue. The versatility of biomaterials enables design of carriers with the desired loading efficiency, release profile, and on-demand delivery. Besides local administration, systemic administration of drugs is necessary to combat diseases like osteoporosis, warranting bone-targeting drug delivery systems. Thus, chemical moieties with the affinity towards bone extracellular matrix components like apatite minerals have been widely utilized to create bone-targeting carriers with better biodistribution, which cannot be achieved by the drugs alone. Bone-targeting carriers combined with the desired drugs or bioactive agents have been extensively investigated to enhance bone healing while minimizing off-target effects. Herein, these advancements in the field have been systematically reviewed.

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Section: Assembly Of Bone-targeting Carriers-mentioning

confidence: 99%

Biomaterial-assisted local and systemic delivery of bioactive agents for bone repair

2019

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“…Of the various strategies available, conjugation of drugs with targeting ligands via chemical modification appears to be a promising approach for renal drug targeting (4)(5)(6). However, chemically modified conjugates are generally distributed in the liver and spleen because of uptake by the reticuloendothelial system (7,8).…”

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confidence: 99%

l -Serine–modified polyamidoamine dendrimer as a highly potent renal targeting drug carrier

Matsuura

Katsumi

Suzuki

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Effective delivery of drug carriers selectively to the kidney is challenging because of their uptake by the reticuloendothelial system in the liver and spleen, which limits effective treatment of kidney diseases and results in side effects. To address this issue, we synthesized L-serine (Ser)-modified polyamidoamine dendrimer (PAMAM) as a potent renal targeting drug carrier. Approximately 82% of the dose was accumulated in the kidney at 3 h after i.v. injection of 111 In-labeled Ser-PAMAM in mice, while i.v. injection of 111 In-labeled unmodified PAMAM, L-threonine modified PAMAM, and L-tyrosine modified PAMAM resulted in kidney accumulations of 28%, 35%, and 31%, respectively. Single-photon emission computed tomography/computed tomography (SPECT/ CT) images also indicated that 111 In-labeled Ser-PAMAM specifically accumulated in the kidneys. An intrakidney distribution study showed that fluorescein isothiocyanate-labeled Ser-PAMAM accumulated predominantly in renal proximal tubules. Results of a cellular uptake study of Ser-PAMAM in LLC-PK1 cells in the presence of inhibitors [genistein, 5-(N-ethyl-N-isopropyl)amiloride, and lysozyme] revealed that caveolae-mediated endocytosis, micropinocytosis, and megalin were associated with the renal accumulation of Ser-PAMAM. The efficient renal distribution and angiotensinconverting enzyme (ACE) inhibition effect of captopril (CAP), an ACE inhibitor, was observed after i.v. injection of the Ser-PAMAM-CAP conjugate. These findings indicate that Ser-PAMAM is a promising renal targeting drug carrier for the treatment of kidney diseases. Thus, the results of this study demonstrate efficient renal targeting of a drug carrier via Ser modification.drug delivery | renal targeting | L-serine | dendrimer

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“…Second, osteoblasts preferentially bind to RGD. As the carbon terminal of RGD, Asp is necessary for bone affinity,42 and is involved in protein adsorption, MSC/osteoblast attachment, spreading, and proliferation 8…”

Section: Discussionmentioning

confidence: 99%

<p>Electrospun Poly (Aspartic Acid)-Modified Zein Nanofibers for Promoting Bone Regeneration</p>

Liu¹,

Miao²,

Qin³

et al. 2019

IJN

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BackgroundCritical-sized bone defects raise great challenges. Zein is of interest for bone regeneration, but it has limited ability to stimulate cell proliferation. In this regard, a poly (aspartic acid) (PAsp)-zein hybrid is promising, as PAsp can promote rat bone marrow stromal cell (rBMSCs) proliferation and osteogenic differentiation. This research aimed to develop electrospun PAsp-modified zein nanofibers to realize critical-sized bone defects repair.MethodsThree groups of PAsp-modified zein nanofibers were prepared, they were PAsp grafting percentages of 0% (zein), 5.32% (ZPAA-1), and 7.63% (ZPAA-2). Using rBMSCs as in vitro cell model and SD rats as in vivo animal model, fluorescence staining, SEM, CCK-8, ALP, ARS staining, μCT and histological analysis were performed to verify the biological and osteogenic activities for PAsp-modified zein nanofibers.ResultsAs the Asp content increased from 0% to 7.63%, the water contact angle decreased from 129.8 ± 2.3° to 105.5 ± 2.5°. SEM, fluorescence staining and CCK-8 assay showed that ZPAA-2 nanofibers had a superior effect on rBMSCs spreading and proliferation than did zein and ZPAA-1 nanofibers, ALP activity and ARS staining showed that ZPAA-2 can improve rBMSCs osteogenic differentiation. In vivo osteogenic activities was evaluated by μCT analysis, HE, Masson and immunohistochemical staining, indicating accelerated bone formation in ZPAA-2 SD rats after 4 and 8 weeks treatment, with a rank order of ZPAA-2 > ZPAA-1 > zein group. Moreover, the semiquantitative results of the Masson staining revealed that the maturity of the new bone was higher in the ZPAA-2 group than in the other groups.ConclusionElectrospun PAsp-modified zein can provide a suitable microenvironment for osteogenic differentiation of rBMSCs, as well as for bone regeneration; the optimal membrane appears to have a PAsp grafting percentage of 7.63%.

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Development of PEGylated carboxylic acid-modified polyamidoamine dendrimers as bone-targeting carriers for the treatment of bone diseases

Cited by 51 publications

References 30 publications

Biomaterial-assisted local and systemic delivery of bioactive agents for bone repair

Biomaterial-assisted local and systemic delivery of bioactive agents for bone repair

l -Serine–modified polyamidoamine dendrimer as a highly potent renal targeting drug carrier

<p>Electrospun Poly (Aspartic Acid)-Modified Zein Nanofibers for Promoting Bone Regeneration</p>

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