Biocompatibility and biodegradation of different hyaluronan derivatives (Hyaff) implanted in rats

Benedetti, L.; Cortivo, Roberta; Berti, T; Berti, Andrea; Pea, Federico; Mazzo, M; Moras, Maria Luisa; Abatangelo, Giovanni

doi:10.1016/0142-9612(93)90160-4

Cited by 199 publications

(119 citation statements)

References 23 publications

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“…Hence, to assess the therapeutic potential of low-molecular-weight polymers for CPT and DOX delivery with a degradable polymer, the drugs were conjugated to another 10 kDa polymer, one which is biocompatible, biodegradable [24,[36][37][38], and possesses tumor-targeting abilities; that is, hyaluronic acid (HA). We have previously reported that the combination's synergy can be retained through conjugation to high-molecular-weight 250 kDa HA, and we applied the same reaction schemes here to synthesize 10 kDa CPT-HA-DOX [20].…”

Section: Cpt and Dox Co-conjugated To Hamentioning

confidence: 99%

“…Here, we extend our approach to low-molecular-weight 10 kDa HA and poly(vinyl alcohol) (PVA) drug conjugates with various linker chemistries for the concurrent treatment of CPT and DOX. HA represents a biopolymer with high biocompatibility and active tumor-targeting capabilities [24][25][26][27], PVA is an archetypal nonbiodegradable polymer, and both have been found to passively accumulate in tumor tissue via the enhanced permeation and retention effect [3,28].…”

mentioning

confidence: 99%

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Low-Molecular-Weight Polymer–Drug Conjugates for Synergistic Anticancer Activity of Camptothecin and Doxorubicin Combinations

Camacho

Menegatti

Mitragotri

2016

Nanomedicine (Lond.)

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Background: High-molecular-weight (MW) polymers (>50,000 Da) can be conjugated to chemotherapy drugs in order to improve their tumor accumulation, while low MW polymers ≤10,000 Da are often overlooked due to faster plasma clearance. Small polymers, however, may facilitate deeper tumor penetration. Materials & methods:Here, we investigate the anticancer efficacy of 10 kDa hyaluronic acid or poly(vinyl alcohol) conjugated to synergistic combinations of camptothecin and doxorubicin, with emphasis on chemical linker impacts. Results: Our results emphasize drug hydrolyzability for synergy preservation, and also demonstrate superior cancer cell inhibition with low MW polymer-drug conjugates. Conclusion: This study shows the high therapeutic potential of low MW polymer-drug conjugates for polychemotherapy delivery, and provides further insight into the development of polymer-drug therapeutics.

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Section: Cpt and Dox Co-conjugated To Hamentioning

confidence: 99%

mentioning

confidence: 99%

Low-Molecular-Weight Polymer–Drug Conjugates for Synergistic Anticancer Activity of Camptothecin and Doxorubicin Combinations

Camacho

Menegatti

Mitragotri

2016

Nanomedicine (Lond.)

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“…The conversion of HA carboxyl groups into less hydrophilic esters represents a strategy to decrease the water solubility of HA, with the aim to reduce its susceptibility to HYAL degradation and enhance its in situ permanence time [46]. A well-known biopolymer synthetized to this end is HA benzylester (HYAFF 11), whose properties are finely regulated by its degree of functionalization [36,170].…”

Section: Modification Of Ha Carboxyl Groupsmentioning

confidence: 99%

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Fallacara¹,

Baldini²,

Manfredini³

et al. 2018

Preprint

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Since its first isolation in 1934, hyaluronic acid (HA) has been studied across a variety of research areas. This unbranched glycosaminoglycan consisting of repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronic acid is almost ubiquitary in humans and in other vertebrates. HA is involved in many key processes -including cell signaling, wound reparation, tissue regeneration, morphogenesis, matrix organization and pathobiology-, and has unique physico-chemical properties -such as biocompatibility, biodegradability, mucoadhesivity, hygroscopicity and viscoelasticity. For these reasons, exogenous HA has been investigated as drug delivery system and treatment in cancer, ophthalmology, arthrology, pneumology, rhinology, urology, aesthetic medicine and cosmetic. To improve and customize its properties and applications, HA can be subjected to chemical modifications: conjugation and crosslinking. The present review gives an overview regarding HA, describing its history, physico-chemical, structural and hydrodynamic properties, and biology -occurrence, biosynthesis (by hyaluronan synthases), degradation (by hyaluronidases and oxidative stress), roles, mechanisms of action and receptors. Furthermore, both conventional and recently emerging methods developed for the industrial production of HA and its chemical derivatization are presented. Finally, the medical, pharmaceutical and cosmetic applications of HA and its derivatives are reviewed, reporting examples of HA-based products which currently are on the market or are undergoing further investigations.

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“…By chemical modification of the free carboxyl groups on the glucuronic acid component of the hyaluronan chain it has been clearly demonstrated that the solubility of the hyaluronan molecule is drastically reduced such that it is solid even after extended periods in aqueous environments (Iannace et al, 1992). Furthermore, by varying the degree of carboxyl modification, the degradation rate can be tailored to meet the requirements of the implantation site and application (Benedetti et al, 1993). It has been demonstrated in many studies that benzyl esterification of the carboxyl groups results in non-toxic degradation products (Cortivo et al, 1991;Hume et al, 1992), including free hyaluronan, which is highly angiogenic (Montesano et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Induction of adipose tissue regeneration by chemically-modified hyaluronic acid

Rhodes

Bartolo

Bellini

et al. 2008

IJNBM

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Abstract:Hyaluronan was modified by amidation of the carboxyl groups with dodycyl amides to produce a viscous gel (HYADD3). Small aliquots were implanted intramuscularly in Wistar rats at a concentration of 30 mg/ml for up to 12 weeks. Standard histology and immunohistochemistry demonstrated low levels of inflammation at all time periods, absence of any fibrous capsule coupled with the presence of mature adipocytes within the degrading gel. It is concluded that the chemical architecture of HYADD3 gel causes the de novo regeneration of soft tissue by recruitment of appropriate progenitor cells.

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Biocompatibility and biodegradation of different hyaluronan derivatives (Hyaff) implanted in rats

Cited by 199 publications

References 23 publications

Low-Molecular-Weight Polymer–Drug Conjugates for Synergistic Anticancer Activity of Camptothecin and Doxorubicin Combinations

Low-Molecular-Weight Polymer–Drug Conjugates for Synergistic Anticancer Activity of Camptothecin and Doxorubicin Combinations

Hyaluronic Acid in the 3<sup>rd</sup> Millennium

Induction of adipose tissue regeneration by chemically-modified hyaluronic acid

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