A crosslinked dextran sulfate-chitosan nanoparticle for delivery of therapeutic heparin-binding proteins

Guarino, Victoria A.; Blau, Adam; Alvarenga, Jack; Loscalzo, Joseph

doi:10.1016/j.ijpharm.2021.121287

Cited by 7 publications

(4 citation statements)

References 29 publications

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“…A concentration of 5 µg/mL chondroitin sulphate was required to achieve the equivalent inhibitory effect on transfection efficiency and GFP production of dextran sulphate at a concentration of 0.5 µg/mL. Whilst the sulphur content of the heparin used in this experiment was not tested by the supplier, heparin from porcine intestinal mucosa is reported to have a sulphur content of 11.3%–12.4% ( Aviezer et al, 1994 ; Landau et al, 2001 ; Ziegler and Seelig, 2008 ; Guarino et al, 2021 ). The overall sulphation density of the species investigated was therefore: dextran sulphate > heparin > chondroitin sulphate > dextran and the sulphation density was found to be directly proportional to the potency of inhibition on transfection performance.…”

Section: Resultsmentioning

confidence: 99%

Degradation of specific glycosaminoglycans improves transfection efficiency and vector production in transient lentiviral vector manufacturing processes

Williams-Fegredo,

Davies,

Knevelman

et al. 2024

Front. Bioeng. Biotechnol.

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Both cell surface and soluble extracellular glycosaminoglycans have been shown to interfere with the exogenous nucleic acid delivery efficiency of non-viral gene delivery, including lipoplex and polyplex-mediated transfection. Most gene therapy viral vectors used commercially and in clinical trials are currently manufactured using transient transfection-based bioprocesses. The growing demand for viral vector products, coupled with a global shortage in production capability, requires improved transfection technologies and processes to maximise process efficiency and productivity. Soluble extracellular glycosaminoglycans were found to accumulate in the conditioned cell culture medium of suspension adapted HEK293T cell cultures, compromising transfection performance and lentiviral vector production. The enzymatic degradation of specific, chondroitin sulphate-based, glycosaminoglycans with chondroitinase ABC was found to significantly enhance transfection performance. Additionally, we report significant improvements in functional lentiviral vector titre when cultivating cells at higher cell densities than those utilised in a control lentiviral vector bioprocess; an improvement that was further enhanced when cultures were supplemented with chondroitinase ABC prior to transfection. A 71.2% increase in functional lentiviral vector titre was calculated when doubling the cell density prior to transfection compared to the existing process and treatment of the high-density cell cultures with 0.1 U/mL chondroitinase ABC resulted in a further 18.6% increase in titre, presenting a method that can effectively enhance transfection performance.

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Section: Resultsmentioning

confidence: 99%

Degradation of specific glycosaminoglycans improves transfection efficiency and vector production in transient lentiviral vector manufacturing processes

Williams-Fegredo,

Davies,

Knevelman

et al. 2024

Front. Bioeng. Biotechnol.

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“…Hydrogels produced using amine aldehyde chemistry have been widely characterized and demonstrated to have favorable biocompatibility profiles [47][48][49][50]. By utilizing amines in hydrogel precursors, it is possible to augment small molecules, peptides, or proteins via Schiff base chemistry [51]. For instance, extracellular matrix molecules known to promote cellular attachment and survival can be readily incorporated.…”

Section: Discussionmentioning

confidence: 99%

Development of self-healing hydrogels to support choroidal endothelial cell transplantation for the treatment of early age related macular degeneration

Pandala,

Han,

Tobin

et al. 2024

Preprint

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In retinal diseases such as age-related macular degeneration (AMD) and choroideremia, a key pathophysiologic step is loss of endothelial cells of the choriocapillaris, the dense vascular bed required for maintaining health and function of the retina. As such, repopulation of choroidal vasculature early in the disease process may halt disease progression. Prior studies have shown that injection of donor cells in suspension results in significant cellular efflux and poor cell survival. As such, the goal of this study was to develop a hydrogel system designed to support CEC transplantation. A library of hydrogels was synthesized using laminin (i.e., LN111, LN121, and LN421), carboxy methyl chitosan, and oxidized dextran via reversible Schiff base chemistry. Each of the developed hydrogels was readily injectable into the suprachoroidal space, with excellent gelation, mechanical, and degradation properties. Laminin-based hydrogels were compatible with immortalized CEC survival in vitro, and suprachoroidal injection of LN111 and LN121 containing gels were well-tolerated in an in vivo rat model, whereas LN421 containing gels caused significant chorioretinal inflammation. Hydrogels were detected in the suprachoroidal space of immunosuppressed rats at 1-week post-injection and were completely resorbed by 1-month post-injection. There were significantly more CECs retained in immunosuppressed rats that received cell laden hydrogels than those that received unsupported cell suspensions (i.e., CECs only). These findings pave the way for future CEC replacement studies in animal models of choroidal cell loss toward the development of future therapies.Statement of significanceAge related macular degeneration (AMD) is a leading cause of untreatable blindness in the industrial world. A key pathologic step in AMD is loss of the choriocapillaris endothelial cells, which provide vascular support to the overlying retina, including the light-sensing photoreceptors. We believe that choroidal cell replacement early in disease may prevent retinal cell death and subsequent vision loss. In this study, we present a strategy for repopulating the choriocapillaris using choroidal endothelial cell laden hydrogels. Specifically, we demonstrate the synthesis and characterization of 3 different laminin-based hydrogel systems. LN111 and LN121 hydrogels were found to increase retention of choroidal endothelial cells following suprachoroidal transplantation. These findings pave the way for future cell replacement studies in animal models of choroidal cell dropout.

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“…Производные декстрана широко использовались в качестве носителей ФАВ [7][8][9][10]. В настоящее время установлено, что натриевая соль декстрансульфокислоты (ДСК) усиливает антивирусную активность белка интерферона, а также является мощным и селективным ингибитором различных оболочечных вирусов in vitro, таких как ретро-, герпес-, парамиксовирусы и др.…”

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Polymer Complexes of Amikacin with Sulfur-Containing Polymers

Semina,

Smirnova,

Solovskij

2024

A&Ch

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Химия полимерных лекарственных препаратов, интенсивно развивающаяся область науки, позволила осуществить прорыв в лечении наиболее опасных вирусных и онкологических заболеваний. В соответствии с классической теорией, предложенной Х. Рингсдорфом в середине 1980-х годов, физиологически активные полимеры (ФАП) прививочного типа синтезируют путём присоединения физиологически активного вещества (ФАВ) к инертному полимеру -носителю гидролизуемой химической связью. В условиях организма ФАВ выделяется в неизменном виде при гидролизе, а носитель, или продукты его деградации, выводятся, в большинстве случаев через почки за счёт клубочковой фильтрации. Этот подход помог решить множество задач в фармакологии, включая повышение терапевтического эффекта за счёт увеличения локальных концент-

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A crosslinked dextran sulfate-chitosan nanoparticle for delivery of therapeutic heparin-binding proteins

Cited by 7 publications

References 29 publications

Degradation of specific glycosaminoglycans improves transfection efficiency and vector production in transient lentiviral vector manufacturing processes

Degradation of specific glycosaminoglycans improves transfection efficiency and vector production in transient lentiviral vector manufacturing processes

Development of self-healing hydrogels to support choroidal endothelial cell transplantation for the treatment of early age related macular degeneration

Polymer Complexes of Amikacin with Sulfur-Containing Polymers

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