Sustained-release protamine sulphate-impregnated microspheres may reduce the frequent administration of recombinant interferon α-2b in ovarian cancer

Gulia, Monika; Rai, Shweta; Jain, Upendra Kumar; Katare, Om Prakash; Katyal, Anju; Madan, Jitender

doi:10.1097/cad.0000000000000026

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…The microencapsulation process achieved less than 60% encapsulation efficiency in several formulations [101,113], while a reduction in biological activity was observed in some cases [93,100,106]. In other formulations, the drug was released abruptly or incompletely [94,99,130].…”

Section: Ifn γmentioning

confidence: 98%

Forms and Methods for Interferon's Encapsulation

Ramos¹,

Villacis²,

Vispo³

et al. 2021

Preprint

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Interferons (IFNs) are cytokines involved in the immune response that act on innate and adaptive immunity. These proteins are natural cell-signaling glycoproteins expressed in response to viral infections, tumors, and biological inducers and constitute the first line of defense of vertebrates against infectious agents. They have been marketed for more than 30 years with considerable impact on the global therapeutic protein market thanks to their diversity in terms of biological activities. They have been used as single agents or with combination treatment regimens, demonstrating promising clinical results, resulting in 22 different formulations approved by regulatory agencies. The 163 clinical trials with currently active IFNs reinforce their importance as therapeutics for human health. However, their application has presented difficulties due to the molecules’ size, sensitivity to degradation, and rapid elimination from the bloodstream. For some years now, work has been underway to obtain new drug delivery systems to provide adequate therapeutic concentrations for these cytokines, decrease their toxicity and prolong their half-life in the circulation. Although different research groups have presented various formulations that encapsulate IFNs, to date, there is no formulation approved for use in humans. The current review exhibits an updated summary of all encapsulation forms presented in the scientific literature for these cytokines IFNα, IFNß, and IFNγ, from the year 1996 to the year 2021, considering parameters such as: encapsulating matrix, route of administration, and encapsulation.

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Section: Ifn γmentioning

confidence: 98%

Forms and Methods for Interferon's Encapsulation

Ramos¹,

Villacis²,

Vispo³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…In vivo assays in Sprague–Dawley rats of this formulation showed that plasma levels of the molecule were stable for 13 days, starting with a rapid release on the first day [ 132 ]. In 2014, Gulia et al impregnated protamine sulfate to gelatin microspheres to increase the release time of IFN-α to 336 h and prolong the in vitro cytotoxic effect on ovarian cancer SK-OV-3 cells [ 133 ]. Chen et al (2016) proposed a different structure by formulating chondroitin sulfate and PVP microneedles that had stability for two months and did not cause skin damage after subcutaneous administration in SD rats [ 134 ].…”

Section: Recent Encapsulation Forms Of Ifnsmentioning

confidence: 99%

“…Despite the positive results obtained in in vitro and in vivo studies of microencapsulations, none of them were evaluated in clinical trials except for Locteron, since they presented drawbacks at different levels. The microencapsulation process achieved less than 60% encapsulation efficiency in several formulations [ 130 , 136 ], while a reduction in biological activity was observed in some cases [ 119 , 129 , 133 ]. In other formulations, the drug was released abruptly or incompletely [ 120 , 128 , 141 ].…”

Section: Recent Encapsulation Forms Of Ifnsmentioning

confidence: 99%

Forms and Methods for Interferon’s Encapsulation

et al. 2021

View full text Add to dashboard Cite

Interferons (IFNs) are cytokines involved in the immune response that act on innate and adaptive immunity. These proteins are natural cell-signaling glycoproteins expressed in response to viral infections, tumors, and biological inducers and constitute the first line of defense of vertebrates against infectious agents. They have been marketed for more than 30 years with considerable impact on the global therapeutic protein market thanks to their diversity in terms of biological activities. They have been used as single agents or with combination treatment regimens, demonstrating promising clinical results, resulting in 22 different formulations approved by regulatory agencies. The 163 clinical trials with currently active IFNs reinforce their importance as therapeutics for human health. However, their application has presented difficulties due to the molecules’ size, sensitivity to degradation, and rapid elimination from the bloodstream. For some years now, work has been underway to obtain new drug delivery systems to provide adequate therapeutic concentrations for these cytokines, decrease their toxicity and prolong their half-life in the circulation. Although different research groups have presented various formulations that encapsulate IFNs, to date, there is no formulation approved for use in humans. The current review exhibits an updated summary of all encapsulation forms presented in the scientific literature for IFN-α, IFN-ß, and IFN-γ, from the year 1996 to the year 2021, considering parameters such as: encapsulating matrix, route of administration, target, advantages, and disadvantages of each formulation.

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“…On the other hand, the use of type-I IFN has been poorly effective, largely due to toxic effects. To overcome the systemic sideeffects, several IFN delivery systems have been developed, such as the conjugation with polyethylene glycol (PEG) [13,19], gene delivery by albumin fusion protein [20], and microspheres for a constant release [21,22].…”

Section: Introductionmentioning

confidence: 99%

A site-selective hyaluronan-interferonα2a conjugate for the treatment of ovarian cancer

Montagner

Merlo

Carpanese

et al. 2016

Journal of Controlled Release

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While interferon alpha (IFNα) is used in several viral and cancer contexts, its efficacy against ovarian cancer (OC) is far from being incontrovertibly demonstrated and, more importantly, is hindered by heavy systemic side effects. To overcome these issues, here we propose a strategy that allows a targeted delivery of the cytokine, by conjugating IFNα2a with an aldehyde-modified form of hyaluronic acid (HA). The resulting HA-IFNα2a bioconjugate was biochemically and biologically characterized. The conjugation with HA did not substantially modified both the antiviral function and the anti-proliferative activity of the cytokine. Moreover, the induction of STAT1 phosphorylation and of a specific gene expression signature in different targets was retained. In vivo optical imaging biodistribution showed that the i.p.-injected HA-IFNα2a persisted into the peritoneal cavity longer than IFNα2a without being toxic for intraperitoneal organs, thus potentially enhancing the loco-regional therapeutic effect. Indeed, in OC xenograft mouse models bioconjugate significantly improved survival as compared to the free cytokine. Overall, HA-IFNα2a bioconjugate disclosed an improved anticancer efficacy, and can be envisaged as a promising loco-regional treatment for OC.

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Sustained-release protamine sulphate-impregnated microspheres may reduce the frequent administration of recombinant interferon α-2b in ovarian cancer

Cited by 5 publications

References 29 publications

Forms and Methods for Interferon's Encapsulation

Forms and Methods for Interferon's Encapsulation

Forms and Methods for Interferon’s Encapsulation

A site-selective hyaluronan-interferonα2a conjugate for the treatment of ovarian cancer

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