Role of a Novel Excipient Poly(Ethylene Glycol)-b-Poly(L-Histidine) in Retention of Physical Stability of Insulin in Aqueous Solutions

Taluja, Ajay; Bae, You Han

doi:10.1007/s11095-007-9270-z

Cited by 18 publications

(12 citation statements)

References 40 publications

(47 reference statements)

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“…The block copolymer, methoxy poly(ethylene glycol)- b -poly( l -histidine)-poly( l -phenylalanine), herein called PEG b PHF, is an amphoteric pH-sensitive polymer in which the imidazole ring has a lone electron pair on the unsaturated nitrogen of histidine [39,40]. The chemical structure of PEG b PHF used in this study was confirmed by 1 H NMR (Supplementary information Fig.…”

Section: Resultsmentioning

confidence: 99%

pH-sensitive oncolytic adenovirus hybrid targeting acidic tumor microenvironment and angiogenesis

Choi

Jung

Kasala

et al. 2015

Journal of Controlled Release

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Although oncolytic adenoviruses (Ads) are an attractive option for cancer gene therapy, the intravenous administration of naked Ad still encounters unfavorable host responses, non-specific interactions, and heterogeneity in targeted cancer cells. To overcome these obstacles and achieve specific targeting of the tumor microenvironment, Ad was coated with the pH-sensitive block copolymer, methoxy poly(ethylene glycol)-b-poly(l-histidine-co-l-phenylalanine) (PEGbPHF). The physicochemical properties of the generated nanocomplex, Ad/PEGbPHF, were assessed. At pH 6.4, GFP-expressing Ad/PEGbPHF induced significantly higher GFP expression than naked Ad in both coxsackie and adenovirus receptor (CAR)-positive and -negative cells. To assess the therapeutic efficacy of the Ad/PEGbPHF complex platform, an oncolytic Ad expressing VEGF promoter-targeting transcriptional repressor (KOX) was used to form complexes. At pH 6.4, KOX/PEGbPHF significantly suppressed VEGF gene expression, cancer cell migration, vessel sprouting, and cancer cell killing effect compared to naked KOX or KOX/PEGbPHF at pH 7.4, demonstrating that KOX/PEGbPHF can overcome the lack of CAR that is frequently observed in tumor tissues. The antitumor activity of KOX/PEGbPHF systemically administered to a tumor xenograft model was significantly higher than that of naked KOX. Furthermore, KOX/PEGbPHF showed lower hepatic toxicity and did not induce an innate immune response against Ad. Altogether, these results demonstrate that pH-sensitive polymer-coated Ad complex significantly increases net positive charge upon exposure to hypoxic tumor microenvironment, allowing passive targeting to the tumor tissue. It may offer superior potential for systemic therapy, due to its improved tumor selectivity, increased therapeutic efficacy, and lower toxicity compared to naked KOX.

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Section: Resultsmentioning

confidence: 99%

pH-sensitive oncolytic adenovirus hybrid targeting acidic tumor microenvironment and angiogenesis

Choi

Jung

Kasala

et al. 2015

Journal of Controlled Release

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“…However, insulin-chitosan PEC protects insulin from degradation for at least 24 h. Although high molecular weight chitosan and chitosan derivatives were found to enhance the thermal stability of insulin 37 , the effect of chitosan low molecular weight has yet to be investigated. The protective effect of PEC may be due to the reduction of aggregation and fibrillation of insulin as free insulin solution becomes turbid after 24 h. Other cationic polymers such as poly (ethylene glycol)-b-poly (L-histidine) that forms PEC with insulin reduce aggregation of insulin on agitation 38 . Consequently, one can assume that LMWC reduces insulin aggregations.…”

Section: Accelerated Stability Of Insulin-chitosan Pecmentioning

confidence: 99%

Insulin-chitosan polyelectrolyte _anocomplexes: preparation, characterization and stabilization of insulin

Elsayed¹,

Al-Remawi²,

Farouk³

et al. 2010

Sud Jnl Med Sci.

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Objectives: To formulate chitosan nanoparticles with specific combinations of molecular weight and degree of deacetylation (DDA) that could be developed into an oral insulin delivery system. Methods: This study was conducted at Jordanian Pharmaceutical Manufacturing Company (JPM), Jordan in the period 2006-2009. Nanoparticles were prepared by polyelectrolyte complexation method (PEC). The physicochemical characteristics of the nanoparticles were evaluated. The role of nanoparticles in stabilization of insulin at high temperature and protecting insulin from pancreatic degradation was investigated. Results: The PEC formation process is influenced by a variety of parameters, including the system pH, chitosan molecular weight and DDA. The most important factor appears to be the system pH. All insulin-chitosan complexes displayed positive zeta potential. PECs protect insulin from pancreatin and the protective ability affected by DDA of chitosan. The results of insulin stability indicate that insulin-chitosan PEC protects insulin from degradation for at least 24 h. Conclusions: Molecular parameters of chitosan nanoparticles play an important role in stabilization of insulin in the GIT. So we can modulate relative parameters to develop an oral insulin delivery system.

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“…The BSA or insulin concentration in the extracted solution was calculated using a BCA protein assay kit. In addition, circular dichroism (CD) analysis of insulin in the extracted solution at 4 h post-incubation performed using a J-815 CD spectrometer (Jasco International, UK) to evaluate the insulin stability [13]. inductively coupled plasma-atomic emission spectrometer [11].…”

Section: Recovery Of the Partially Uncapped Regions In The Liposomesmentioning

confidence: 99%

“…However, the insulin-loaded conventional liposomes (prepared via the rehydration of the lipid film using PBS containing insulin with sonication at 60 kHz) exhibited a significant reduction in the α-helix structure (Fig. 5e) [12,13] due to the harsh sonication conditions (i.e., the direct sonication of PBS containing labile proteins). These results emphasize the safe encapsulation of the proteins into the partially uncapped liposomes.…”

Section: Simple Encapsulation and Loading Efficiencymentioning

confidence: 99%

Facile synthesis of partially uncapped liposomes

Kwag

Park

Youn

et al. 2015

Colloids and Surfaces B: Biointerfaces

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Role of a Novel Excipient Poly(Ethylene Glycol)-b-Poly(L-Histidine) in Retention of Physical Stability of Insulin in Aqueous Solutions

Abstract: Understanding and manipulation of such polyelectrolyte-protein complexation will likely play a role in protein stabilization.

Cited by 18 publications

References 40 publications

pH-sensitive oncolytic adenovirus hybrid targeting acidic tumor microenvironment and angiogenesis

pH-sensitive oncolytic adenovirus hybrid targeting acidic tumor microenvironment and angiogenesis

Insulin-chitosan polyelectrolyte _anocomplexes: preparation, characterization and stabilization of insulin

Facile synthesis of partially uncapped liposomes

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