Protective interactive noncondensing (PINC) polymers for enhanced plasmid distribution and expression in rat skeletal muscle

Mumper, Russell J.; Wang, Jijun; Klakamp, Scott L.; Nitta, Hiro; Anwer, Khursheed; Tagliaferri, Frank; Rolland, Alain

doi:10.1016/s0168-3659(97)00215-0

Cited by 112 publications

(72 citation statements)

References 21 publications

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“…[17] PVP polymers possess a positive charge and form a stronger hydrogen bonding with DNA in water below pH 5.5. [31] Mumper et al [17] demonstrated that the reduction of EB-DNA complex fluorescence intensity by PVP aqueous solution at pH 4.0 reached 60%, suggesting that the quenching may occur when PVP forms a ternary complex with DNA and EB by the electrostatic, hydrogen bonding, and hydrophobic interactions. In our work, the slight quenching of the EB fluorescence intensity by PVP in Tris-HCl buffer (pH 7.4) suggests that PVP interacts with DNA mainly via hydrogen bonding and hydrophobic interactions.…”

Section: Eb Quenching Experimentsmentioning

confidence: 99%

“…On the basis of the fact that the z potential of PVP is approximately 0 mV in salt solution, [17] the interaction modes between the copolymer and DNA can include hydrogen bonding, hydrophobic interaction, and indole residues' stacking. The interactions, in turn, promote shielding of the negatively charged phosphate groups, resulting in an increase in the surface charge of DNA.…”

Section: Z Potential Determinationmentioning

confidence: 99%

“…[12][13][14][15][16] Recently, PVP, as a potential booster of the gene expression using the naked DNA, was explored, and the results demonstrated that PVP can enhance the gene expression of the naked DNA in tissues. [17][18][19] These non-ionic polymers improve the gene expression most likely through non-condensing DNA and facilitate the transport of the gene into the cell. [9] In a previous study, we demonstrated that amphiphilic PVP copolymer P(NVP-co-TrpAMT) can destabilize the double strands (dsDNA) and enhance the amplification of the polymerase chain reaction (PCR).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of complexation of PVP copolymer with DNA

Zhang

Liang

Meng

et al. 2008

Polymers for Advanced Techs

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Interactions of amphiphilic copolymer poly (N-vinylpyrrolidone-co-N-t-Boc-tryptophanamido-N(-methacrylthiourea) [P(NVP-co-TrpAMT)] and poly(N-vinylpyrrlidone) (PVP) with DNA were studied with the aim to understand the difference in their complexation efficiencies when considered as a potential non-viral delivery vector. Fluorescence spectroscopy, ethidium bromide (EB) quenching, z potential measurement, and agarose gel electrophoresis were all carried out in Tris-HCl (pH 7.4) solution to assess the degree of interaction between the (co)polymers P(NVP-co-TrpAMT) and DNA. All of these measurements show that the high affinity of the copolymer for DNA can be demonstrated. We also found that P(NVP-co-TrpAMT)-I (PVP/PTrpAMT molar ratio was 100:2.88) exhibited a high DNA cleavage activity and induced the supercoiled form of the plasmid cleavage in the nicked and linear forms.Moreover, P(NVP-co-TrpAMT)-I exhibited stronger affinity for DNA than PVP and P(NVP-co-TrpAMT)-II (PVP/ PTrpAMT molar ratio of 100:6.35). This phenomenon is believed to be related to the structure of TrpAMT and the hydrophobic nature of the copolymer. P(NVP-co-TrpAMT)-II with higher hydrophobic segments creates a strong hydrophobic interaction and induces a steric barrier which hinders their complexation with DNA. The study reveals important information about the inner mechanisms involved in the interaction of the PVP copolymer with DNA, which aids in the design of novel efficient non-ionic gene carriers.

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Section: Eb Quenching Experimentsmentioning

confidence: 99%

Section: Z Potential Determinationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterization of complexation of PVP copolymer with DNA

Zhang

Liang

Meng

et al. 2008

Polymers for Advanced Techs

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“…Purified plasmids were formulated at a concentration of 3 mg DNA/ml using a 5% PVP delivery system, as described previously. 8,39 Briefly, formulations were made by adding stock solutions in the following order: water, plasmid, polymer, and 5 M NaCl. The plasmid and PVP are allowed to incubate at room temperature for 15 minutes prior to adding salt or lactose for tonicity adjustment.…”

Section: Plasmid/pvp Formulationmentioning

confidence: 99%

Intramuscular delivery of antiangiogenic genes suppresses secondary metastases after removal of primary tumors

et al. 2004

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The success of surgery to remove primary tumors can be compromised by the subsequent outgrowth of metastases. It is recognized that primary tumors secrete antiangiogenic factors that suppress the outgrowth of their daughter metastases. In accord we show here that surgical removal of primary EL-4 lymphomas led to a marked decrease in the levels of circulating angiostatin and endostatin, and promoted the growth of distant nodular tumors. Expression vectors encoding angiostatin and endostatin, formulated with poly-N-vinyl pyrrolidone (PVP), were injected into the tibialis and gastrocnemia muscles, leading to expression of angiostatin and endostatin in muscle fibers. High levels of biologically active exogenous proteins were secreted into the circulation. Intramuscular gene therapy with angiostatin and endostatin plasmids significantly inhibited tumor vascularity and induced tumor cell apoptosis, and thereby suppressed the growth of secondary subcutaneous and disseminated metastatic tumors in the lung and liver. Simultaneous intramuscular delivery of both angiostatin and endostatin plasmids significantly prolonged the survival of mice after removal of primary tumors. These results suggest that intramuscular gene transfer of angiostatin and endostatin might serve as a prophylactic cancer-prevention strategy to combat the recurrence of cancer after surgical resection of primary tumors.

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“…This is perhaps surprising given that some polymers have been known to form hydrogen bonds with DNA and have been reported to be capable of enhancing gene delivery in their own right. 35 Therefore the current study is designed to determine the optimal polymer for delivery of nucleic acid cargo. Four different polymers were used to form dissolvable microneedles, loaded with or without nucleic acid cargo.…”

Section: Introductionmentioning

confidence: 99%

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

Cole

McCaffrey

Ali

et al. 2016

Human Vaccines & Immunotherapeutics

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DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application.

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Protective interactive noncondensing (PINC) polymers for enhanced plasmid distribution and expression in rat skeletal muscle

Cited by 112 publications

References 21 publications

Characterization of complexation of PVP copolymer with DNA

Characterization of complexation of PVP copolymer with DNA

Intramuscular delivery of antiangiogenic genes suppresses secondary metastases after removal of primary tumors

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation

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