Oral delivery of microparticles containing plasmid DNA encoding hepatitis-B surface antigen

Bhowmik, Tuhin; D'Souza, Bernadette; Uddin, Mohammad Nasir; D’Souza, Martin J.

doi:10.3109/1061186x.2012.662686

Cited by 28 publications

(12 citation statements)

References 40 publications

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“…Although many efforts have been put into the design and modification of chitosan nanoparticles, a viable oral delivery system for DNA vaccines is still lacking [33]. One major obstacle to achieving satisfactory oral vaccinations in the DNA degradation results when exposed to the acidic gastric environment and the subsequent decreased uptake via lymphoid tissue in the gastrointestinal tract [35,36,37]. We demonstrated here, that compared with plain chitosan nanoparticles, A.C.NPs protect DNA against degradation in stimulated gastric fluid (pH 1.5).…”

Section: Discussionmentioning

confidence: 99%

Alginic Acid-Coated Chitosan Nanoparticles Loaded with Legumain DNA Vaccine: Effect against Breast Cancer in Mice

Liu

et al. 2013

PLoS ONE

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Legumain-based DNA vaccines have potential to protect against breast cancer. However, the lack of a safe and efficient oral delivery system restricts its clinical application. Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs) as an oral delivery carrier for a legumain DNA vaccine. First, we tested its characteristic in acidic environments in vitro. DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5) than did chitosan nanoparticles (C.NPs). Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH. Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer’s patches. Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs. A.C.NPs loaded with empty plasmids served as a control. Oral vaccination was performed in the murine orthotopic 4T1 breast cancer model. Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers. Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl2, which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3+/CD8+/CD25+) when treated with A.C.NPs carriers compared with PBS C.NPs. Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine. Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.

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Section: Discussionmentioning

confidence: 99%

Alginic Acid-Coated Chitosan Nanoparticles Loaded with Legumain DNA Vaccine: Effect against Breast Cancer in Mice

Liu

et al. 2013

PLoS ONE

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“…Finally, the particles loaded with drugs obtained by spray-drying could be administered by different routes such as oral [127][128][129][130][131][132], pulmonary [12,23,82,133,134), ophthalmic [93,111,135], parenteral [22,38,136], nasal [60,120,121,137], and vaginal [138], stressing its great In vitro tests showed that their mucoadhesion was 2-fold higher than that of a hydroxyethylcellulose gel formulation [138].…”

Section: Different Routes Of Administration Of Drug-loaded Polymeric mentioning

confidence: 99%

Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers

Sosnik

Seremeta

2015

Advances in Colloid and Interface Science

523

252

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“…The vaccine formulation was prepared by spray drying technique [8–10,18–24]. Briefly, HPMCAS and Eudragit® FS 30D were dissolved in an alkaline solution, followed by addition of chitosan glycol.…”

Section: Methodsmentioning

confidence: 99%

Formulation and evaluation of oral microparticulate ovarian cancer vaccines

Tawde

Chablani

Akalkotkar

et al. 2012

Vaccine

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Ovarian cancer is the fifth most leading cause of cancer related deaths in women in the US. Customized immunotherapeutic strategies may serve as an alternative method to control the recurrence or progression of ovarian cancer and to avoid severe adverse effects of chemotherapy. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared with the use of a spray dryer. These particles were designed for oral delivery using enteric polymers such as methacrylic copolymer, Eudragit® FS30D and hydroxyl propyl methyl cellulose acetate succinate. These particles were targeted for uptake via microfold cell (M-cell) in Peyer\u27s patches of small intestine using M-cell targeting ligand, Aleuria aurantia lectin. The interleukins (ILs) such as IL-2 and IL-12 were added to the vaccine formulation to further enhance the immune response. The particles obtained were of 1.58 ± 0.62 μm size with a charge of 12.48 ± 2.32 mV. The vaccine efficacy was evaluated by administering the particles via oral route to C57BL/6 female mice. At the end of vaccination, mice were challenged with live tumor cells. Vaccinated mice showed significant (around six-fold) retardation of tumor volume in comparison to non-vaccinated animals for 3 weeks after the tumor challenge (p \u3c 0.001). The serum IgG antibody levels were found to be elevated in case of vaccinated animals in comparison to non-vaccinated group (p \u3c 0.05). Analysis of IgG1 titers (indicative of Th2 response) and IgG2a titers (indicative of Th1 response) showed a mixed Th1 and Th2 immune response in case vaccine alone and Th2 response in case of vaccine with interleukins group. Moreover, CD8+ T-cell, CD4+ T-cell and B-cell populations in different lymphatic organs were elevated in case of vaccinated mice. Thus, whole cell lysate vaccine microparticles formulated by spray drying could trigger humoral as well as cellular immune response when administered orally. Such vaccine could potentially be an effective treatment for patients with residual tumor or high tumor-relapse probability

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Oral delivery of microparticles containing plasmid DNA encoding hepatitis-B surface antigen

Cited by 28 publications

References 40 publications

Alginic Acid-Coated Chitosan Nanoparticles Loaded with Legumain DNA Vaccine: Effect against Breast Cancer in Mice

Alginic Acid-Coated Chitosan Nanoparticles Loaded with Legumain DNA Vaccine: Effect against Breast Cancer in Mice

Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers

Formulation and evaluation of oral microparticulate ovarian cancer vaccines

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