Spray-dried microparticles: a potential vehicle for oral delivery of vaccines

Chablani, Lipika; Tawde, Suprita A.; D’Souza, Martin J.

doi:10.3109/02652048.2011.651503

Cited by 38 publications

(21 citation statements)

References 31 publications

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“…As an example, lectin from the orange peel mushroom Aleuria aurantia has been demonstrated to bind with high affinity to α‐L‐fucose residues on M cells . Moreover, AAL‐coupled microspheres were found to display preferential binding to the Peyer's patches of the follicle‐associated epithelium of the intestine . In keeping with the above, prophylactic oral administration of AAL‐bearing microparticles containing antigenic material in the form of tumor cell lysate has been previously demonstrated to induce high antibody titers and retard tumor growth in mice inoculated with various cancer cell lines …”

Section: Discussionmentioning

confidence: 72%

Development of a M cell‐targeted microparticulate platform, BSK02™, for oral immunization against the ovarian cancer antigen, sperm protein 17

Mattila¹,

Mirandola²,

Chiriva‐Internati

2018

J Biomed Mater Res

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Although it only accounts for approximately 5% of all female cancer cases, ovarian cancer (OC) ranks as the fifth leading cause of death due to cancer in women. We have evaluated the potential of an orally administered microparticulate vaccine incorporating an immunodominant epitope peptide derived from the cancer/testis antigen sperm protein 17 (SP17) aberrantly expressed in OC, to retard the progression of the disease. The peptide antigen and the immune-stimulatory toll-like receptor 9 ligand CpG oligonucleotide were incorporated into spray dried microparticles composed of enteric and sustained release polymers together with the Aleuria aurantia lectin targeting microfold cells present in the gut-associated lymphoid tissue. These particles were administered via oral route to mice challenged week prior with SP17-expressing ID8 OC cells. Analysis of splenocytes harvested from vaccinated mice revealed strong activation of IFN-γ+/CD8+ lymphocytes in response to re-stimulation with the SP17 antigen. Moreover, vaccinated animals showed significant retardation of ascites/tumor volume in comparison to placebo-treated animals four weeks after the tumor challenge (p = 0.005). Taken together, our results suggest that vaccination against SP17 using orally administered microparticles could potentially be used as an effective consolidation strategy for OC patients with residual tumor or high probability for relapse following first-line treatments. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2018.

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Section: Discussionmentioning

confidence: 72%

Development of a M cell‐targeted microparticulate platform, BSK02™, for oral immunization against the ovarian cancer antigen, sperm protein 17

Mattila¹,

Mirandola²,

Chiriva‐Internati

2018

J Biomed Mater Res

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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%

“…This polymer was found to be a good candidate for controlled release of antigens and resulted in vibriocidal antibody titers. We prepared the particles utilizing this polymer along with other excipients by using an optimized microparticulate formula for oral vaccine delivery by spray drying [8]. To target our vaccine formulation to M-cells in the Peyer’s patches of the intestine, M-cell targeting agent, Aleuria aurantia lectin (AAL) was used in the formulation [9,10].…”

Section: Introductionmentioning

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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“…Langerhans cells are dendritic cells that activate T cells and induce a strong immune response and occupy around 20% of the skin's area. On the other hand, M-cells are the microfold cells, which act as sampling ports for any foreign entities encountered in the small intestine upon oral administration [18][19][20][21][22][23]. These M cells house various dendritic cells and immune cells in them.…”

Section: Introductionmentioning

confidence: 99%

“…The vaccine particles were administered for this purpose using a microneedle device called as AdminPen TM . For this purpose, microparticles were prepared by spray drying technique using methacrylic copolymer Eudragit ® FS 30 D and hydroxyl propyl methyl cellulose acetate succinate (HPMCAS) as described elsewhere [20,23]. These polymers have been reported their applications for transdermal delivery in form of patches as well as particulates [29,30].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of microparticulate ovarian cancer vaccine via transdermal route of delivery

Tawde¹,

Chablani

Akalkotkar

et al. 2016

Journal of Controlled Release

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Ovarian cancer is the fifth most commonly occurring malignancy in women, with the highest mortality rate among all the gynecological tumors. Microparticulate vaccine can serve as an immunotherapeutic approach with a promising antigenic delivery system without a need for conventional adjuvants. In this study, a microparticulate vaccine using whole cell lysate of a murine ovarian cancer cell line, ID8 was prepared by spray drying. Further, the effect of interleukins (ILs) such as IL-2 and IL-12 was evaluated in a separate study group by administering them with vaccine particles to enhance the immune response. The vaccine microparticles were administered to C57BL/6 female mice via transdermal alone and in combination with the oral route. The transdermal vaccine was delivered using a metallic microneedle device, AdminPen™. Orally administered microparticles also included an M-cell targeting ligand, Aleuria aurantia lectin, to enhance the targeted uptake from microfold cells (M-cells) in Peyer's patches of small intestine. In case of combination of routes, mice were given 5 transdermal doses and 5 oral doses administered alternatively, beginning with transdermal dose. At the end of vaccination, mice were challenged with live tumor cells. Vaccine alone resulted in around 1.5 times tumor suppression in case of transdermal and combination of routes at the end of 15th week when compared to controls. Inclusion of interleukins resulted in 3 times tumor suppression when administered with transdermal vaccine and around 9 times tumor suppression for the combination route of delivery in comparison to controls. These results were further potentiated by serum IgG, IgG1 and IgG2a titers. Moreover, CD8+ T-cell, CD4+ T-cell and NK (natural killer) cell populations in splenocytes were elevated in case of vaccinated mice. Thus, vaccine microparticles could trigger humoral as well as cellular immune response when administered transdermally and via combination of route of delivery. However overall, vaccine administered with interleukins, via combination of route, was found to be the most efficacious to suppress the tumor growth and lead to a protective immune response.

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Spray-dried microparticles: a potential vehicle for oral delivery of vaccines

Cited by 38 publications

References 31 publications

Development of a M cell‐targeted microparticulate platform, BSK02™, for oral immunization against the ovarian cancer antigen, sperm protein 17

Development of a M cell‐targeted microparticulate platform, BSK02™, for oral immunization against the ovarian cancer antigen, sperm protein 17

Formulation and evaluation of oral microparticulate ovarian cancer vaccines

Evaluation of microparticulate ovarian cancer vaccine via transdermal route of delivery

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