Effect of Vitamin E TPGS on immune response to nasally delivered diphtheria toxoid loaded poly(caprolactone) microparticles

Somavarapu, Satyanarayana; Pandit, S.; Gradassi, G.; Bandera, M.; Ravichandran, Easwaran; Alpar, Oya

doi:10.1016/j.ijpharm.2005.03.029

Cited by 31 publications

(23 citation statements)

References 7 publications

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“…One potential solution to this problem is to select an agent for which there are a minimum of regulatory obstacles. Therefore, we used vaccination protocols in which two natural products (chitosan and vitamin E) were evaluated to determine their utility as adjuvants (2,8,25,36). Administration of the HC 50 domain of BoNT/A simultaneously with chitosan or with vitamin E (Fig.…”

Section: Vol 75 2007mentioning

confidence: 99%

Trivalent Vaccine against Botulinum Toxin Serotypes A, B, and E That Can Be Administered by the Mucosal Route

et al. 2007

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Most reports dealing with vaccines against botulinum toxin have focused on the injection route of administration. This is unfortunate, because a mucosal vaccine is likely to be more efficacious for patients and pose fewer risks to health care workers and to the environment. Therefore, efforts were made to generate a mucosal vaccine that provides protection against the botulinum serotypes that typically cause human illness (serotypes A, B, and E). This work demonstrated that carboxy-terminal peptides derived from each of the three serotypes were able to bind to and penetrate human epithelial barriers in vitro, and there was no cross inhibition of membrane binding and transcytosis. The three polypeptides were then tested in vivo as a trivalent vaccine that could be administered to mice by the intranasal route. The results indicated that the mucosal vaccine evoked high secretory titers of immunoglobulin A (IgA), as well as high circulating titers of IgG and IgA, and it also evoked a high level of resistance to challenge with toxin. The immunoglobulin responses and the levels of resistance to challenge were increased by coadministration of adjuvants, such as chitosan and vitamin E. At least three mechanisms were identified to account for the antibody-induced resistance: (i) blockade of toxin absorption across epithelial cells, (ii) enhanced clearance of toxin from the circulation, and (iii) blockade of toxin action at the neuromuscular junction. These results are a compelling demonstration that a mucosal vaccine against multiple serotypes of botulinum toxin has been identified.

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Section: Vol 75 2007mentioning

confidence: 99%

Trivalent Vaccine against Botulinum Toxin Serotypes A, B, and E That Can Be Administered by the Mucosal Route

et al. 2007

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“…In reference to nasal delivery, the use of TPGS as an adjuvant for the nasally administered diphtheria toxoid has been reported (99). The vaccine was loaded into poly(caprolactone) microspheres (PCL) with and without the inclusion of TPGS, and the incorporation of TPGS into the PCL microparticles did not compromise diphtheria toxin loading.…”

Section: Other Routes Of Delivery: Pulmonary and Nasalmentioning

confidence: 99%

Advances in the Use of Tocols as Drug Delivery Vehicles

Constantinides¹,

2006

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There has been increasing interest in recent years in the drug delivery applications of tocols and their derivatives. Their biocompatibility and potential to deliver both poorly soluble and water-soluble drugs make tocols attractive as drug delivery vehicles. This review article will focus primarily on topical, oral, and parenteral drug administration using tocols, although other routes of delivery such as pulmonary and nasal will also be discussed. After an overview of the tocol structures, physicochemical properties with emphasis on their solvent properties, functions, and metabolism, specific case studies will be discussed where tocols have been successfully used in topical, oral, and parenteral drug formulations and marketed drug products. Case studies will be extended to those where tocol-based formulations were administered pulmonarily and nasally. As more clinical data and marketed drug products emerge, the utility and therapeutic value of tocols will certainly increase.

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“…The structural conformation of CPGS was determined by 1 H NMR in CDCl 3 at 500 MHz (ACF500, Bruker). FT-IR spectroscopy (FTIR-8400, Shimadzu) was used to investigate functional groups present in the intermediate product VDS and the final product CPGS.…”

Section: Characterization Of Cpgsmentioning

confidence: 99%

“…1 TPGS, a watersoluble form of the lipophilic vitamin E, is formed by the esterification of vitamin E succinate with polyethylene glycol (PEG). Its chemical structure contains both a hydrophobic and hydrophilic moiety, making it similar to a conventional surfactant.…”

Section: Introductionmentioning

confidence: 99%

Potential use of cholecalciferol polyethylene glycol succinate as a novel pharmaceutical additive

Tan

Yung

2007

J Biomedical Materials Res

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D-alpha-tocopheryl polyethylene glycol succinate (TPGS) has been utilized in numerous drug delivery formulations in recent years. Because of its amphiphilic structure, it can be used as emulsifier and vehicle for lipid-based drug delivery formulations. It is also an effective P-glycoprotein (P-gp) inhibitor. However, TPGS represents only one of the surfactants in the class of "Vitamin-PEG" conjugated surfactants. To design a new adjuvant or additive, a conjugate made of vitamin D (cholecalciferol) and PEG-cholecalciferol polyethylene glycol succinate (CPGS) was synthesized via a two-step reaction. We hypothesized that CPGS may exhibit similar characteristics to TPGS, and thus the physicochemical properties as well as the anticancer properties of CPGS were studied. The results demonstrated that CPGS reduced the particle size and increased the encapsulation efficiency of the PLGA nanoparticles, indicating that CPGS may also have the emulsifier function similar to TPGS. The drug release profiles showed that the nanoparticles with CPGS additive had a lower initial burst and more sustained release pattern. In vitro testing with Caco-2 cells showed that CPGS could increase the cytotoxicity of DOX-loaded PLGA nanoparticles. Based on the rhodamine accumulation study, the increased cytotoxicity is possibly due to the P-gp inhibition by CPGS. From current results, the use of CPGS as an adjuvant is promising and may enhance the efficacy of the overall drug delivery system.

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Effect of Vitamin E TPGS on immune response to nasally delivered diphtheria toxoid loaded poly(caprolactone) microparticles

Cited by 31 publications

References 7 publications

Trivalent Vaccine against Botulinum Toxin Serotypes A, B, and E That Can Be Administered by the Mucosal Route

Trivalent Vaccine against Botulinum Toxin Serotypes A, B, and E That Can Be Administered by the Mucosal Route

Advances in the Use of Tocols as Drug Delivery Vehicles

Potential use of cholecalciferol polyethylene glycol succinate as a novel pharmaceutical additive

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