Vaccination is an effective approach to prevent the consequences of infectious diseases. Vaccines strengthen immunity and make individuals resistant to infections with pathogens. Although conventional vaccines are highly immunogenic, they are associated with some safety issues. Subunit vaccines are safe, but they require adjuvants to stimulate the immune system because of their weaker immunogenicity. Adjuvants are entities incorporated into vaccines to increase the immunogenic responses of antigens. They play a crucial role in increasing the potency and efficacy of vaccines. Different adjuvants have different modes of action; therefore, a better understanding of their immunology could provide guidance for the development of novel adjuvants. Numerous studies have been conducted using different types of adjuvants to characterize their potency and safety; however, in practice, only few are used in human or animal vaccines. This review aims to introduce the different modes of action of adjuvants and give insight into the types of adjuvants that possess the greatest potential for adjuvanticity.

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BackgroundBuccal delivery of insulin is still a challenging issue for the researchers due to the presence of permeability barrier (buccal mucosa) in the buccal cavity. The main objective of this study was to investigate the safety, effectiveness, and potential of various liposomes containing different bile salts to improve the permeation of insulin across in vitro TR146 buccal cell layers.MethodsElastic bilosomes containing soy lecithin and bile salt edge activators (sodium cholate [SC], sodium taurocholate [STC], sodium glycocholate [SGC], sodium deoxyglycocholate [SDGC], or sodium deoxytaurocholate [SDTC]) were fabricated by thin-film hydration method. The prepared liposomes were characterized, and in vitro permeation studies were performed. The fluorescein isothiocyanate-insulin-loaded elastic bilosomes were used to evaluate the quantitative and qualitative cellular uptake studies.ResultsThe prepared elastic bilosomes had a particle size and an entrapment efficiency of ~140–150 nm and 66%–78%, respectively. SDGC-lipo (SDGC-incorporated liposome) was observed to be the most superior with an enhancement ratio (ER) of 5.24 (P<0.001). The SC-incorporated liposome (SC-lipo) and SDTC-incorporated liposome (SDTC-lipo) also led to a significant enhancement with ERs of 3.20 and 3.10 (P<0.05), respectively, compared with insulin solution. These results were further supported by quantitative and qualitative cellular uptake studies performed employing fluorescence-activated cell sorting analysis and confocal microscopy, respectively. The relative median fluorescence intensity values of elastic bilosomes were counted in the order of SDGC-lipo > SC-lipo > SDTC-lipo > SGC-incorporated liposome > STC-incorporated liposome, and similarity in the permeability profile of the employed elastic bilosomes was noted.ConclusionThis study presents the employment of various derivatives of cholic acid-loaded elastic bilosomes as a promising strategy to enhance the permeation of insulin through buccal route.

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Transdermal drug administration presents several advantages and it is therefore favorable as an alternative drug delivery route. However, transdermal delivery of biopharmaceutical drugs is made difficult by the skin barrier. Microneedle application and iontophoresis are strategies which can be used to overcome this barrier. Therefore, recombinant human growth hormone (rhGH) was used as a model macromolecular drug and was transdermally delivered using microneedle application and iontophoresis. Methylene blue staining, stereomicroscopy and scanning electron microscope (SEM) imaging were used to characterize the microchannels produced. To optimize the iontophoresis protocol, the effects of molecular charge and current density on transdermal delivery were evaluated in an in vitro permeation study using excised rat skin tissues. Using the optimized iontophoresis protocol, the combination effects of iontophoretic delivery via microchannels were evaluated in three different experimental designs. The flux obtained with anodal iontophoresis in citrate buffer was approximately 10-fold higher that that with cathodal iontophoresis in phosphate buffered saline (PBS). Flux also increased with current density in anodal iontophoresis. The combination of iontophoresis and microneedle application produced higher flux than single application. These results suggest that anodal iontophoresis with higher current density enhances the permeation of macromolecules through microchannels created by microneedles. In conclusion, the combination of iontophoresis and microneedles is a potential strategy for the enhancement of transdermal delivery of macromolecular drugs.