Lower-Sized Chitosan Nanocapsules for Transcutaneous Antigen Delivery

Abstract

Transcutaneous vaccination has several advantages including having a noninvasive route and needle-free administration; nonetheless developing an effective transdermal formulation has not been an easy task because skin physiology, particularly the stratum corneum, does not allow antigen penetration. Size is a crucial parameter for successful active molecule administration through the skin. Here we report a new core-shell structure rationally developed for transcutaneous antigen delivery. The resulting multifunctional carrier has an oily core with immune adjuvant properties and a polymeric corona made of chitosan. This system has a size of around 100 nm and a positive zeta potential. The new formulation is stable in storage and physiological conditions. Ovalbumin (OVA) was used as the antigen model and the developed nanocapsules show high association efficiency (75%). Chitosan nanocapsules have high interaction with the immune system which was demonstrated by complement activation and also did not affect cell viability in the macrophage cell line. Finally, ex vivo studies using a pig skin model show that OVA associated to the chitosan nanocapsules developed in this study penetrated and were retained better than OVA in solution. Thus, the physicochemical properties and their adequate characteristics make this carrier an excellent platform for transcutaneous antigen delivery.

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“…These characteristics facilitate the controlled release of the medicated NE particles from the gel matrix, hence allowing their penetration into the SC of the skin. 53 On the other hand, it can be seen that CEO-NE-based NFs' permeation across the skin was gradual. Such behavior could be explained on the basis of the low degradation rate of PVA NFs, which could increase the opportunity for drug deposition and retention in the skin and subsequently sustain its permeation.…”

“…Regarding CEO-NE-based NEG, the gel polymeric matrix played an important role due to their proper rheological property, bioadhesive and penetration enhancement characteristics (mainly CS) 53 as well as the antiinflammatory activity (particularly CS and GA), via downregulation of several inflammatory mediators including COX-2, that may act synergistically with that of CEO. [69][70][71][72][73] In case of CEO-NE-based NFs, until this moment, no articles were published concerning any anti-inflammatory activity for PVA.…”

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“…58,[60][61][62][63] These methods of delivery require use of adequate delivery devices, of which there are several in development. [64][65][66] Because of the similarity with human skin, the pig is often used as a nonclinical model for safety testing. 67 The pathologist should be aware of "dippity pig syndrome" that is characterized by reddened skin and open sores along the dorsum in healthy young pigs, which may overlap the region of dose administration and confound the toxicology interpretation ( Figure 1).…”

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“…Nanosystems were designed and developed based on a previous experimental design made by our research group using the solvent displacement technique [13,22]. The organic phase consisted of 10 mg of BKC, 60 or 120 mg of TCPH and 50 or 100 mg of LP-HCO plus organic solvents (750 µL ethanol and 4.25 mL of acetone).…”