The Mucoadhesive Nanoparticle-Based Delivery System in the Development of Mucosal Vaccines

Abstract

Mucosal tissue constitutes the largest interface between the body and the external environment, regulating the entry of pathogens, particles, and molecules. Mucosal immunization is the most effective way to trigger a protective mucosal immune response. However, the majority of the currently licensed vaccines are recommended to be administered by intramuscular injection, which has obvious shortcomings, such as high production costs, low patient compliance, and lack of mucosal immune response. Strategies for eliciting mucosal and systemic immune responses are being developed, including appropriate vaccine adjuvant, delivery system, and bacterial or viral vectors. Biodegradable mucoadhesive nanoparticles (NPs) are the most promising candidate for vaccine delivery systems due to their inherent immune adjuvant property and the ability to protect the antigen from degradation, sustain the release of loaded antigen, and increase the residence time of antigen at the administration site. The current review outlined the complex structure of mucosa, the mechanism of interaction between NPs and mucosa, factors affecting the mucoadhesion of NPs, and the application of the delivery system based on mucoadhesive NPs in the field of vaccines. Moreover, this review demonstrated that the biodegradable and mucoadhesive NP-based delivery system has the potential for mucosal administration of vaccines.

Understanding Mucosal Physiology and Rationale of Formulation Design for Improved Mucosal Immunity

“…Polymeric nano/ microcarriers have better access to immunological compartments in Peyer's patches than soluble vaccines, which can boost mucosal vaccination immune responses. 117,118 There are few polymers that have been used for developing the formulations for mucosal immunity including poly-(lacticcoglycolic acid) (PLGA), chitosan, and poly(acrylic acid) (PAA). PLGA is a FDA (U.S. Food and Drug Adminstration) approved biodegradable that has been widely used as a carrier for DDS.…”

“…PLGA polymer nanoparticles are used for mucosal nasal vaccine delivery system, and when surface charged modification of PLGA is used for vaccine delivery, it showed sustained release and better immune response for mucosa. 118,119 PLGA as a carrier offers a versatile platform for mucosal vaccine delivery including sustained antigen release, enhanced adhesion to the mucosal surface, facilitation of targeted delivery to specific immune cell populations, and the potential to exhibit adjuvant effects. These combined attributes position PLGA nanoparticles as a valuable platform for developing nextgeneration mucosal vaccines.…”

“…Polymeric nano/microparticles for mucosal vaccine delivery play an important role because they deliver vaccines to a specific target site, control vaccine release in mucosal sites, protect vaccines from harsh gastric pH, digestive enzymes, and bile juices in the gastrointestinal (GI) tract, and are easy to modify to meet physicochemical properties. Polymeric nano/microcarriers have better access to immunological compartments in Peyer’s patches than soluble vaccines, which can boost mucosal vaccination immune responses. , There are few polymers that have been used for developing the formulations for mucosal immunity including poly(lacticcoglycolic acid) (PLGA), chitosan, and poly(acrylic acid) (PAA). PLGA is a FDA (U.S. Food and Drug Adminstration) approved biodegradable that has been widely used as a carrier for DDS.…”

Biomaterials-Enhanced Intranasal Delivery of Drugs as a Direct Route for Brain Targeting

“…Drug-loaded polymer microparticles, having sizes larger than 500 nm, are a suboptimal choice for IN drug delivery, as they are unable to diffuse through the smaller nanometric pores of the mucus layer ( Figure 6 ). However, muco-adhesive microparticle with sizes in the 500 nm–10 µm range, escaping the filtration by the nasal vestibule, have been proposed for IN drug delivery, exploiting their ability to bind to the mucus layer [ 44 , 45 ]. Their drug delivery efficiency depends on the ability of loaded drugs to diffuse through the microparticles and the nasal mucus layer, reaching the nasal epithelium in a shorter time than that required for muco-ciliary clearance.…”

“…On the other hand, drug-loaded nanoparticles are more advantageous than microparticles, due to their ability to penetrate and diffuse through the nasal mucus ( Figure 6 ), and to support all the subsequent phases of drug transport to the brain, previously described in Section 3 . Muco-adhesive nanoparticles have been frequently proposed for IN drug delivery, as they attach to the nasal mucus after administration, decreasing the possibility for their loss in the respiratory and digestive tracts [ 45 , 46 ]. On the other hand, muco-adhesive nanoparticles show limited drug delivery efficiency: as they slowly diffuse across the mucus layer, they are partially lost during the muco-ciliary clearance mechanism.…”