HPMC-p, an inert micronized powder form of hydroxy-propyl-methyl-cellulose, when insufflated nasally, provides a natural barrier against pollen allergens and noxious agents. This overview assesses the efficacy and safety of this patented powder product and delivery system without an analogue among the cellulose derivatives. Areas covered: Twenty-six studies with HPMC-p were critically appraised to obtain an updated characteristic of the product. Most studies assessed the efficacy of HPMC-p as a nasal barrier enforcing measure: one experimental setup evaluated its ability to prevent or delay the diffusion of allergen through it, two clinical studies used allergen provocation tests, and the remaining relied on clinical criteria in open real world or placebo controlled designs. Two studies checked if HPMC-p could enhance the efficacy of drugs applied nasally to treat local symptoms. The studies, using either nasal allergen challenge or natural exposure of patients to environmental allergen, support the hypothesis that HPMC-p possesses barrier enforcing properties. Also, acute and clinical experiments indicated that intra-nasal application of HPMC-p following local relief medications enhances their ability to suppress symptoms and reduces their long-term use. Expert commentary: Nasal insufflation of HPMC-p provides a mucosal barrier, reducing the nasal symptoms and enhancing the effects of local relief medications.