burst release may occur due to rigidity and less flexibility in shape. nanostructured lipid carriers (nlc) are synthesized by a mixture of solid and aqueous lipids. nlc's are developed from slns, thus referred to as second generation lnps. intranasal administration of nlc loaded with curcumin (crm) increased biodistribution and concentration in brain after emerging as a potential system for brain cancer. small colloidal systems made of micelles containing oil, aqueous phases, and emulsifiers are called nanoemulsions. intranasal delivery of gel nanoemulsion loaded with temozolomide is observed to exhibit sustained release and better permeation from nose to brain to treat glioblastoma. polymer-based nanoparticles depiction of a type of polymer-based nanoparticle. nanospheres contain a uniformly dispersed drug encapsulated in a polymeric core and matrix. depiction of a polymer-based nanoparticle. nanocapsules consist of drugs encapsulated in a polymeric membrane. polymer-based nanoparticles can be made from either natural or synthetic sources. nanospheres and nanocapsules are polymeric nanoparticle systems. natural polymers can be found in the environment or human body. on the other hand, synthetic polymers do not occur naturally and are artificially developed polymers with chemical modifications. natural polymer-based nanoparticles can be made up of chitosan, hyaluronic acid, alginate, and gelatin. natural polymers exhibit excellent biocompatibility and biodegradability, and low toxicity. synthetic polymer-based nanoparticles can comprise of poly (glycolic acid) (pga), poly (lactic acid) (pla), and poly(l-lactide-co-glycolide) (plga). a study evaluated chitosan nanoparticles loaded with an anti-epileptic drug, phenytoin (pht), to treat epilepsy. observations suggested high stability, sustained release, and bioavailability when these particles where administered via the intranasal route. similarly, administering plga nanoparticles loaded lamotrigine (ltg), polymer-based nanoparticle, showed better permeation through bbb and higher bioavailability. exosomes depiction of exosome formation. following invagination of the plasma membrane, multivesicular bodies (mvbs) form and fuse with membrane to release exosomes. exosomes are vesicular structures containing genetic information. recently, exosomes are being utilized as drug carriers. these systems are observed to be stable, specific, and safe. moreover, delivery of exosomes shows less immunogenic affects. further surface modifications and conjugation with liposomes enhances the therapeutic effects. based on a previous study, intranasal delivery of exosomes loaded with a stat3 inhibitor reduced brain inflammation and slowed brain tumor growth. depiction of a dendrimer. a dendron represents a single unit of a dendrimer. dendrimers dendrimers are polymeric macromolecules with a branched network similar to a tree structure. generally, they are spherical and homogeneous. surface charge and molecule chemistry can play crucial role with drug interaction and release. poly(amidoamine) (pamam) dendrimers are the most commonly used system. a study investigated potential application of dendrimer-based formulation of haloperidol. intranasal administration showed improved targeting, and solubility as well as high concentrations in the brain. drugs can be loaded in dendrimers through formulation and nanoconstruct. importance of physiochemical properties for drug delivery systems to bypass the blood brain barrier, modifications of physiochemical properties can enhance safety and efficacy. size, surface charge, and lipophilicity play a major role in substance bypassing the blood brain barrier. smaller, positively charged, or more lipophilic molecules enhance efficacy of nose-to-brain delivery. decrease in delivery system size increases permeation. as the membrane is negatively charged, a particle with positive surface charge interacts electrostatically which enhances bioadhesion. carriers with more lipophilicity exert better mucoadhesion and residence time. drug system ph, solubility, and hydrogen bonding potential are other physiochemical properties which should be evaluated.