Nasal Vaccine Delivery Research Articles

A Review on Intranasal Drug Delivery System with Recent Advancement

The aim of the present research is to explain the recent advancement of nasal drug delivery system. Intranasal Therapy has been an accepted form of treatment in the Ayurvedic system of Indian Medicine. The attention in intranasal delivery of drugs as a non-invasive is increased. We have also discussed advantages, disadvantages, mechanism of action and application of nasal drug delivery system in local delivery, systematic delivery, and Nasal vaccine and CNS delivery of the drug. We are discussed here relevant aspects of biological, physicochemical and pharmaceutical factors of nasal cavity that must be considered during the process of innovation and advance of new drugs for nasal delivery as well as in their incorporation into appropriate nasal Pharmaceutical formulations. Nasal route is more suitable for those drugs which cannot be administered orally due to gastric degradation or hepatic first pass metabolism of the drug. Intranasal drug delivery is found much promising route for administration of peptides and protein drugs. Much has been investigated and much more are to be investigated for the recent development of nasal drug delivery system.

Potential of Translationally Controlled Tumor Protein-Derived Protein Transduction Domains as Antigen Carriers for Nasal Vaccine Delivery.

Nasal vaccination offers a promising alternative to intramuscular (i.m.) vaccination because it can induce both mucosal and systemic immunity. However, its major drawback is poor absorption of large antigens in the nasal epithelium. Protein transduction domains (PTDs), also called cell-penetrating peptides, have been proposed as vehicles for nasal delivery of therapeutic peptides and proteins. Here, we evaluated the potential of a mutant PTD derived from translationally controlled tumor protein (designated TCTP-PTD 13) as an antigen carrier for nasal vaccines. We first compared the l- and d-forms of TCTP-PTD 13 isomers (l- or d-TCTP-PTD 13) as antigen carriers. Studies in mice demonstrated that nasally administered mixtures of the model antigen ovalbumin (OVA) and d-TCTP-PTD 13 induced higher plasma IgG titers and secretory IgA levels in nasal washes than nasally administered OVA alone, OVA/l-TCTP-PTD 13, or i.m.-injected OVA. Plasma IgG subclass responses (IgG1 and IgG2a) of mice nasally administered OVA/d-TCTP-PTD 13 showed that the predominant IgG subclass was IgG1, indicating a Th2-biased immune response. We also used synthetic CpG oligonucleotides (CpG) as a Th1 immune response-inducing adjuvant. Nasally administered CpG plus OVA/d-TCTP-PTD 13 was superior in eliciting systemic and mucosal immune responses compared to those induced by nasally administered OVA/d-TCTP-PTD 13. Furthermore, the OVA/CpG/d-TCTP-PTD 13 combination skewed IgG1 and IgG2a profiles of humoral immune responses toward a Th1 profile. These findings suggest that TCTP-derived PTD is a suitable vehicle to efficiently carry antigens and to induce more powerful antigen-specific immune responses and a more balanced Th1/Th2 response when combined with a DNA adjuvant.

Nasal immunization with mannan-decorated mucoadhesive HPMCP microspheres containing ApxIIA toxin induces protective immunity against challenge infection with Actinobacillus pleuropneumoiae in mice

The development of subunit mucosal vaccines requires an appropriate delivery system or an immune modulator such as an adjuvant to improve antigen immunogenicity. The nasal route for vaccine delivery by microparticles has attracted considerable interest, although challenges such as the rapid mucociliary clearance in the respiratory mucosa and the low immunogenicity of subunit vaccine still remain. Here, we aimed to develop mannan-decorated mucoadhesive thiolated hydroxypropylmethyl cellulose phthalate (HPMCP) microspheres (Man-THM) that contain ApxIIA subunit vaccine – an exotoxin fragment as a candidate for a subunit nasal vaccine against Actinobacillus pleuropneumoniae. For adjuvant activity, mucoadhesive thiolated HPMCP microspheres decorated with mannan could be targeted to the PRRs (pathogen recognition receptors) and mannose receptors (MR) of antigen presenting cells (APCs) in the respiratory immune system. The potential adjuvant ability of Man-THM for intranasal immunization was confirmed by in vitro and in vivo experiments. In a mechanistic study using APCs in vitro, it was found that Man-THM enhanced receptor-mediated endocytosis by stimulating the MR of APCs. In vivo, the nasal vaccination of ApxIIA-loaded Man-THM in mice resulted in higher levels of mucosal sIgA and serum IgG than mice in the ApxIIA and ApxIIA-loaded THM groups due to the specific recognition of the mannan in the Man-THM by the MRs of the APCs. Moreover, ApxIIA-containing Man-THM protected immunized mice when challenged with strains of A. pleuropneumoniae serotype 5. These results suggest that mucoadhesive Man-THM may be a promising candidate for a nasal vaccine delivery system to elicit systemic and mucosal immunity that can protect from pathogenic bacteria infection.

Carrier-based dry powder formulation for nasal delivery of vaccines utilizing BSA as model drug

Dry powder formulations for nasal vaccine delivery offer versatile advantages compared to liquid formulations, such as increased storage stability and simplified administration. The objective of the present study was the development of a dry powder nasal vaccine formulation making use of antigen-loaded chitosan microparticles. Special emphasis was put on the development and characterization of a formulation which can realistically be used in humans by means of a nasal dry powder sprayer. Microparticles of chitosan with bovine serum albumin as model antigen were produced by spray drying and showed a particle size of about 3μm. In order to improve nasal deposition and dispersibility, powder blends with low separation tendency were prepared. A range of sugar alcohols (mannitol, sorbitol, maltitol) was evaluated as carriers. Among the tested carriers, blends with spray-granulated mannitol showed the most adequate deposition profile without simulated nasal inspiration and were very well dispersible by a nasal dry powder device. In conclusion, this study illustrates a simple and effective strategy for the development of a dry powder vaccine formulation for nasal administration.

Mannan-decorated thiolated Eudragit microspheres for targeting antigen presenting cells via nasal vaccination

Mucosal vaccination of protein as an antigen requires appropriate delivery or adjuvant systems to deliver antigen to mucosal immune cells efficiently and generate valid immune responses. For successful nasal immunization, the obstacles imposed by the normal process of mucociliary clearance which limits residence time of applied antigens and low antigen delivery to antigen presenting cells (APCs) in nasal associated lymphoid tissue (NALT) need to be overcome for the efficient vaccination. Here, we prepared mucoadhesive and mannan-decorated thiolated Eudragit microspheres (Man-TEM) as a nasal vaccine carrier to overcome the limitations. Mucoadhesive thiolated Eudragit (TE) were decorated with mannan for targeting mannose receptors (MR) in antigen presenting cells (APCs) to obtain efficient immune responses. The potential adjuvant ability of Man-TEM for intranasal immunization was confirmed by in vitro and in vivo experiments. In mechanistic study using APCs in vitro, we obtained that Man-TEM enhanced the receptor-mediated endocytosis by stimulating the MR receptors of APCs. The nasal vaccination of OVA-loaded Man-TEM in mice showed higher levels of serum IgG and mucosal sIgA than the soluble OVA group due to the specific recognition of MR of APCs by the mannan in the Man-TEM. These results suggest that mucoadhesive and Man-TEM may be a promising candidate for nasal vaccine delivery system to elicit systemic and mucosal immunity.

Development of chitosan–pullulan composite nanoparticles for nasal delivery of vaccines: in vivo studies

Here, we aimed at developing chitosan/pullulan composite nanoparticles and testing their potential as novel systems for the nasal delivery of diphtheria toxoid (DT). All the chitosan derivatives [N-trimethyl (TMC), chloride and glutamate] and carboxymethyl pullulan (CMP) were synthesised and antigen-loaded composites were prepared by polyion complexation of chitosan and pullulan derivatives (particle size: 239–405 nm; surface charge: +18 and +27 mV). Their immunological effects after intranasal administration to mice were compared to intramuscular route. Composite nanoparticles induced higher levels of IgG responses than particles formed with chitosan derivative and antigen. Nasally administered TMC–pullulan composites showed higher DT serum IgG titre when compared with the other composites. Co-encapsulation of CpG ODN within TMC-CMP-DT nanoparticles resulted in a balanced Th1/Th2 response. TMC/pullulan composite nanoparticles also induced highest cytokine levels compared to those of chitosan salts. These findings demonstrated that TMC-CMP-DT composite nanoparticles are promising delivery system for nasal vaccination.

Development of chitosan–pullulan composite nanoparticles for nasal delivery of vaccines: optimisation and cellular studies

Nasal immunisation with nanoparticles has already shown promising results. In this study, nanoparticle composites carrying BSA for nasal vaccination prepared using electrostatic interaction process between polycation N-trimethyl chitosan chloride (TMC), chitosan glutamate (CG), chitosan chloride (CCl) and polyanion carboxymethyl pullulan (CMP). A mass ratio of 2:1 for TMC-CMP combination produced stable nanocarriers. For CCl-CMP and CG-CMP formulations needed a mass ratio of 3:1. Loading efficiency was >90% for all formulations. Nanoparticles’ size ranged from 207 to 603 nm. The surface charge of the complexes varied between +14 and +33 mV. SDS-PAGE integrity of the model antigen was also demonstrated. MTT studies showed that nanoparticle composites were less toxic to Calu-3 cells than the particles of cationic polymers alone. FITC-BSA loaded nanoparticles efficiently taken up by J774A.1 macrophages as confirmed by confocal microscopy highlighting the potential of these novel nanoparticulate carriers’ use for nasal vaccination.

Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.

We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [18F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [18F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans.

Evaluation of dual nasal delivery of infectious hematopoietic necrosis virus and enteric red mouth vaccines in rainbow trout (Oncorhynchus mykiss)

Farmed fish are susceptible to different infectious disease agents including viruses and bacteria. Thus, multivalent vaccines or vaccination programs against two or more pathogens are valuable tools in aquaculture. Recently, nasal vaccines have been shown to be very effective in rainbow trout. The current study investigates, for the first time, the use of the nasal route in dual vaccination trials against two important aquatic diseases, infectious hematopoietic necrosis virus (IHN) and enteric red mouth (ERM) disease. Rainbow trout received live attenuated IHN virus (IHNV) vaccine and the ERM bacterin using four different vaccine delivery methods and were challenged with virulent IHNV or Yersinia ruckeri 7 (100deg day) and 28 (400deg day) days post-vaccination. The highest survival rates against IHNV at day 7 were obtained by nasal vaccination either when IHNV and ERM were delivered separately into each nare or when they were premixed and delivered to both nasal rosettes (group D). Protection at 28 days against IHNV was similar in all four vaccinated groups. Early protection against ERM was highest in fish that received each vaccine in separate nares (group B), whereas protection at 28 days was highest in the i.p. vaccinated group (group E), followed by the nasally vaccinated group (group B). Survival results were supported by histological observations of the left and right olfactory organ which showed strong immune responses one day (14deg days) after vaccination in group B vaccinated fish. These data indicate that dual vaccination against two different pathogens via the nasal route is a very effective vaccination strategy for use in aquaculture, particularly when each nare is used separately during delivery. Further long-term studies should evaluate the contribution of adaptive immunity to the protection levels observed.

The effect of cilia and the mucociliary clearance on successful drug delivery.

Nasal mucociliary clearance is one of the most important factors affecting nasal delivery of drugs and vaccines. This is also the most important physiological defense mechanism inside the nasal cavity. It removes inhaled (and delivered) particles, microbes and substances trapped in the mucus. Almost all inhaled particles are trapped in the mucus carpet and transported with a rate of 8-10 mm/h toward the pharynx. This transport is conducted by the ciliated cells, which contain about 100-250 motile cellular appendages called cilia, 0.3 µm wide and 5 µm in length that beat about 1000 times every minute or 12-15 Hz. For efficient mucociliary clearance, the interaction between the cilia and the nasal mucus needs to be well structured, where the mucus layer is a tri-layer: an upper gel layer that floats on the lower, more aqueous solution, called the periciliary liquid layer and a third layer of surfactants between these two main layers. Pharmacokinetic calculations of the mucociliary clearance show that this mechanism may account for a substantial difference in bioavailability following nasal delivery. If the formulation irritates the nasal mucosa, this mechanism will cause the irritant to be rapidly diluted, followed by increased clearance, and swallowed. The result is a much shorter duration inside the nasal cavity and therefore less nasal bioavailability.

Novel Intranasal Vaccine Delivery System by Chitosan Nanofibrous Membrane Containing N-Terminal Region of Ipad Antigen as a Nasal Shigellosis Vaccine, Studies in Guinea Pigs

Nasal Shigellosis vaccine is quite attractive for inducing a protective immune response. The reason is the invading effect of Shigella spp. to body through mucosal surfaces. Chitosan is a mucoadhesive polysaccharide with great potential for nasal vaccine delivery regarding to the exclusive features including biocompatibility, biodegradability, high charge density and non-toxicity. In this study, the potential of chitosan nano-fibrous membrane as a novel carrier system for the nasal delivery of shigella subunit vaccine was investigated. The antigen-containing chitosan nanofibrous membrane was prepared by electrospinning of chitosan/AcOH solution. Guinea pigs were vaccinated by direct administration of antigen-containing chitosan nanofibers into the nasal cavity. The guinea pigs immunized intranasal administered N-IpaD/NFs showed higher serum and mucosal antibody responses comparing to those of other groups. All immunized animals were subsequently protected against a challenge with wild-type S. flexneri 2a in a keratoconjunctivitis Sereny test that N-IpaD/NFs group was protective.

Development and characterization of surface modified PLGA nanoparticles for nasal vaccine delivery: Effect of mucoadhesive coating on antigen uptake and immune adjuvant activity

In this study, the efficacy of mucoadhesive polymers, i.e., chitosan and glycol chitosan as a mucoadhesive coating material in nasal vaccine delivery was investigated. The Hepatitis B surface Antigen (HBsAg) encapsulated PLGA, chitosan coated PLGA (C-PLGA), and Glycol chitosan coated PLGA (GC-PLGA) nanoparticles (NPs) were prepared. The formulations were characterized for particle size, shape, surface charge, and entrapment efficiency. The mucoadhesive ability of coated and non-coated NPs was determined using in vitro mucoadhesion and nasal clearance test. In addition, the systemic uptake and bio-distribution were also evaluated to understand the fate of NPs following nasal delivery. The immuno-adjuvant ability of various formulations was compared by measuring specific antibody titer in serum and secretory. The results indicated that PLGA NPs exhibit negative surface charge, whereas C-PLGA and GC-PLGA NPs exhibited positive surface charge. The GC-PLGA NPs demonstrated lower clearance and better local and systemic uptake compared to chitosan coated and uncoated PLGA NPs. In vivo immunogenicity studies indicated that GC-PLGA NPs could induce significantly higher systemic and mucosal immune response compared to PLGA and C-PLGA NPs. In conclusion, GC-PLGA NPs could be a promising carrier adjuvant for the nasal vaccine delivery for inducing a potent immune response at mucosal surface(s) and systemic circulation.

Foot and Mouth Disease virus-loaded fungal chitosan nanoparticles for intranasal administration: impact of formulation on physicochemical and immunological characteristics

Nasal vaccination is a promising, needle-free alternative route for parenteral vaccination. This study introduces a simple, scalable nasal vaccine delivery formulation for Foot and Mouth Disease virus (FMDv) using chitosan (CS) nanoparticles and assesses the potential of fungal CS for use as nanocarriers for mucosal vaccines. Fungal CS was extracted from fungal biomass and physiochemically characterized. FMDv-loaded CS nanoparticles, prepared using an ionic gelation technique, were characterized for particle size, zeta potential, morphology, loading efficiency and virus particle release. The immunogenicities of nasally applied FMDv-loaded fungal or commercial shrimp CS were compared with intraperitoneally administered fluid vaccine in guinea pigs. The nanoparticles had varied sizes (221.9–281.2 nm), positive electrical charge (+7 to +13 mV) and excellent antigen-loading capacity (93–97%). In vitro release studies revealed a biphasic virus particle release for all CS nanoparticles. Higher serum titers were developed with CS formulations than with free virus and were comparable with the titers for intraperitoneally administered fluid vaccine. Significantly higher IgA levels were found after the administration of nasal vaccine than after fluid vaccine or free virus. Overall, CS-FMDv nanoparticles stimulated humoral and mucosal immunity following intranasal administration. Fungal CS polymers were potent mucosal immunoadjuvants and showed promise as alternative sources of CS for mucosal vaccine formulations.

Anatomical and Histological Factors Affecting Intranasal Drug and Vaccine Delivery

The aim of this review is to provide an understanding of the anatomical and histological structure of the nasal cavity, which is important for nasal drug and vaccine delivery as well as the development of new devices. The surface area of the nasal cavity is about 160 cm2, or 96 m2 if the microvilli are included. The olfactory region, however, is only about 5 cm2 (0.3 m2 including the microvilli). There are 6 arterial branches that serve the nasal cavity, making this region a very attractive route for drug administration. The blood flow into the nasal region is slightly more than reabsorbed back into the nasal veins, but the excess will drain into the lymph vessels, making this region a very attractive route for vaccine delivery. Many of the side effects seen following intranasal administration are caused by some of the 6 nerves that serve the nasal cavity. The 5th cranial nerve (trigeminus nerve) is responsible for sensing pain and irritation following nasal administration but the 7th cranial nerve (facial nerve) will respond to such irritation by stimulating glands and cause facial expressions in the subject. The first cranial nerve (olfactory nerve), however, is the target when direct absorption into the brain is the goal, since this is the only site in our body where the central nervous system is directly expressed on the mucosal surface. The nasal mucosa contains 7 cell types and 4 types of glands. Four types of cells and 2 types of glands are located in the respiratory region but 6 cell types and 2 types of glands are found in the olfactory region.

Research Spotlight: Thermal-sensitive Hydrogels As Nasal Vaccine Delivery Systems

The National Key Laboratory of Biochemical Engineering established in 1995 is affiliated with the Institute of Process Engineering, Chinese Academy of Sciences (CAS), and located in Zhong-guan-cun (Beijing, China). The National Key Laboratory of Biochemical Engineering is working towards developments in the fields of bio-reaction, bioseparation and bio-formulation, by chemical and material methods. Over the last 5 years, approximately 200 scientists and students have worked at the laboratory, and published over 400 articles. Numerous universities, companies and institutes have established cooperative relationships with this laboratory, and over 70 cooperative research programs with other researchers have been conducted in the past few years.

Preliminary studies on the development of IgA-loaded chitosan–dextran sulphate nanoparticles as a potential nasal delivery system for protein antigens

This study describes the development of a biodegradable nanoparticulate system for the intranasal delivery of multiple proteins. Chitosan (CS)–dextran sulphate (DS) nanoparticles were developed and optimised for the incorporation of pertussis toxin (PTX) and a potential targeting ligand (immunoglobulin-A, IgA). In vitro characterization and in vivo uptake studies were performed for the evaluation of developed nanoparticles. The ratio of CS to DS, the order of mixing and pH of nanoparticle suspension were identified as important formulation factors governing the size and zeta potential of nanoparticles. An optimised CS–DS nanoparticle formulation prepared with the CS to DS weight ratio of 3 : 1 was used to load PTX and/or IgA. Entrapment efficiency of >90% was obtained for both. The in vivo uptake of IgA-loaded CS–DS nanoparticles in mice showed a preferential uptake of nanoparticles probably by nasal membranous or microfold cells following intranasal administration. The results of this study indicate the potential application of IgA-loaded CS–DS nanoparticles as a nasal vaccine delivery system.

Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review

Chitosan, a natural biodegradable polymer, is of great interest in biomedical research due to its excellent properties including bioavailability, nontoxicity, high charge density, and mucoadhesivity, which creates immense potential for various pharmaceutical applications. It has gelling properties when it interacts with counterions such as sulfates or polyphosphates and when it crosslinks with glutaraldehyde. This characteristic facilitates its usefulness in the coating or entrapment of biochemicals, drugs, antigenic molecules as a vaccine candidate, and microorganisms. Therefore, chitosan together with the advance of nanotechnology can be effectively applied as a carrier system for vaccine delivery. In fact, chitosan microspheres have been studied as a promising carrier system for mucosal vaccination, especially via the oral and nasal route to induce enhanced immune responses. Moreover, the thiolated form of chitosan is of considerable interest due to its improved mucoadhesivity, permeability, stability, and controlled/extended release profile. This review describes the various methods used to design and synthesize chitosan microspheres and recent updates on their potential applications for oral and nasal delivery of vaccines. The potential use of thiolated chitosan microspheres as next-generation mucosal vaccine carriers is also discussed.

Pharmaceutical and immunological evaluation of mucoadhesive nanoparticles based delivery system(s) administered intranasally

Tri-methyl chitosan synthesis accompanies polymer chain scission, which may affect the carrier and adjuvant properties of the polymer. The main objective of this study was to synthesize the tri-methylated chitosan using mild (TMC-M) and conventional (TMC) method and compare their efficacy as nasal vaccine delivery vehicle. During in vitro studies TMC-M nanoparticles showed the lowest nasal clearance rate when compared with chitosan (CS) and TMC nanoparticles. The immunogenicity of nanoparticles based delivery system(s) was assessed by measuring anti-HBsAg antibody titer in mice serum and secretions after intranasal administration. The alum based HBsAg vaccine injected subcutaneously was used as positive control. Results indicated that alum based HBsAg induced strong humoral but negligible mucosal immunity. However, TMC-M nanoparticles induced stronger immune response at both of the fronts as compared to generated by CS or TMC nanoparticles. Present study demonstrates that TMC-M can be a better carrier adjuvant for nasal subunit vaccines.

Mucosal vaccination: Lung versus nose

The induction of potent mucosal immune responses able to prevent the establishment of infection at the onset of mucosal pathogen colonisation represents a desirable but challenging goal for vaccine development. Here we compare nasal vaccine delivery with intra-pulmonary vaccination using a sheep lymphatic cannulation model. Our results demonstrate that nasal delivery of a non-infective ISCOMATRIX® influenza vaccine does not induce primary immune responses in the lymph draining the nasal lymph nodes, suggesting that local immune responses in the lymph nodes draining the nasal cavity are relatively weak. However, this mode of delivery can boost existing immunity in the nasal lymph. Using the same adjuvant we were able to induce very potent immune responses in both blood and bronchoalveolar lavage (BAL), following intra-pulmonary delivery of ISCOMATRIX® influenza vaccine, even when very small doses of antigen were employed. Lung delivery could also induce comparable immune responses against other recombinant antigens mixed with ISCOMATRIX® adjuvant and could therefore become a method of choice for the induction of immunity to mucosal pathogens infecting the lower respiratory tract.

Nanocarrier Aided Nasal Vaccination: An Experimental and Computational Approach

In the present study, an experimental and theoretical investigation on the nasal vaccine delivery is reported. Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) containing a model antigen, i.e., ovalbumin (OVA), and an adjuvant, i.e., monophosphoryl lipid A (MPLA), were prepared for nasal vaccine delivery. The nanoparticles, prepared by the double emulsion method, had an average particle size in the range of 296−401 nm and a zeta potential value of −14.3 to −23.2 mV. Depending on the initial OVA and MPLA concentrations in the recipe, the corresponding loadings varied from 1.07 to 10.16 wt % and from 0.177 to 1.081 wt %, respectively. The PLGA nanoparticles were found to be stable during their storage in a 9 wt % sucrose solution at 4 °C for 4 weeks. Examination of the OVA release profile from the PLGA nanoparticles in a physiological buffer solution (PBS) at 37 °C revealed an initial fast release of OVA located in the nanoparticles external surface area, followed by a lag phase of minimum release and a subsequent continuous release profile. The delivery and deposition of carrier droplets, containing PLGA nanoparticles, to the nasal cavity was determined using computational fluid dynamics (CFD) for steady-state inspiration and inlet velocities (vin) in the range of 1−20 m/s. Deposition efficiencies and spatial deposition distributions were found to be strongly dependent on the droplet size and volumetric flow rate. A nanoparticle release model was developed to determine the amount of nanoparticles delivered from the deposited carrier droplets to the nasal cavity surface by taking into account the droplet formation size and the residence time of deposited droplets in the nasal cavity. It was found that the average droplet size increased when the viscosity of the liquid droplet increased or the surface tension decreased, leading to longer residence times and, thus, to higher nanoparticle release rates from the deposited droplets.