Nanocarriers Targeting Dendritic Cells for Pulmonary Vaccine Delivery

Kunda, Nitesh K.; Somavarapu, Satyanarayana; Gordon, Stephen B.; Hutcheon, Gillian A.; Saleem, Imran

doi:10.1007/s11095-012-0891-5

Cited by 78 publications

(53 citation statements)

References 126 publications

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“…A dry powder vaccine delivered via the inhalation route can overcome certain challenges such as invasiveness, cold-chain requirements, low stability and integrity of the antigen that are often associated with the traditional liquid based vaccines currently available in the market (Al-fagih et al, 2011;Blank et al, 2011;Kunda et al, 2013). To address these issues in this study, a dry powder vaccine containing antigen adsorbed polymeric NPs for delivery via inhalation was successfully developed.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Kunda

Alfagih

Miyaji

et al. 2015

International Journal of Pharmaceutics

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Pneumonia, caused by Streptococcus pneumoniae, mainly affects the immune compromised, the very young and the old, and remains one of the leading causes of death.A steady rise in disease numbers from non-vaccine serotypes necessitates a new vaccine formulation that ideally has better antigen stability and integrity, does not require cold-chain and can be delivered non-invasively. In this study, a dry powder vaccine containing an important antigen of S. pneumoniae, pneumococcal surface protein A (PspA) that has shown cross-reactivity amongst serotypes to be delivered via the pulmonary route has been formulated. The formulation contains the antigen PspA adsorbed onto the surface of polymeric nanoparticles encapsulated in L-leucine microparticles that can be loaded into capsules and delivered via an inhaler. We have successfully synthesized particles of ~150 nm and achieved ~ 20 µg of PspA adsorption per mg of NPs. In addition, the spray-dried powders displayed a FPF of 74.31±1.32% and MMAD of 1.70±0.03 μm suggesting a broncho-alveolar lung deposition facilitating the uptake of the nanoparticles by dendritic cells. Also, the PspA released from the dry powders maintained antigen stability (SDS-PAGE), integrity (Circular dichroism) and activity (lactoferrin binding assay). Moreover, the released antigen also maintained its antigenicity as determined by ELISA.

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Section: Introductionmentioning

confidence: 99%

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Kunda

Alfagih

Miyaji

et al. 2015

International Journal of Pharmaceutics

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“…Furthermore, the respiratory tract represents an attractive target organ, given its enormous interface where interaction between DCs and novel inhalable nanocarrier-based vaccines may occur. 9,10 DCs are heterogeneous and exist as multiple distinct subsets. 11 Upon activation by antigen capture, cytokines, or lipopolysaccharides (LPS), immature DCs undergo a maturation process into so-called mature DCs.…”

Section: Introductionmentioning

confidence: 99%

Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation

Seydoux¹,

Rothen‐Rutishauser²,

Nita³

et al. 2014

IJN

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Introduction Nanosized particles may enable therapeutic modulation of immune responses by targeting dendritic cell (DC) networks in accessible organs such as the lung. To date, however, the effects of nanoparticles on DC function and downstream immune responses remain poorly understood. Methods Bone marrow–derived DCs (BMDCs) were exposed in vitro to 20 or 1,000 nm polystyrene (PS) particles. Particle uptake kinetics, cell surface marker expression, soluble protein antigen uptake and degradation, as well as in vitro CD4 + T-cell proliferation and cytokine production were analyzed by flow cytometry. In addition, co-localization of particles within the lysosomal compartment, lysosomal permeability, and endoplasmic reticulum stress were analyzed. Results The frequency of PS particle–positive CD11c + /CD11b + BMDCs reached an early plateau after 20 minutes and was significantly higher for 20 nm than for 1,000 nm PS particles at all time-points analyzed. PS particles did not alter cell viability or modify expression of the surface markers CD11b, CD11c, MHC class II, CD40, and CD86. Although particle exposure did not modulate antigen uptake, 20 nm PS particles decreased the capacity of BMDCs to degrade soluble antigen, without affecting their ability to induce antigen-specific CD4 + T-cell proliferation. Co-localization studies between PS particles and lysosomes using laser scanning confocal microscopy detected a significantly higher frequency of co-localized 20 nm particles as compared with their 1,000 nm counterparts. Neither size of PS particle caused lysosomal leakage, expression of endoplasmic reticulum stress gene markers, or changes in cytokines profiles. Conclusion These data indicate that although supposedly inert PS nanoparticles did not induce DC activation or alteration in CD4 + T-cell stimulating capacity, 20 nm (but not 1,000 nm) PS particles may reduce antigen degradation through interference in the lysosomal compartment. These findings emphasize the importance of performing in-depth analysis of DC function when developing novel approaches for immune modulation with nanoparticles.

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“…In humans, the primary bronchi divide into the left and right lung, and each lobe further divides into three lobes on the right side and two lobes on the left (Kunda et al, 2013). Each lung branches into at least 23 generations with the first 16 generations made up of bronchi and bronchioles, and by the 17 th generation alveoli begin to appear on the respiratory walls (Weibel, 1963).…”

Section: Pulmonary Delivery In Humans 21 Lung Anatomy and Physiologymentioning

confidence: 99%

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

Price

Kunda

Muttil

2019

KONA

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Significant progress has been made over the last half-century in delivering therapeutics by the pulmonary route. Inhaled therapeutics are administered to humans using metered-dose inhalers, nebulizers, or dry powder inhalers, and each device requires a different formulation strategy for the therapeutic to be successfully delivered into the lung. In recent years, there has been a shift to the use of dry powder inhalers due to advantages in the consistency of the dose delivered, ease of administration, and formulation stability. Numerous preclinical studies, involving small and large animals, have evaluated dry powder drugs, vaccines, and immunotherapeutics delivered by the pulmonary route. These studies used different dry powder delivery devices including nose-only, whole-body, and intratracheal administration systems, each of which works with different aerosolization mechanisms. Unfortunately, these delivery platforms usually lead to variable powder deposition in the respiratory tract of animals. In this review, we will discuss obstacles and variables that affect successful pulmonary delivery and uniform powder deposition in the respiratory tract, such as the type of delivery device, dry powder formulation, and the animal model used. We will conclude by outlining factors that enhance the reproducible deposition of dry powders in the respiratory tract of preclinical animal models and identifying knowledge and technology gaps within the field. We will also outline the important factors necessary for successful translation of studies performed in preclinical models to humans.

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Nanocarriers Targeting Dendritic Cells for Pulmonary Vaccine Delivery

Cited by 78 publications

References 126 publications

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Pulmonary dry powder vaccine of pneumococcal antigen loaded nanoparticles

Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation

Challenges Associated with the Pulmonary Delivery of Therapeutic Dry Powders for Preclinical Testing

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