Nasal delivery offers many benefits over traditional approaches to vaccine administration. These include ease of administration without needles that reduces issues associated with needlestick injuries and disposal. Additionally, this route offers easy access to a key part of the immune system that can stimulate other mucosal sites throughout the body. Increased acceptance of nasal vaccine products in both adults and children has led to a burgeoning pipeline of nasal delivery technology. Key challenges and opportunities for the future will include translating in vivo data to clinical outcomes. Particular focus should be brought to designing delivery strategies that take into account the broad range of diseases, populations and healthcare delivery settings that stand to benefit from this unique mucosal route. In this review the current state of the art in nasal vaccine delivery will be described along with future prospects. A brief introduction to the anatomy and physiology of the nasal cavity will highlight the advantages and disadvantages of the route. Encapsulation and presentation methods along with particular formulation considerations for the nasal route will also be discussed.There are many mucosal routes which have been regarded as potential sites for vaccine delivery such as oral, nasal, pulmonary, conjunctival, rectal and vaginal mucosa. However, for practical and cultural reasons researchers have tended to focus only on oral, nasal, and pulmonary administration. 1 Needlefree vaccines offer many advantages over traditional vaccination approaches including convenience, cost, ease of administration and disposal.There are several needle free methods of vaccination such as transdermal delivery and mucosal delivery. 2,3 Mucosal immunization has been successfully used in human vaccination. The human mucosal immune system is large and specialized in performing inspection for foreign antigens to protect the surfaces themselves and of course human body interior. Since most infections affect or start from mucosal surfaces, using a mucosal route of vaccination is of great interest and provides a rational reason to induce a protective immune response. 3 Nasal delivery of vaccine offers an easily accessible route to the immune system.The nose has the function of olfactory detection (sense of smell) and also filtration, humidification and temperature control of air as it enters the respiratory system. Moving from front to back the areas of the nasal cavity are the nasal vestibule, the respiratory region, and the olfactory region. The nasal cavity is divided by the septum to form the left and right nares, which lead into the left and right choana before opening onto the nasopharynx at the top of the throat. The turbinates bound the nasal walls and are responsible for air conditioning and the large mucosal surface area of the nasal cavity. The nose is also the main port of entry for many pathogens. The first barrier to foreign bodies is hair at the entrance to the nares, the nostrils, which successfully keeps ou...
There is a pressing need for effective needle-free vaccines that are stable enough for use in the developing world and stockpiling. The inclusion of the cationic lipid DDA and the PEG-containing moiety TPGS into liposomes has the potential to improve mucosal delivery. The aim of this study was to develop stable lyophilized cationic liposomes based on these materials suitable for nasal antigen delivery. Liposomes containing DDA and TPGS were developed. Size and zeta potential measurements, ex vivo, CLSM cell penetration study and cell viability investigations were made. Preliminary immunisation and stability studies using ovalbumin were performed. The liposomes exhibited suitable size and charge for permeation across nasal mucosa. DDA and TPGS increased tissue permeation in ex vivo studies and cell uptake with good cell viability. The liposomes improved immune response both locally and vaginally when compared to i.m administration or control liposomes delivered nasally. Additionally, the lyophilized products demonstrated good stability in terms of Tg, size and antigen retention. This study has shown that the novel liposomes have potential for development as a mucosal vaccine delivery system. Furthermore, the stability of the lyophilized liposomes offers potential additional benefits in terms of thermal stability over liquid formats.
Introduction: Curcumin faces a major challenge in clinical use due to its poor aqueous solubility, which affects its bioavailability over oral use. The present study was carried out to overcome this problem. Methods: An amorphous micellar curcumin-spray dried powder (MC-SDP) with selfassembled casein was prepared by the addition of sucrose as a protectant. The dry powder of curcumin-loaded micelles was obtained by a spray-drying technique in the presence of sucrose as a protectant. The MC-SDP in the form of dry powder was further developed into tablets to investigate the dissolution profile. The physical properties of preformed powder were characterized by differential thermal analysis (DTA), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Quantitative analysis in the form of solutions was analyzed by high-performance liquid chromatography (HPLC). Results: The physical properties demonstrated that MC-SDP varies from dented to smoother surfaces as a function of sucrose. Furthermore, melting transitions of curcumin in the form of MC-SDP were broadened in all sample mixtures, as observed in the DTA thermogram. The XRD spectra showed that the sharp and very intense peaks of single curcumin crystalline structure no longer existed in all MC-SDP forms, indicating that the mixtures were amorphous. Moreover, a further dissolution study of MC-SDP showed a significant increase of drug dissolved with the presence of sucrose, where >80% of curcumin from MC-SDP was dissolved within 30 min. Conclusion: The study demonstrated the manufacture of micellar spray-dried powder that would contribute to the development of oral delivery of curcumin.
We report the formulation of novel composite nanoparticles that combine the high transfection efficiency of cationic peptide-DNA nanoparticles with the biocompatibility and prolonged delivery of polylactic acid–polyethylene glycol (PLA-PEG). The cationic cell-penetrating peptide RALA was used to condense DNA into nanoparticles that were encapsulated within a range of PLA-PEG copolymers. The composite nanoparticles produced exhibited excellent physicochemical properties including size <200 nm and encapsulation efficiency >80%. Images of the composite nanoparticles obtained with a new transmission electron microscopy staining method revealed the peptide-DNA nanoparticles within the PLA-PEG matrix. Varying the copolymers modulated the DNA release rate >6 weeks in vitro. The best formulation was selected and was able to transfect cells while maintaining viability. The effect of transferrin-appended composite nanoparticles was also studied. Thus, we have demonstrated the manufacture of composite nanoparticles for the controlled delivery of DNA.
The present study was to investigate the effect of cellulose matrix and oligosaccharide on solid state and morphology characteristics of freeze-dried cationic dimethyldioctadecylammonium (DDA)-based liposomes encapsulating ovalbumin (OVA). The OVA-containing liposomes were protected using cellulose derivative matrix and oligosaccharide. Despite the fact that saccharides are known to preserve protein and lipid membranes during drying, however, collapse structure are often addressed. In other side, cellulose matrix potentially prevents collapsing as it has been widely used for matrix in drug delivery formulations to increase the mass for compact matrices of resultant products. Their solid state characteristics were determined in terms of their crystallinity using X-Ray diffraction (XRD), thermal properties and detection of phase separation using differential scanning calorimetry (DSC). Furthermore, their morphology was observed using scanning electron microscopy and transmission electron microscopy. The study revealed that formulation with either oligosaccharide and cellulose matrix demonstrated a miscible mixture with DDA and soy phosphatidylcholine (SPC) that might construct stable dried liposomal formulation. Phase separation was not observed in formula with combination of oligosaccharide and cellulose matrix where their DSC thermograms showed glass transition indicating amorphous structure and miscible mixture. XRD confirmed the absence of crystal-like properties, demonstrating prevented crystallization. The dry products were porous with spherical liposomes trapped in the matrices, signifying the ease in reconstitution. Furthermore, OVA were well-preserved as its recovery was more than 80%. The preservation of both liposomes and protein antigen were found to be dependent upon the incorporation of both oligosaccharide and cellulose matrix included in the formulation.
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