Current Issue : January-March Volume : 2023 Issue Number : 1 Articles : 5 Articles
Peptide-based subunit vaccines include only minimal antigenic determinants, and, therefore, are less likely to induce allergic immune responses and adverse effects compared to traditional vaccines. However, peptides are weakly immunogenic and susceptible to enzymatic degradation when administered on their own. Hence, we designed polyelectrolyte complex (PEC)-based delivery systems to protect peptide antigens from degradation and improve immunogenicity. Lipopeptide (LCP-1) bearing J8 B-cell epitope derived from Group A Streptococcus (GAS) M-protein was selected as the model peptide antigen. In the pilot study, LCP-1 incorporated in alginate/cross-linked polyarginine-J8-based PEC induced high J8-specific IgG antibody titres. The PEC system was then further modified to improve its immune stimulating capability. Of the formulations tested, PEC-4, bearing LCP-1, alginate and cross-linked polylysine, induced the highest antibody titres in BALB/c mice following subcutaneous immunisation. The antibodies produced were more opsonic than those induced by mice immunised with other PECs, and as opsonic as those induced by antigen adjuvanted with powerful complete Freund’s adjuvant....
Pulmonary drug delivery aims to deliver particles deep into the lungs, bypassing the mouth–throat airway geometry. However, micron particles under high flow rates are susceptible to inertial impaction on anatomical sites that serve as a defense system to filter and prevent foreign particles from entering the lungs. The aim of this study was to understand particle aerodynamics and its possible deposition in the mouth–throat airway that inhibits pulmonary drug delivery. In this study, we present an analysis of the aerodynamics of inhaled particles inside a patient-specific mouth– throat model generated from MRI scans. Computational Fluid Dynamics with a Discrete Phase Model for tracking particles was used to characterize the airflow patterns for a constant inhalation flow rate of 30 L/min. Monodisperse particles with diameters of 7 μm to 26 μm were introduced to the domain within a 3 cm-diameter sphere in front of the oral cavity. The main outcomes of this study showed that the time taken for particle deposition to occur was 0.5 s; a narrow stream of particles (medially and superiorly) were transported by the flow field; larger particles > 20 μm deposited onto the oropharnyx, while smaller particles < 12 μm were more disperse throughout the oral cavity and navigated the curved geometry and laryngeal jet to escape through the tracheal outlet. It was concluded that at a flow rate of 30 L/min the particle diameters depositing on the larynx and trachea in this specific patient model are likely to be in the range of 7 μm to 16 μm. Particles larger than 16 μm primarily deposited on the oropharynx....
Lidocaine is a local anaesthetic drug with an amphiphilic structure able to self‐associate, under certain conditions, in molecular aggregates playing the role of both carrier and drug. The aim of this study was to determine the optimal conditions for obtaining vesicular carriers, called lidosomes. The new formulations were obtained using both lidocaine and lidocaine hydrochloride and different hydration medias (distilled water, acid, and basic aqueous solution). Lidosomes formulations were characterized in terms of size, ζ‐potential, drug retained, stability formulation, and ex vivo permeation profile. Moreover, lidosomes were incorporated in two different gel structures: one based on carboxymethylcellulose and one based on pluronic F‐127 to achieve suitable properties for a topical application. Results obtained showed that lidocaine showed a better performance to aggregate in vesicular carriers in respect to hydrochloride form. Consequently, only formulations comprised of lidocaine were studied in terms of skin permeation performance and as carriers of another model drug, capsaicin, for a potential combined therapy. Lidocaine, when in form of vesicular aggregates, acted as percutaneous permeation enhancer showing better permeation profiles with respect to drug solutions. Moreover, lidosomes created a significant drug depot into the skin from which the drug was available for a prolonged time, a suitable feature for a successful local therapy....
Ionic liquids (ILs) have been proven to be an efficient technology for enhancing drug skin permeability. However, the question of whether the two components of ILs are released synchronously in transdermal preparations has remained unclear. Thus, this study aimed to investigate the release characteristics of two components of ILs and their underlying molecular mechanism. The ILs containing flurbiprofen (FLU) and lidocaine (LID) were synthesized and characterized. The four typical acrylates pressure sensitive adhesives (PSAs) with different functional groups were synthesized and characterized. The effects of PSAs on the release characteristics of two components of ILs were investigated by drug release tests and verified by skin permeation experiments. The action mechanisms were revealed by FTIR, Raman, dielectric spectrum, and molecular docking. The results showed that the average release amount of FLU (0.29 μmol/cm2) and LID (0.11 μmol/cm2) of ILs in the four PSAs was significantly different (p < 0.05), which illustrated that the two components did not release synchronously. The PSA−none and PSA−OH with low permittivity (7.37, 9.82) interacted with drugs mainly by dipole-dipole interactions and hydrogen bonds. The PSA−COOH and PSA−CONH2 with high permittivity (11.19, 15.32) interacted with drugs mainly by ionic bonds and ionic hydrogen bonds. Thus, this study provides scientific guidance for the application of ILs in transdermal preparations....
Quercetin (QCT), a natural flavonoid, is of research interest owing to its pharmacological properties. However, its pharmacokinetic limitations could hinder its widespread therapeutic use. Nanocarriers, especially solid lipid nanoparticles (SLNs), might overcome this constraint. This study aimed to investigate QCT-loaded SLNs prepared via a new approach using a volatile oil. The phase-inversion temperature method was used to incorporate rosemary oil (RMO) into SLNs prepared using solid lipids possessing different chemical structures. Among the solid lipids used in the formulations, trilaurin (TLR) exhibited the smallest particle size and good stability after a temperature cycling test. SLNs prepared with a ratio of RMO to TLR of 1:3 could load QCT with an entrapment efficiency of >60% and drug loading of ~2% w/w. The smallest particle size was achieved using the polyoxyethylene-hydrogenated castor oil RH40, and the particle size depended on the concentration. The drug-release profile of QCT_TLR exhibited prolonged biphasic release for >24 h. QCT_TLR was a safe formulation, as indicated by a cell viability percentage of >75% at <2% v/v. In a computer simulation, the system with RMO enabled smaller sized SLNs than those without RMO. This new discovery shows great promise for producing SLNs via the phase-inversion temperature method with incorporation of volatile oil, particularly for delivering compounds with limited water solubility....
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