Direct nose-to-brain delivery has been raised as a non-invasive powerful strategy to deliver drugs to the brain bypassing the blood-brain barrier (BBB). This study aimed at preparing and characterizing an innovative composite formulation, associating the liposome and hydrogel approaches, suitable for intranasal administration. Thermosensitive gel formulations were obtained based on a mixture of two hydrophilic polymers (Poloxamer 407, P407 and Poloxamer 188, P188) for a controlled delivery through nasal route via liposomes of an active pharmaceutical ingredient (API) of potential interest for Alzheimer’s disease. The osmolarity and the gelation temperature (T° sol-gel) of formulations, defined in a ternary diagram, were investigated by rheometry and visual determination. Regarding the issue of assays, a mixture composed of P407/P188 (15/1%, w/w) was selected for intranasal administration in terms of T° sol-gel and for the compatibility with the olfactory mucosal (280 ± 20 mOsmol, pH 6). Liposomes of API were prepared by the thin film hydration method. Mucoadhesion studies were performed by using mucin disc, and they showed the good natural mucoadhesive characteristics of in situ gel formulations, which increased when liposomes were added. The study demonstrated successful pharmacotechnical development of a promising API-loaded liposomes in a thermosensitive hydrogel intended for nasal Alzheimer’s disease treatment.

The aim of the present work was to encapsulate paclitaxel (Ptx) in various lipid nanocapsules (LNCs) formulations and then to compare their pharmacokinetics and efficacy on a subcutaneous isograft model in rats. Three different Ptx formulations were obtained. Drug payloads ranged from 1.32 to 3.62 mg Ptx/g of formulation. After oral administration the area under concentration-time curve was higher (p < 0.05) if Ptx was encapsulated, (1,2 Distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(PEG)] (DSPE-PEG-NH2)) LNCs displaying the highest area under concentration-time curve (p < 0.05). Efficacy was better than control for standard LNCs after oral administration (p < 0.05) and for (DSPE-PEG-NH2) LNCs after intravenous administration. Despite good absorption, (DSPE-PEG-NH2) LNCs failed to remain efficient after oral route. This study highlights the importance of efficacy studies paired to pharmacokinetic studies for nanomedicines.

Peer reviewed article authored by (Groo AC, Saulnier P, Gimel JC, Gravier J, Ailhas C, Benoit JP, Lagarce F). Read article or submit your manuscript for publishing.

Introduction: Resistance to traditional antibiotics is an increasingly serious problem. Antimicrobial peptides (AMPs) have emerged as a new therapeutic class with great potential against infectious diseases, as they are less prone to induce resistance. Nanotechnology-based delivery strategies can improve the efficiency and stability of AMPs, particularly against proteolytic degradation. Lipid nanocapsules (LNCs) are a new generation of biomimetic nanocarriers and were used in this study to deliver peptides. Methods: AMP-loaded reverse micelles (RM) were developed and incorpo­rated into LNCs by the phase inversion process and the antimicrobial activity of the AMPs-loaded LNC was evaluated by the minimum inhibitory concentration method. We studied the activity of AMP solutions and AMP-loaded LNCs against Gram-positive and Gram-negative bacterial strains and then evaluated the encapsulation of a new cationic AMP called AP138. Finally, we analyzed the effect of enzymatic attack on AP138 and AP138-RM-LNCs after incubation with trypsin. Results: AP138 was efficiently encapsulated in the LNCs (encapsulation efficiency = 97.8% at a drug loading of 0.151%), resulting in protection against degradation by proteases and the preservation of antimicrobial activity against Staphylococcus aureus, including methicillin-resistant Staphylococcus aureus. Conclusion: This study shows that RM-LNCs are an excellent candidate system to deliver AMPs.