The use of liposomes as carriers for different types of drugs in formulations to be administered to the lungs brings a number of advantages, including the possibility of controlled release, prolongation of retention at the site of action or reduced systemic exposure. However, the main disadvantage of liposomal suspensions is their physical and chemical instability. Therefore, they are preferably converted to dry powders by several drying technologies. In doing so, it is necessary to include specific excipients in the formulation, in particular protectants (saccharides), protecting liposomes from changes during these processes.
- Keywords
- Colenter LD, Lipo C Askor Forte, LipoC Askor Junior,
- MeSH
- Colostrum chemistry cytology immunology MeSH
- Ascorbic Acid administration & dosage pharmacology metabolism MeSH
- Humans MeSH
- Liposomes administration & dosage pharmacology therapeutic use MeSH
- Microbiota physiology drug effects MeSH
- Drug Carriers MeSH
- Natural Childbirth MeSH
- Gastrointestinal Microbiome * genetics immunology drug effects MeSH
- Check Tag
- Humans MeSH
Rationale: The blood-brain barrier (BBB) is a major obstacle for drug delivery to the brain. Sonopermeation, which relies on the combination of ultrasound and microbubbles, has emerged as a powerful tool to permeate the BBB, enabling the extravasation of drugs and drug delivery systems (DDS) to and into the central nervous system (CNS). When aiming to improve the treatment of high medical need brain disorders, it is important to systematically study nanomedicine translocation across the sonopermeated BBB. To this end, we here employed multimodal and multiscale optical imaging to investigate the impact of DDS size on brain accumulation, extravasation and penetration upon sonopermeation. Methods: Two prototypic DDS, i.e. 10 nm-sized pHPMA polymers and 100 nm-sized PEGylated liposomes, were labeled with fluorophores and intravenously injected in healthy CD-1 nude mice. Upon sonopermeation, computed tomography-fluorescence molecular tomography, fluorescence reflectance imaging, fluorescence microscopy, confocal microscopy and stimulated emission depletion nanoscopy were used to study the effect of DDS size on their translocation across the BBB. Results: Sonopermeation treatment enabled safe and efficient opening of the BBB, which was confirmed by staining extravasated endogenous IgG. No micro-hemorrhages, edema and necrosis were detected in H&E stainings. Multimodal and multiscale optical imaging showed that sonopermeation promoted the accumulation of nanocarriers in mouse brains, and that 10 nm-sized polymeric DDS accumulated more strongly and penetrated deeper into the brain than 100 nm-sized liposomes. Conclusions: BBB opening via sonopermeation enables safe and efficient delivery of nanomedicine formulations to and into the brain. When looking at accumulation and penetration (and when neglecting issues such as drug loading capacity and therapeutic efficacy) smaller-sized DDS are found to be more suitable for drug delivery across the BBB than larger-sized DDS. These findings are valuable for better understanding and further developing nanomedicine-based strategies for the treatment of CNS disorders.
- MeSH
- Fluorescent Dyes administration & dosage MeSH
- Blood-Brain Barrier diagnostic imaging metabolism MeSH
- Drug Delivery Systems methods MeSH
- Liposomes administration & dosage MeSH
- Microbubbles MeSH
- Brain diagnostic imaging MeSH
- Mice, Nude MeSH
- Mice MeSH
- Nanomedicine methods MeSH
- Brain Diseases drug therapy MeSH
- Optical Imaging methods MeSH
- Ultrasonography methods MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- dynamika vysychání, FTIR,
- MeSH
- Antimicrobial Peptides MeSH
- Circular Dichroism methods utilization MeSH
- Dehydration MeSH
- Antimicrobial Cationic Peptides * MeSH
- Humans MeSH
- Liposomes administration & dosage MeSH
- Cell Membrane Permeability * physiology MeSH
- Prospective Studies MeSH
- Spectroscopy, Fourier Transform Infrared methods utilization MeSH
- Cell Membrane Structures classification MeSH
- Check Tag
- Humans MeSH
- Publication type
- Chart MeSH
- Keywords
- Tears again,
- MeSH
- Humans MeSH
- Liposomes administration & dosage pharmacology therapeutic use MeSH
- Ophthalmology methods MeSH
- Dry Eye Syndromes diagnosis etiology drug therapy MeSH
- Check Tag
- Humans MeSH
- MeSH
- Anthracyclines adverse effects therapeutic use MeSH
- Doxorubicin administration & dosage adverse effects therapeutic use MeSH
- Histological Techniques utilization MeSH
- Cardiomyopathies diagnosis etiology MeSH
- Cardiovascular System drug effects MeSH
- Humans MeSH
- Liposomes administration & dosage therapeutic use MeSH
- Breast Neoplasms drug therapy MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
- MeSH
- Adjuvants, Immunologic administration & dosage therapeutic use MeSH
- Albendazole administration & dosage therapeutic use MeSH
- Glucans administration & dosage therapeutic use MeSH
- Liposomes administration & dosage MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Toxocara canis parasitology MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Animals MeSH
