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Development of solid dispersion lipid nanoparticles for improving skin delivery.

ABSTRACT: Applications of poorly water-soluble drugs in skin delivery pose several challenges to pharmaceutical formulation. This research originally developed solid lipid nanoparticles (SLNs) packaging a modified core of a solid dispersion (SD) in the lipid matrix to modulate the skin release patterns. Curcumin (CUR) was selected as the poorly water-soluble drug applied in the formulation. The designed system, so-called solid dispersion lipid nanoparticles (SD-SLNs), was fabricated by incorporating a solidifying SD or a non-solidifying SD into the core of the SLNs by ultrasonication. Release studies illustrated an important enhancement in the drug release of the proposed system compared to pure CUR and SLN formulations without the presence of SD as the modified core, which indicated the positive effect of the combined colloidal method of SD and SLNs. The physicochemical properties of the SD-SLN systems were also elucidated using powder X-ray diffraction, Fourier transform infrared spectroscopy, and particle size analysis. The drug was found to change to an amorphous state without any molecular interactions along with a marked particle size reduction. This work demonstrated the strong potential of applying a novel SD-SLN system for the skin delivery of a drug with poor water solubility.

SUBMITTER: Pham DTT

PROVIDER: S-EPMC6978615 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Development of solid dispersion lipid nanoparticles for improving skin delivery.

Pham Duong T T DTT Tran Phuong H L PHL Tran Thao T D TTD

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society 20190830 7

Applications of poorly water-soluble drugs in skin delivery pose several challenges to pharmaceutical formulation. This research originally developed solid lipid nanoparticles (SLNs) packaging a modified core of a solid dispersion (SD) in the lipid matrix to modulate the skin release patterns. Curcumin (CUR) was selected as the poorly water-soluble drug applied in the formulation. The designed system, so-called solid dispersion lipid nanoparticles (SD-SLNs), was fabricated by incorporating a sol ...[more]

PMID: 31997909

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Project description:In the golden age of pharmaceutical nanocarriers, we are witnessing a maturation stage of the original concepts and ideas. There is no doubt that nanoformulations are extremely valuable tools for drug delivery applications; the current challenge is how to optimize them to ensure that they are safe, effective and scalable, so that they can be manufactured at an industrial level and advance to clinical use. In this context, lipid nanoparticles have gained ground, since they are generally regarded as non-toxic, biocompatible and easy-to-produce formulations. Pharmaceutical applications of lipid nanocarriers are a burgeoning field for the transport and delivery of a diversity of therapeutic agents, from biotechnological products to small drug molecules. This review starts with a brief overview of the characteristics of solid lipid nanoparticles and discusses the relevancy of performing systematic preformulation studies. The main applications, as well as the advantages that this type of nanovehicles offers in certain therapeutic scenarios are discussed. Next, pharmacokinetic aspects are described, such as routes of administration, absorption after oral administration, distribution in the organism (including brain penetration) and elimination processes. Safety and toxicity issues are also addressed. Our work presents an original point of view, addressing the biopharmaceutical aspects of these nanovehicles by means of descriptive statistics of the state-of-the-art of solid lipid nanoparticles research. All the presented results, trends, graphs and discussions are based in a systematic (and reproducible) bibliographic search that considered only original papers in the subject, covering a 7 years range (2013-today), a period that accounts for more than 60% of the total number of publications in the topic in the main bibliographic databases and search engines. Focus was placed on the therapeutic fields of application, absorption and distribution processes and current efforts for the translation into the clinical practice of lipid-based nanoparticles. For this, the currently active clinical trials on lipid nanoparticles were reviewed, with a brief discussion on what achievements or milestones are still to be reached, as a way of understanding the reasons for the scarce number of solid lipid nanoparticles undergoing clinical trials.

Project description:Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease affecting the upper and lower motor neurons in the motor cortex and spinal cord. Abnormal accumulation of mutant superoxide dismutase I (SOD1) in motor neurons is a pathological hallmark of some forms of the disease. We have shown that the orderly progression of the disease may be explained by misfolded SOD1 cell-to-cell propagation, which is reliant upon its active endogenous synthesis. Reducing the levels of SOD1 is therefore a promising therapeutic approach. Antisense oligonucleotides (ASOs) can efficiently silence proteins with gain-of-function mutations. However, naked ASOs have a short circulation half-life and are unable to cross the blood brain barrier (BBB) warranting the use of a drug carrier for effective delivery. In this study, calcium phosphate lipid coated nanoparticles (CaP-lipid NPs) were developed for delivery of SOD1 ASO to motor neurons. The most promising nanoparticle formulation (Ca/P ratio of 100:1), had a uniform spherical core-shell morphology with an average size of 30 nm, and surface charge (?-potential) of -4.86 mV. The encapsulation efficiency of ASO was 48% and stability studies found the particle to be stable over a period of 20 days. In vitro experiments demonstrated that the negatively charged ASO-loaded CaP-lipid NPs could effectively deliver SOD1-targeted ASO into a mouse motor neuron-like cell line (NSC-34) through endocytosis and significantly down-regulated SOD1 expression in HEK293 cells. The CaP-lipid NPs exhibited a pH-dependant dissociation, suggesting that that the acidification of lysosomes is the likely mechanism responsible for facilitating intracellular ASO release. To demonstrate tissue specific delivery and localization of these NPs we performed in vivo microinjections into zebrafish. Successful delivery of these NPs was confirmed for the zebrafish brain, the blood stream, and the spinal cord. These results suggest that CaP-lipid NPs could be an effective and safe delivery system for the improved delivery of SOD1 ASOs to motor neurons. Further in vivo evaluation in transgenic mouse models of SOD1 ALS are therefore warranted.

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Development of solid dispersion lipid nanoparticles for improving skin delivery.

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Development of solid dispersion lipid nanoparticles for improving skin delivery.

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