Dataset Information

Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs.

ABSTRACT: Nanohydrogels based on natural polymers, such as polysaccharides, are gaining interest as vehicles for therapeutic agents, as they can modify the pharmacokinetics and pharmacodynamics of the carried drugs. In this work, hyaluronan-riboflavin nanohydrogels were tested in vivo in healthy rats highlighting their lack of toxicity, even at high doses, and their different biodistribution with respect to that of native hyaluronan. They were also exploited as carriers of a hydrophobic model drug, the anti-inflammatory piroxicam, that was physically embedded within the nanohydrogels by an autoclave treatment. The nanoformulation was tested by intravenous administration showing an improvement of the pharmacokinetic parameters of the molecule. The obtained results indicate that hyaluronan-based self-assembled nanohydrogels are suitable systems for low-soluble drug administration, by increasing the dose as well as the circulation time of poorly available therapeutic agents.

SUBMITTER: Di Meo C

PROVIDER: S-EPMC6320896 | biostudies-other | 2018 Nov

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs.

Di Meo Chiara C Martínez-Martínez Mayte M Coviello Tommasina T Bermejo Marival M Merino Virginia V Gonzalez-Alvarez Isabel I Gonzalez-Alvarez Marta M Matricardi Pietro P

Pharmaceutics 20181103 4

Nanohydrogels based on natural polymers, such as polysaccharides, are gaining interest as vehicles for therapeutic agents, as they can modify the pharmacokinetics and pharmacodynamics of the carried drugs. In this work, hyaluronan-riboflavin nanohydrogels were tested in vivo in healthy rats highlighting their lack of toxicity, even at high doses, and their different biodistribution with respect to that of native hyaluronan. They were also exploited as carriers of a hydrophobic model drug, the an ...[more]

PMID: 30400294

Similar Datasets

Project description:The ability of small interfering RNA (siRNA) to efficiently silence the expression of specific genes provides the basis for exciting new therapies based on RNA interference (RNAi). The efficient intracellular delivery of siRNA from cell uptake through the endosomal trafficking pathways into the cytoplasm remains a significant challenge. Previously we described the synthesis of a new family of diblock copolymer siRNA carriers using controlled reversible addition-fragmentation chain transfer (RAFT) polymerization. The carriers were composed of a positively charged block of dimethylaminoethyl methacrylate (DMAEMA) to mediate siRNA binding and a second pH-responsive endosome releasing block composed of DMAEMA and propylacrylic acid (PAA) in roughly equimolar ratios and butyl methacylate (BMA). Here we describe the development of a new generation of siRNA delivery polymers based on this design that exhibit enhanced transfection efficiency and low cytotoxicity. This design incorporates a longer endosomolytic block with increased hydrophobic content to induce micelle formation. These polymers spontaneously form spherical micelles in the size range of 40 nm with CMC (critical micelle concentration) values of approximately 2 ?g/mL based on dynamic light scattering (DLS), (1)H NMR, electron microscopy, and selective partitioning of the small molecule pyrene into the hydrophobic micelle core. The siRNA binding to the cationic shell block did not perturb micelle stability or significantly increase particle size. The self-assembly of the diblock copolymers into particles was shown to provide a significant enhancement in mRNA knockdown at siRNA concentrations as low as 12.5 nM. Under these conditions, the micelle-based systems showed an 89% reduction in GAPDH mRNA levels as compared to only 23% (10 nM siRNA) for the nonmicelle system. The reduction in mRNA levels becomes nearly quantitative as the siRNA concentration is increased to 25 nM and higher. Flow cytometry analysis of fluorescent-labeled siRNA showed uptake in 90% of cells and a 3-fold increase in siRNA per cell compared to a standard lipid transfection agent. These results demonstrate the potential utility of this carrier design for siRNA drug delivery.

Project description:The current study aimed to develop poloxamer 407 (P407) gel for transungual delivery of antifungal hydrophobic drugs with sufficient gel strength and drug loading. Gel strength and drug loading of P407 gel was improved by use of functional additives. Hydration enhancement effect was used to select optimum nail penetration enhancer. Face-centered central composite design (FCCCD) was used to observe the effect of the selected penetration enhancer (thioglycolic acid (TGA)) and cosolvent (ethanol) on gelation behavior to develop formulation with enough loading of hydrophobic drug, i.e., terbinafine HCl (TBN), and its permeation across the nail plate without compromising on gel strength. It was observed that increasing concentration of P407 and TGA significantly reduced gelation temperature and enhanced the gel strength of P407 gel and can be used to improve P407 gel strength. Under the scanning electron microscope, the significant effect of TGA as an ungual penetration enhancer was observed on the morphology of the nail plate. Optimized P407 gel prepared with modified cold method showed a gelation temperature of 8.7 ± 0.16 °C, gel strength of 122 ± 7.5 s and drug loading of 1.2% w/w, which was four times more than the drug loading in the gels prepared with conventional cold method. Rheological behavior was pseudoplastic with 47.75 ± 3.48% of gel erosion after 12 washings and 67.21 ± 2.16% of drug release after 12 h. A cumulative amount of TBN permeated from P407 gel with and without PE after 24 h was 27.30 ± 4.18 and 16.69 ± 2.31 µg/cm2, respectively. Thioglycolic acid can be used as a nail penetration enhancer without the chemical modification or addition of extra additives while retaining the gel strength. Water miscible cosolvents with moderate evaporability such as ethanol, can be incorporated to P407 gel by minor modification in method of preparation to load the required dose of hydrophobic drugs. Developed P407 gel formulation with sufficient gel strength and drug loading will be a promising carrier for transungual delivery of hydrophobic antifungal agents.

Dataset Information

Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs.

Publications

Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure