The present study embarks upon the folic acid (FA) functionalization of chitosan nanoparticles and its implications on stability, oral bioavailability and hypoglycemic activity following oral administration.
There is a strong need for innovative and efficient drug delivery systems for ocular therapy development. However, testing intravitreal drug delivery systems without using live animals is challenging. Ex vivo animal models offer an interesting alternative. We analyzed the potential of using fresh porcine eyes obtained from the local slaughterhouse as a model for testing the intravitreal biodistribution and retention of liposomes with or without polyethylene glycol (PEG) conjugation and with different surface charges. The histology of the eyes was analyzed to localize the liposomes, and it was found that liposomes with PEG absorbed rapidly on the retina (within 1 h), with positively charged and PEG-coated liposomes being retained for at least 24 h. In parallel, fluorophotometry was employed on intact eyes, to determine the pharmacokinetics of the fluorophore calcein, as a substitute for a small hydrophilic therapeutic compound. We found a 4.5-fold increase in the vitreous half-life of calcein loaded in liposomes, compared with the free solution. Retinal toxicity was addressed using murine-derived retinal explant cultures. Liposomes were non-toxic up to 500 µg/mL. Toxicity was observed at 5 mg/mL for anionic and cationic liposomes, with 2-fold and 2.5-fold increased photoreceptor cell death, respectively. Overall, we could show that important ocular drug delivery considerations such as pharmacokinetics and biodistribution can be estimated in ex vivo porcine eyes, and may guide subsequent in vivo experiments.
Lipid nanocapsules
(LNCs) are increasingly being used for various
drug delivery applications due to their versatile nature and ability
to carry a wide variety of therapeutic drug molecules. In the present
investigation, small-angle X-ray (SAXS) and neutron scattering (SANS)
techniques were used to elucidate the structure of LNCs. Overall,
size measurements obtained from SAXS and SANS techniques were complemented
with dynamic light scattering, zeta potential, and cryogenic transmission
electron microscopy measurements. The structural aspects of LNCs can
be affected by drug loading and the properties of the drug. Here,
the impact of drug loading on the overall structure was evaluated
using DF003 as a model drug molecule. LNCs with varying compositions
were prepared using a phase inversion method. Combined analysis of
SAXS and SANS measurements indicated the presence of a core–shell
structure in the LNCs. Further, the drug loading did not alter the
overall core–shell structure of the LNCs. SANS data revealed
that the core size remained unchanged with a radius of 20.0 ±
0.9 nm for unloaded LNCs and 20.2 ± 0.6 nm for drug-loaded LNCs.
Furthermore, interestingly, the shell becomes thicker in an order
of ∼1 nm in presence of the drug compared to the shell thickness
of unloaded LNCs as demonstrated by SAXS data. This can be correlated
with the strong association of hydrophilic DF003 with Kolliphor HS
15, a polyethylene glycol-based surfactant that predominantly makes
up the shell, resulting in a drug-rich hydrated shell.
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