Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral, biochemical, neurochemical and histological alterations in mice

Abstract

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3 full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50 mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNP) (equivalent to 25 mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNP, with mean particle size 237 nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNP at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.

Magnetite Nanoparticles Coated with PEG 3350-Tween 80: In Vitro Characterization Using Primary Cell Cultures

“…Tween 80 is a biocompatible non-ionic surfactant that binds with the plasma lipoprotein Apo-E, which attaches to Low-Density Lipoprotein (LDL) receptors on the brain micro vascular endothelial cells. This propriety can be used by the nanoparticles in order to delivery substances such as drugs into the brain [15,16]. Tween 80 has also been proposed for the delivery of drugs into cancerous cells [17], has been used as a coating for metallic nanoparticles [18,19], and is widely used in cosmetics, food and pharmaceutics.…”

New Approach in Ulcer Prevention and Wound Healing Treatment using Doxycycline and Amoxicillin/LDH Nanocomposites

“…Interestingly, Fig. 1C,D shows the presence of important bands of AMOX and DOXY in the spectra of Mg-Al LDH/AMOX and Mg-Al LDH/DOXY composites, indicating the successful loading of drugs in the Mg-Al LDH host 24,25 . In addition, the intensity of the NO 3 peak at 1381 cm −1 decreased, indicating the exchange of nitrate anions by the antibiotics 24 .…”

“…1C,D shows the presence of important bands of AMOX and DOXY in the spectra of Mg-Al LDH/AMOX and Mg-Al LDH/DOXY composites, indicating the successful loading of drugs in the Mg-Al LDH host 24,25 . In addition, the intensity of the NO 3 peak at 1381 cm −1 decreased, indicating the exchange of nitrate anions by the antibiotics 24 . In addition, some peaks shifted to new values; for example, the NO 3 group peak at 1381 cm −1 shifted to 1375 cm −1 , while some peaks, such as the peak related to the carbonyl group C=O stretching vibration of COO − in AMOX at 1775 cm −1 , disappeared for the Mg-Al LDH/AMOX nanocomposite, confirming the loading process.…”

Leveraging the interplay of nanotechnology and neuroscience: Designing new avenues for treating central nervous system disorders

“…NP-mediated drug delivery for the enhancement of brain uptake has been studied as a means to increase bioavailability and lower dosage to potentially decrease drug side effects [131,132]. Intranasal administration of anti-depressants or anti-psychotics using alginate NPs, thiolated-chitosan NPs, and PGLA-chitosan NPs have shown greater efficacy in preclinical models as compared to oral administration due to direct uptake to the brain, and bypassing the BBB and first pass metabolism [133][134][135][136][137]. A critical next step, however, is to validate improved efficacy in conjunction with reduced side effects of intranasal nanotherapies in clinically relevant animal models, and to evaluate if intranasal-brain transport is viable in humans.…”