Novel cubosome based system for ocular delivery of acetazolamide

Acetazolamide is the drug of choice for glaucoma treatment in an emergency. However, it is not available in any topical formulation and it is available only as systemic tablets. Despite its efficiency as a drug in decreasing intraocular pressure, it has negative systemic effects as renal toxicity and metabolic acidosis. Moreover, it suffers from poor aqueous solubility and low corneal permeability limiting its ocular bioavailability and its use topically. Cubosomes have enormous advantages as a drug delivery system, most importantly, high surface area, thermal stability, and ability to encapsulate hydrophobic, amhiphilic, and hydrophilic molecules. Herein, we have exploited the unique properties of cubosomes as a novel nano-delivery system for acetazolamide as eye drops dosage form for glaucoma treatment. Different acetazolamide-loaded cubosomes have been developed and evaluated. The best-optimized formulation (F5), was cubic shaped structure, with an average particle size of 359.5 ± 2.8 nm, surface charge −10.8 ± 3.2 mV, and 59.8% entrapment efficiency. Ex-vivo corneal permeation studies have revealed a 4-fold increase in acetazolamide permeability coefficient compared to that stated in the literature. F5 showed superior therapeutic efficacy represented by a 38.22% maximum decrease in intraocular pressure vs. 31.14 and 21.99% decrease for the commercial Azopt^® eye drops and Cidamex^® tablets, respectively. It also exhibited higher (AUC_0–10) compared to Azopt^® eye drops and Cidamex^® tablets by 2.3 and 3 times, respectively. F5 showed mean residence time 4.22 h vs. 2.36 and 2.62 h for Azopt^® and Cidamex^® with no eye irritation observed according to the modified Draize test. To the best of our knowledge, this is the first study for developing acetazolamide-loaded cubosomes as the topical delivery system for glaucoma treatment.     

General overview of lipid–polymer hybrid nanoparticles,dendrimers, micelles,liposomes, spongosomes and cubosomes

Introduction: In recent years, the wider use of nanotechnology has attracted greater attention from scientists in multi-disciplinary fields. Nanotechnological research has come a long way in the past decade, with major advances being made, both in terms of diagnostic and therapeutic potential of nanoparticles.

Areas covered: Some of the prominently discussed nanoparticles in this day and age are polymeric micelles, liposomes, lipid–polymer hybrid nanoparticles, dendrimers, spongosomes and cubosomes. This review attempts to focus on the conventional advantages and exemplary features that these particles possess, thus making them some of the most ideal vehicles for drug delivery.

Expert opinion: Particulate systems, which have been extensively studied in this article, have been employed to enhance the pharmacokinetic and pharmacodynamic characteristics of various hydrophobic and hydrophilic drug moieties, thus attempting to prolong the blood circulation times and increase their efficacy over unmodified drug molecules. These modification techniques have enabled these drug molecules to be delivered to the pharmacological sites of action at an optimised controlled rate, thus trying to minimise the potential for any toxicity resulting from the non-specific distribution of drug to various organs.     

Nanostructured liquid crystalline formulation as a remarkable new drug delivery system of anti-epileptic drugs for treating children patients

Purpose

Development of a new dosage-form of antiepileptic-drugs appropriated for children.

Etodolac transdermal cubosomes for the treatment of rheumatoid arthritis: ex vivo permeation and in vivo pharmacokinetic studies

In this study, transdermal etodolac-loaded cubosomes were developed in order to relieve patient pain and joints stiffness by providing stable etodolac concentration at the targeting sites through controlled drug delivery via the noninvasive skin route with more sustaining and less frequent dosing. Different ratios and percentages of poloxamer 407 and monoolein were used to formulate the cubosomes using emulsification and homogenization processes. The etodolac-loaded cubosomes showed particle size values ranging from 135.95 to 288.35?nm and zeta potential values ranging from ?18.40 to ?36.10?mV. All the cubosomes offered an encapsulation efficiency value of about 100% and showed drug loading capacity ranging from 1.28 to 6.09%. The in vitro drug release studies revealed a controlled drug release profile with a drug release rate up to 15.08%/h. Increasing poloxamer concentration in etodolac-loaded cubosomes resulted in nanoparticles with less particle size and faster drug release. The particles exhibited cubic and hexagonal shapes. The DSC and X-ray analysis demonstrated that the drug was encapsulated in the cubosomes bicontinuous structures in amorphous form. In addition, investigated cubosomes exhibited fast drug penetration through excited mice skin followed by slower drug penetration for up to 24?h. The pharmacokinetic study in human volunteers showed that the selected etodolac-loaded cubosomes enhanced the bioavailability of etodolac as compared to the oral capsules (266.11%) with evidence of longer half-life and higher MRT that reached 18.86 and 29.55?h, respectively. The etodolac-loaded cubosomes propose a promising system for treatment of arthritis simply through skin application.