Nebulised Isotonic Hydroxychloroquine Aerosols for Potential Treatment of COVID-19

The coronavirus disease 2019 (COVID-19) is an unprecedented pandemic that has severely impacted global public health and the economy. Hydroxychloroquine administered orally to COVID-19 patients was ineffective, but its antiviral and anti-inflammatory actions were observed in vitro. The lack of efficacy in vivo could be due to the inefficiency of the oral route in attaining high drug concentration in the lungs. Delivering hydroxychloroquine by inhalation may be a promising alternative for direct targeting with minimal systemic exposure. This paper reports on the characterisation of isotonic, pH-neutral hydroxychloroquine sulphate (HCQS) solutions for nebulisation for COVID-19. They can be prepared, sterilised, and nebulised for testing as an investigational new drug for treating this infection. The 20, 50, and 100 mg/mL HCQS solutions were stable for at least 15 days without refrigeration when stored in darkness. They were atomised from Aerogen Solo Ultra vibrating mesh nebulisers (1 mL of each of the three concentrations and, in addition, 1.5 mL of 100 mg/mL) to form droplets having a median volumetric diameter of 4.3–5.2 µm, with about 50–60% of the aerosol by volume < 5 µm. The aerosol droplet size decreased (from 4.95 to 4.34 µm) with increasing drug concentration (from 20 to 100 mg/mL). As the drug concentration and liquid volume increased, the nebulisation duration increased from 3 to 11 min. The emitted doses ranged from 9.1 to 75.9 mg, depending on the concentration and volume nebulised. The HCQS solutions appear suitable for preclinical and clinical studies for potential COVID-19 treatment.

Exogenous Fungal Endophthalmitis: Clues to Aspergillus Aetiology with a Pharmacological Perspective

Exogenous fungal endophthalmitis (EXFE) represents a rare complication after penetrating ocular trauma of previously unresolved keratitis or iatrogenic infections, following intraocular surgery such as cataract surgery. The usual latency period between intraocular inoculation and presentation of symptoms from fungal endophthalmitis is several weeks to months as delayed-onset endophthalmitis. Aspergillus spp., is the most common causative mould pathogen implicated in this ocular infection and early diagnosis and prompt antimicrobial treatment, concomitantly in most cases with expert surgical attention, reduce unfavorable complications and increase the possibility of eye function preservation. Topical, intravitreal and systemic antifungal molecules are the mainstay of a medical approach to the disease and azoles, polyenes and in particular cases echinocandins are the pharmacological classes most commonly used in clinical practice. This review discusses pharmacokinetics and pharmacodynamic of antifungal agents in their principal modes of administration with a focus on their ability to achieve high drug concentration in the vitreous and ocular tissues.

Intra-arterial chemotherapy for retinoblastoma: transradial and transfemoral approach

Intraarterial chemotherapy (IAC) for retinoblastoma has notably changed the natural history of the disease and stands as an encouraging example of selective drug delivery. Targeted drug delivery allows achieving a high drug concentration within target tissue along with low systemic concentration. This maintains a high safety profile along with a high efficacy rate (97%).1–4 Increasing experience, refinements of the technique, and positive results of IAC over the past decade have expanded the indications to deliver treatment to a larger population. The most recent improvement introduced in our practice was administering the therapy using the transradial approach. Herein, we demonstrate the technique for IAC using both the transradial and transfemoral approach (video 1).

Evaluation of Paclitaxel Nanocrystals In Vitro and In Vivo

We created a novel paclitaxel (PTX) nanoparticle drug delivery system and compared this to acommercial injection preparation to evaluate the antitumor effects for both formulations in vivo and in vitro.PTXnanocrystals were 194.9 nm with potential of −29.6 mV. Cytotoxicity tests indicated that both formulations had similar effects and cytotoxicity was dose- and time-dependent.Pharmacodynamics indicated that the drug concentration at the tumor was greater with PTX nanocrystals compared to commercial injection (P<0.01) and that drug accumulated more and for a longer duration. In vivo antitumor evaluation indicated significant antitumor effects and low toxicity of PTX nanocrystals. Moreover, bioimaging indicated that the PTX retention time in MCF-7-bearing mice was longer, especially at the tumor site, and this high drug concentration was maintained for a long time.Overall, PTX nanocrystalsare feasible and superior to traditional injection formulation chemotherapy.

Mucoadhesive drug delivery system: an overview

The major objective of any dosage form is to deliver an optimum therapeutic amount of active agent to the proper site in the body to attain constant & maintenance of the desired drug concentration. Mucoadhesive drug delivery systems are effective delivery systems with various advantages as compared to other oral controlled release dosage forms in terms of drug delivery at specific sites with prolonged retention time of drugs at target sites. The main advantage of these systems includes avoiding first pass metabolism of the drugs and hence availability of high drug concentration at target site. Oral mucoadhesive systems have potential ability for controlled and extended release profile so as to get better performance and patient compliance. The present manuscript briefly reviews the benefits of mucoadhesive drug delivery systems, mechanisms involved in mucoadhesion, different factors affecting mucoadhesive drug delivery systems.

Mesoscale Simulation of Drug Molecules Distribution in the Matrix of Konjac Glucomannan (KGM) at Varying Drug Concentrations

Dissipative particle dynamics (DPD) is used in this work to simulate the distribution of carmustine (BCNU) molecules in konjac glucomannan (KGM) as potential drug carrier. It is shown from DPD simulation that the aggregated morphology of KGM differs at varying BCNU concentration levels. At 1 mol % of BCNU the phase aggregates as spherical particles, and at 5 mol% of BCNU, some BCNU molecules were partially uncovered by KGM molecules due to high drug concentration. However, even at higher concentration, most of the BCNU molecules are distributed in the inner area of the matrix, indicating that KGM interacts with BCNU well and it is a promising drug carrier for BCNU in water. DPD simulations may provide a powerful tool for designing drug delivery systems.

Stimulatory effect of the 2-palmitamidoethyl ester of adenosine 5'-phosphate on the activity of rabbit skeletal muscle protein kinase

2-Palmitamidoethyl ester of adenosine 5'-phosphate (PEA-AMP) stimulates the rabbit skeletal muscle protein kinase in relatively narrow range of high drug concentration. Mechanism of this effect seems to be analogous to that of cyclic AMP.