Intratracheal Administration of Chloroquine-Loaded Niosomes Minimize Systemic Drug Exposure

Abstract

Pulmonary administration provides a useful alternative to oral and invasive routes of administration while enhancing and prolonging the accumulation of drugs into the lungs and reducing systemic drug exposure. In this study, chloroquine, as a model drug, was loaded into niosomes for potential pulmonary administration either via dry powder inhalation or intratracheally. Chloroquine-loaded niosomes have been prepared and extensively characterized. Furthermore, drug-loaded niosomes were lyophilized and their flowing properties were evaluated by measuring the angle of repose, Carr’s index, and Hausner ratio. The developed niosomes demonstrated a nanosized (100–150 nm) spherical morphology and chloroquine entrapment efficiency of ca. 24.5%. The FT-IR results indicated the incorporation of chloroquine into the niosomes, whereas in vitro release studies demonstrated an extended-release profile of the drug-loaded niosomes compared to the free drug. Lyophilized niosomes exhibited poor flowability that was not sufficiently improved after the addition of lactose or when cryoprotectants were exploited throughout the lyophilization process. In vivo, intratracheal administration of chloroquine-loaded niosomes in rats resulted in a drug concentration in the blood that was 10-fold lower than the oral administration of the free drug. Biomarkers of kidney and liver functions (i.e., creatinine, urea, AST, and ALT) following pulmonary administration of the drug-loaded nanoparticles were of similar levels to those of the control untreated animals. Hence, the use of a dry powder inhaler for administration of lyophilized niosomes is not recommended, whereas intratracheal administration might provide a promising strategy for pulmonary administration of niosomal dispersions while minimizing systemic drug exposure and adverse reactions.

Preparation and Characterization of Patch Loaded with Clarithromycin Nanovesicles for Transdermal Drug Delivery

“…As a result, F1 and F9 obeyed a first-order kinetic model, which stated that the drug release rate was proportional to the residual drug concentration in the system. Similar findings have been reported in previous studies [ 67 , 68 ]. For instance, Kulkarni et al [ 67 ] reported that a first-order model was determined to be the most appropriate model from the investigation of the release kinetics of hyaluronic-acid-loaded niosomes, as evidenced by an R 2 value of 0.99.…”

“…For instance, Kulkarni et al [ 67 ] reported that a first-order model was determined to be the most appropriate model from the investigation of the release kinetics of hyaluronic-acid-loaded niosomes, as evidenced by an R 2 value of 0.99. In another study, Saafan et al [ 68 ] showed that first-order kinetics provided the most accurate representation of drug release for a chloroquine–niosomal formulation.…”

Ultrasonic-Assisted Fabrication of MIL-100(Fe) Metal–Organic Frameworks as a Carrier for the Controlled Delivery of the Chloroquine Drug

“…The releasing speed in pH 2 was faster than that of the PBS solution. In the later stage, the remaining drug with a solid bond to the MIL-100(Fe) network was slowly released and only completely detached from the material after 80 h. 49 In this releasing stage, the chloroquine molecules diffused from inside of MIL-100(Fe) network into the solution, and at the end of the stage, the structural material was observed to be collapsed. This result is much slower than using the commercial chloroquine-containing drug with 100% release after 2 h. The XRD patterns of the MIL-100(Fe)@chloroquine system after releasing chloroquine in PBS and pH 2 are studied as shown in Figure 9a.…”

“…The releasing speed in pH 2 was faster than that of the PBS solution. In the later stage, the remaining drug with a solid bond to the MIL-100(Fe) network was slowly released and only completely detached from the material after 80 h. 49 In this releasing stage, the chloroquine molecules diffused from inside of MIL-100(Fe) network into the solution, and at the end of the stage, the structural material was observed to be collapsed. This result is much slower than using the commercial chloroquine-containing drug with 100% release after 2 h.…”

Development of Sedative Dexmedetomidine Sublingual In Situ Gels: In Vitro and In Vivo Evaluations

“…In vitro release studies were conducted in triplicates and the mean cumulative drug released was constructed as a function of time. The kinetics of drug release from the studied in situ gels were evaluated as reported previously [17,18].…”