Drug Delivery Letters - Volume 14, Issue 4, 2024

Osteoarthritis (OA) is a degenerative joint disease resulting from the breakdown of joint cartilage and underlying bone. The most common symptoms of osteoarthritis are joint pain and stiffness. The major hurdle in its treatment is that the oral administration of NSAIDs (Lornoxicam) causes side effects like GI side effects, cardiovascular problems, liver issues, or renal problems. Thus, there is a need to develop a Transdermal drug delivery system for the transport of drugs, which reduces side effects and has several benefits over oral delivery, and a Novel drug delivery system to enhance the permeation of drugs and give relief from symptoms of OA.

This work deals with the formulation and evaluation of niosomal-loaded Transdermal Patches for the treatment of Osteoarthritis.

The Niosomes were prepared using the thin film hydration method, and Niosomal-loaded Transdermal patches were prepared using the Solvent Casting method. The preliminary evaluation and characterization studies were conducted to find the optimized formulation. The in-vitro release and ex-vivo permeation studies were investigated. Stability studies were also assessed.

The prepared Niosomes suspension (F2) was found to have particle size 320.2 nm, Zeta potential 23.9 mV, and Drug entrapment 79 ± 0.32%. The in-vitro drug release studies of optimized formulation show 96.44 ± 0.34% drug release for 24 hours. Then, the optimized Niosome formulation (F2) was loaded into the transdermal patches. The in-vitro permeation studies of Niosomal-loaded transdermal patch F1 (NLXTP) were performed, which showed a higher permeability than plain drug-loaded transdermal patch. F1 (NLXTP) followed Zero order release kinetic model, which shows a non-fickian controlled release diffusion mechanism. The ex-vivo drug release studies of optimized formulation F1 (NLXTP) show 2.79 ± 0.76 (µg/ml) drug permeated for 8 hours with a flux value of 0.35 ± 0.55, and the percentage of drug retention was found to be 5.67%. The stability studies showed that patches were stable over 90 days in different atmospheric conditions.

The Lornoxicam-loaded Niosomal transdermal patch was found to be a promising nano-drug-delivery alternative that showed better entrapment and release with a permeation profile for the daily management of osteoarthritis.

The research was carried out to develop the microemulsion-loaded gel of curcumin, alkylpolyglucoside, and tea tree oil to treat vulvovaginal candidiasis infection.

Screening of oils, surfactants, and co-surfactants was done based on solubility studies and the construction of pseudo-ternary phase diagrams with curcumin. The microemulsion was characterized for globule size, zeta potential, viscosity, and thermodynamic stability. Ex-vivo studies were carried out using Franz diffusion cells. The antifungal activity of microemulsion-loaded hydrogel was evaluated using the cup plate method using Candida albicans ATCC 10231 in glucose yeast agar medium.

The selected micro-emulsion consisted of curcumin 35µg/mL, IPM+TTO (1:1) 0.1 mL, Milcoside 100 + Acconon MC 8-2 EP NF 0.6-0.3 mL, phosphate buffer pH 4 160 mL showed maximum thermodynamic stability and exhibited lowest particle size and highest intensity. The viscosity of microemulsion-loaded gel was 11.2 pa.s. The surface tension of the microemulsion was measured by tensiometer and was found to be 26.07 mN/m. Antimicrobial susceptibility testing assay was done according to NCCLs assay protocol, and the EC50 value of our formulation was found to be 0.4465 μg/mL. In-vitro drug release and ex-vivo permeation studies showed 67.9% release in 420 minutes and 83.02% release in 360 minutes, respectively. An in-vitro irritation study concluded that there was no redness or irritation on goat mucosa.

The texture analysis test showed adhesiveness at -172.46 g s at - 4.60 adhesive force, and the peak load was 13.40 g. The microemulsion-loaded gel formulation can be a promising alternative to the marketed formulations available for vaginal yeast infections.

Plasma protein binding is inevitable for nanomaterials injected into blood circulation. For liposomes, this process is affected by the lipid composition of the bilayer. Membrane constituents and their ratio define liposome characteristics, namely, surface charge and hydrophobicity, which drive protein adsorption. Roughly 30 years ago, the correlation between the amount of bound proteins and the resulting circulation time of liposomes was established by S. Semple, A. Chonn, and P. Cullis. Here, we have estimated ex vivo plasma protein binding, primarily to determine the impact of melphalan prodrug inclusion into bilayer on bare, PEGylated (stealth), and Sialyl Lewis X (SiaLe^X)-decorated liposomes.

Liposomes were allowed to bind plasma proteins for 15 minutes, then liposome-protein complexes were isolated, and protein and lipid quantities were assessed in the complexes. In addition, the uptake by activated HUVEC cells was evaluated for SiaLe^X-decorated liposomes.

Melphalan moieties on the bilayer surface enrich protein adsorption compared to pure phosphatidylcholine sample. Although PEG-lipid had facilitated a significant decrease in protein adsorption in the control sample, when prodrug was added to the composition, the degree of protein binding was restored to the level of melphalan liposomes without a stealth barrier. A similar effect was observed for SiaLe^X-decorated liposomes.

None of the compositions reported here should suffer from quick elimination from circulation, according to the cut-off values introduced by Cullis and colleagues. Nevertheless, the amount of bound proteins is sufficient to affect biodistribution, namely, to impair receptor recognition of SiaLe^X and reduce liposome uptake by endothelial cells.