vesicles have shown tremendous potential to overcome these hurdles and improve the local therapeutic effect of these drugs.

Objective: This review article is aimed to shed light on flexible nano-vesicular carriers as a means to combat skin diseases.

Methods: The literature was reviewed using PubMed database using various keywords such as liposomes, flexible (deformable liposomes) (transferosomes), ethosomes, transethosomes, niosomes, and spanlastics.

Results: Liposomes and niosomes were found effective for the loading and release of both hydrophilic and lipophilic drugs. However, their limited skin penetration led to drug delivery to the outermost layers of skin only. This necessitates the search for innovative vesicular carriers, including liposomes, flexible (deformable liposomes), ethosomes, transethosomes, and spanlastics. These flexible nano-vesicular carriers showed enhanced drug delivery and deposition across various skin layers, which was better than their corresponding conventional vesicles. This resulted in superior drug efficacy against various skin diseases such as skin cancer, inflammatory skin diseases, superficial fungal infections, etc.

Conclusion: Flexible nano-vesicular carriers have proven themselves as efficient drug delivery systems that are able to deliver their cargo into the deep skin layers and thus, improve the therapeutic outcome of various skin diseases. However, there remain some challenges that need to be addressed before these nanocarriers can be translated from the lab to clinics.

This study aimed to encapsulate voriconazole into nano-micelles of poly(ethylene glycol)- block-poly(ε-caprolactone) to enhance its antifungal activity and reduce the required doses. The nanomicelles were prepared at various drug/polymer ratios, and their various physicochemical properties were studied. The nano-micelles had a small particle size in the range of ~50-60 nm and homogenous size distribution. The nano-micelles had high encapsulation efficiency and loading capacity in the range of ~40-95% and ~20-27%, respectively. Both encapsulation efficiency and loading capacity could be modulated by changing the drug/polymer ratio. Voriconazole release from the nano-micelles was much slower than the drug solution. The drug release pattern was biphasic, with a relatively faster initial phase followed by a sustained release. The antifungal efficacy was evaluated in vitro against Aspergillus flavus and Candida albicans using the drug solution in dimethyl sulfoxide/water as a control. The inhibition zone diameters of the fungi increased with increasing the drug concentration. The diameter of the inhibition zones against Aspergillus flavus was comparable for the nano-micelles and control. In contrast, the nano-micelles had significantly wider inhibition zones against Candida albicans than the control. These results show that poly(ethylene glycol)-block-poly(ε-caprolactone) nano-micelles could be used as a promising delivery system to enhance voriconazole antifungal efficacy.

The aim of this study was to prepare triamcinolone acetonide (TA)-loaded poly(ethylene glycol)-blockpoly(e-caprolactone) (PEG-b-PCL) and poly(ethylene glycol)-block-poly(lactic acid) (PEG-b-PLA) micelles as a potential treatment of ocular inflammation. The micelles were evaluated for particle size, drug loading capacity and drug release kinetics. Selected micellar formulations were dispersed into chitosan hydrogel and their anti-inflammatory properties were tested in rabbits using a carrageenan-induced ocular inflammatory model. Particle size ranged from 59.44 ± 0.15 to 64.26 ± 0.55 nm for PEG-b-PCL and from 136.10 ± 1.57 to 176.80 ± 2.25 nm for PEG-b-PLA micelles, respectively. The drug loading capacity was in the range of 6–12% and 15–25% for PEG-b-PCL and PEG-b-PLA micelles, respectively and was dependent on the drug/polymer weight ratio. TA aqueous solubility was increased by 5- and 10-fold after loading into PEG-b-PCL and PEG-b-PLA micelles at a polymer concentration as low as 0.5 mg/mL, respectively. PEG-b-PLA micelles suspended in chitosan hydrogel were able to sustain the drug release where only 42.8 ± 1.6% drug was released in one week. TA/PEG-b-PLA micelles suspended in chitosan hydrogel had better anti-inflammatory effects compared with the plain drug hydrogel or the drug micellar solution. Complete disappearance of the corneal inflammatory changes was observed for the micellar hydrogel. These results confirm the potential of PEG-b-PLA micelles suspended in chitosan hydrogel to enhance the anti-inflammatory properties of triamcinolone acetonide.

Purpose: To develop an externally triggered rapid-release targeted system for treating ovarian cancer, gemcitabine (GMC) was entrapped into sonosensitive (SoS) folate (Fo)- modified liposomes (LPs). Methods: GMC-loaded LPs (GMC LPs), GMC-loaded Fo-targeted LPs (GMC-Fo LPs), and GMC-loaded Fo-targeted SoS LPs (GMC-SoS Fo LPs) were prepared utilizing a filmhydration technique and evaluated based on particle size, ζ-potential, and percentage entrapped drug. Cellular uptake of the fluorescent delivery systems in Fo-expressing ovarian cancer cells was quantified using flow cytometry. Finally, tumor-targeting ability, in vivo evaluation, and pharmacokinetic studies were performed. Results: GMC LPs, GMC-Fo LPs, and GMC-SoS Fo LPs were successfully prepared, with sizes of 0.05). Biodistribution study showed that of GMC concentration in tumors treated with GMC-SoS-Fo LPs (with ultrasound) improved 2.89-fold that of free GMC (p<0.05). In vivo, GMC-SoS Fo LPs showed the highest antiproliferative and antitumor action on ovarian cancer. Conclusion: These findings showed that externally triggered rapid-release SoS Fo-modified LPs are a promising system for delivering rapid-release drugs into tumors. Keywords: sonosensitive liposome, gemcitabine, folate-modified liposomes, externally triggered, ovarian cance

Abstract: Intravenous dexmedetomidine (DEX) is currently approved by the FDA for the sedation of intubated patients in intensive care units to reduce anxiety and to augment postoperative analgesia. Bradycardia and hypotension are limitations associated with the intravenous administration of DEX. In this study, DEX sublingual in situ gels were developed and assessed for their pH, gelling capacity, viscosity, mucoadhesion and in vitro drug release. The optimized gelling system demonstrated enhanced mucoadhesion, superior gelling capacity, reasonable pH and optimal rheological profile. In vivo, compared to the oral solution, the optimal sublingual gel resulted in a significant higher rate and extent of bioavailability. Although the in situ gel had comparable plasma levels to those observed following intravenous administration, significant amelioration of the systemic adverse reactions were attained. As demonstrated by the hot plate method, a sustained duration of analgesia in rats was observed after sublingual administration of DEX gel compared to the intravenously administered DEX solution. Furthermore, no changes in systolic blood pressure and heart rate were recorded in rats and rabbits, respectively, after sublingual administration of DEX. Sublingual administration of DEX in situ gel provides a promising approach for analgesia and sedation, while circumventing the reported adverse reactions associated with intravenous administration of DEX.

Loading small molecular weight hydrophilic drugs into polymeric carriers is a challenging task. Metformin hydrochloride (MET) is a highly soluble oral antidiabetic drug of small size and high cationic charge. Hydrophobic ion pairing (HIP) is an approach for reversible modulation of solubility and hydrophilicity of water-soluble drugs via complexation with oppositely charged molecules. Herein, we prepared MET ion pairs and carefully studied and characterized MET interaction with diferent ligands, with the aim of increasing MET lipophilicity and loading efciency. HIP was successful using three hydrophilic anionic ligands; sodium dodecyl sulphate (SDS) Carbopol (CB) and tannic acid (TA). Electrostatic interaction and hydrogen bonding drove the complexation per spectroscopic and thermal studies. Complexation efciency depended on ligand type and charge ratio. While complexes had varying interaction strengths, the excessive stability of TA/MET resulted in unfavorable poor MET dissociation. Notably, HIP imparted a 450 and tenfold lipophilicity increase for SDS/MET and CB/ MET, respectively. The latter showed favorable controlled, yet complete release of MET at pH 6.8 and was loaded into alginate beads. Complex bulkiness and decreased lipophilicity resulted in a dramatic 88% increase of MET loading, demonstrating the success of HIP as a simple, efcient and applicable approach for modulating drug’s properties.