Fars K. Alanazi

Nanoemulsions as potential vehicles for transdermal and dermal delivery of hydrophobic compounds: an overview

Introduction: In recent years, nanoemulsions have been investigated as potential drug delivery vehicles for transdermal and dermal delivery of many compounds especially hydrophobic compounds in order to avoid clinical adverse effects associated with oral delivery of the same compounds. Droplet size and surface properties of nanoemulsions play an important role in the biological behavior of the formulation. Areas covered: In this review, current literature of transdermal and dermal delivery of hydrophobic compounds both in vitro as well as in vivo has been summarized and analyzed. Expert opinion: Nanoemulsions have been formulated using a variety of pharmaceutically acceptable excipients. In many cases of dermal and transdermal nanoemulsions, the skin irritation or skin toxicity issues on human beings have not been considered which needs to be evaluated properly. In the last decade, much attention has been made in exploring new types of nanoemulsion-based drug delivery system for dermal and transdermal delivery of many hydrophobic compounds. This area of research would be very advantageous for formulation scientists in order to develop some nanoemulsion-based formulations for their commercial exploitation and clinical applications.

The use of spray-drying to enhance celecoxib solubility

The present research investigates the enhancement of the dissolution rate of celecoxib by using spray-drying to prepare a solid dispersion with various polymers, namely Kollicoat IR® (Kollicoat), polyvinyl alcohol (PVA) 22000, or polyethylene glycol 6000 (PEG). The investigated drug-to-polymer mass ratios were 1:1, 1:2, and 1:4 by weight. Hydroalcoholic or methylene chloride solvent systems were used. The obtained yields ranged from 65% to 78%, whereas the entrapment efficiencies were between 68% and 82%. The results revealed an increase in the dissolution rate of the prepared particles up to 200% within 20 min. The prepared particles were investigated using differential scanning calorimetry, scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. The increased dissolution rate was attributed to hydrogen bond formation between celecoxib and each polymer together with the reduced size of the formed particles offering a greater overall surface area. It was concluded that spray-drying may be considered a successful one-step technique to improve the dissolution rate of celecoxib when using Kollicoat, PVA, or PEG as the carrier polymer.

Mucoadhesive Polymeric Hydrogels for Nasal Delivery of Acyclovir

The study evaluated different mucoadhesive polymeric hydrogels for nasal delivery of acyclovir. Gels containing poly-N-vinyl-2-pyrrolidone (PVP) were prepared with crosslinking achieved by irradiation with a radiation dose of 15 kGy being as efficient as 20 kGy. Gels containing chitosan and carbopol were also evaluated. The mucoadhesive properties of gels were measured by a modification of a classical tensile experiment, employing a tensile tester and using freshly excised sheep nasal mucosa. Considering the mucoadhesive force, chitosan gel and gel prepared with 3% PVP in presence of polyethylene glycol (PEG) 600 were the most efficient. The in vitro drug release depended on the gel composition. Higher release rates were obtained from PVP gels compared to chitosan or carbopol gels. The release rate of drug from PVP gels was increased further in presence of PEG or glycerol. Histopathological investigations proved that the PVP was a safe hydrogel to be used for mucosal delivery. The PEG in gel formulations caused less damages to the nasal mucosal compared to formulation containing glycerol.

Acyclovir Liposomes for Intranasal Systemic Delivery: Development and Pharmacokinetics Evaluation

Intranasal route is one of the most attractive routes for distributing drugs to systemic circulation. Liposomes are used as biocompatible carriers to improve delivery properties across nasal mucosa. The objective of the present study was to formulate acyclovir liposomes and partition into poly-N-vinyl-2-pyrrolidone. Entrapment efficiency showed that multilamellar and unilamellar liposomes were 43.2% ± 0.83 and 21% ± 1.01, respectively. The bioavailability of acyclovir from nasal mucoadhesive gel was 60.72% compared with intravenous route. The use of liposomes acyclovir and mucoadhesive gel not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity, but also facilitated direct absorption through the nasal mucosa.

Transdermal Delivery of Tadalafil. I. Effect of Vehicles on Skin Permeation

Transdermal delivery that avoids the presystemic disposition can provide an alternative to oral administration of tadalafil. Accordingly, the aim of this study was to select the best vehicle as the first step in optimization of tadalafil transdermal delivery. The vehicles were used neat or in selected binary combinations and were evaluated for drug solubilization and transdermal delivery. The drug solubility in pure vehicles were ranked as polyethylene glycol (PEG) 400 > propylene glycol (PG) > ethanol > ethyl oleate (EO) > isopropyl myristate (IPM) > water. The solubility in binary systems containing ethanol at 2:1 ratios with EO or IPM was greater than that obtained with pure ethanol, EO, or IPM. This effect could be due to the cosolvency effect. The transdermal drug delivery from pure vehicles was ranked as IPM > EO > ethanol > PG > PEG > water. The delivery from binary mixtures of ethanol with either IPM or EO was higher than that obtained from pure solvents with the delivery increasing with increasing ethanol concentration in the mixtures. The delivery from binary mixtures was synergistic rather than additive. The study thus demonstrated a potential of tadalafil transdermal delivery. Binary combinations of ethanol with either IPM or EO provided the first step forward toward the development of transdermal delivery system for tadalafil.

Preparation and Characterization of Spironolactone-Loaded Gelucire Microparticles Using Spray-Drying Technique

The basic objectives of this study were to prepare and characterize solid dispersions of poorly soluble drug spironolactone (SP) using gelucire carriers by spray-drying technique. The properties of the microparticles produced were studied by differential scanning calorimetry (DSC), scanning electron microscopy, saturation solubility, encapsulation efficiency, and dissolution studies. The absence of SP peaks in DSC profiles of microparticles suggests the transformation of crystalline SP into an amorphous form. The in vitro dissolution test showed a significant increase in the dissolution rate of microparticles as compared with pure SP and physical mixtures (PMs) of drug with gelucire carriers. Therefore, the dissolution rate of poorly water-soluble drug SP can be significantly enhanced by the preparation of solid dispersion using spray-drying technique.

Low density lipoprotein bionanoparticles: From cholesterol transport to delivery of anti-cancer drugs

In this review article, we highlight the importance of low-density lipoprotein (LDL) and its implications in the field of drug delivery to cancer cells. LDL is naturally occurring bionanoparticles (BNP) with a size of 18–25 nm. These BNPs specifically transport cholesterol to cells expressing the LDL receptors (LDLRs). Several tumors overexpress LDLRs, presumably to provide cholesterol for sustaining a high rate of membrane synthesis. LDL BNPs are biocompatible and biodegradable, favorably bind hydrophobic and amphiphilic drugs, are taken up by a receptor-mediated mechanism, have a half-life of 2–4 days, and can be rerouted. Drugs can be loaded onto LDL BNPs by surface loading, core loading, and apoprotein interaction. LDL may be used as a drug carrier for treatment of atherosclerosis, cancer, and in photodynamic therapies.

Microwave Irradiation-Assisted Synthesis of a Novel Crown Ether Crosslinked Chitosan as a Chelating Agent for Heavy Metal Ions (M +n )

Microwave irradiation was used to obtain a di-Schiff base type crosslinked chitosan dibenzocrown ether (CCdBE) via the reaction between the –NH2 and –CHO groups in chitosan and 4,4′-diformyldibenzo-18-c-6, respectively. The structure of the synthesized compound was characterized by elemental analysis, solid state 13C-NMR and FT-IR spectra analysis. The results showed that the mass fraction of nitrogen in the CCdBE derivative was much lower than those of chitosan. The FT-IR spectra of CCdBE revealed the expected chitosan-crown ether structure, as evidenced by the presence of the characteristic C=N and Ar peaks. The adsorption properties of CCdBE for Pd2+ and Hg2+ were investigated and the results demonstrated that the adsorbent has both desirable adsorption properties with a high particular adsorption selectivity for Hg2+ when in the presence of Pb2+ as well as selectivity coefficients for metal ions of KHg2+/Pb2+ = 8.00 and KHg2+/Pb2+ = 10.62 at pH values of 4 and 6, respectively. The reusability tests for CCdBE for Pb2+ adsorption showed that complete recovery of the ion was possible with CCdBE after 10-multiple reuses while CTS had no reusability at acidic solution because of its higher dissolution. The studied features of CCdBE suggested that the material could be considered as a new adsorbent. It is envisaged that the crosslinking of CTS into CCdBE would enhance practicality and effectiveness of adsorption in ion separation and removal procedures.

Sponge-Like: A New Protocol for Preparing Bacterial Ghosts

Bacterial Ghosts (BGs) received an increasing interest in the recent years for their promising medicinal and pharmaceutical applications. In this study, for the first time we introduce a new protocol for BGs production. E. coli BL21 (DE3) pLysS (Promega) was used as a model to establish a general protocol for BGs preparation. The protocol is based on using active chemical compounds in concentrations less than the Minimum Inhibition Concentration (MIC). Those chemical compounds are SDS, NaOH, and H2O2. Plackett-Burman experimental design was used to map the best conditions for BGs production. Normal and electronic microscopes were used to evaluate the BGs quality (BGQ). Spectrophotometer was used to evaluate the amount of the released protein and DNA. Agarose gel electrophoresis was used to determine the existence of any residue of DNA after each BGs preparation. Viable cells, which existed after running this protocol, were subjected to lysis by inducing the lysozyme gene carried on pLysS plasmid. This protocol is able to produce BGs that can be used in different biotechnological applications.

Novel Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Oral Delivery of Cinnarizine: Design, Optimization, and In-Vitro Assessment

Due to its extreme lipophilicity, the oral delivery of cinnarizine (CN) encounters several problems such as poor aqueous solubility and pH-dependent dissolution, which result in low and erratic bioavailability. The current study aims to design self-nanoemulsifying drug delivery systems (SNEDDS) of CN that circumvent such obstacles. Equilibrium solubility of CN was determined in a range of anhydrous and diluted lipid-based formulations. Dynamic dispersion tests were carried out to investigate the efficiency of drug release and magnitude of precipitation that could occur upon aqueous dilution. Droplet sizes of selected formulations, upon (1:1,000) aqueous dilution, were presented. The optimal formulations were enrolled in subsequent dissolution studies. The results showed that increasing lipid chain length and surfactant lipophilicity raised the formulation solvent capacity, while adding co-solvents provoked a negative influence. The inclusion of mixed glycerides and/or hydrophilic surfactants improved the drug release efficiency. Generally, no significant precipitation was observed upon aqueous dilution of the formulations. Five formulations were optimal in terms of their superior self-emulsifying efficiency, drug solubility, dispersion characteristics, and lower droplet size. Furthermore, the optimal formulations showed superior dissolution profile compared to the marketed (Stugeron®) tablet. Most importantly, they could resist the intensive precipitation observed with the marketed tablet upon shifting from acidic to alkaline media. However, SNEDDS containing medium-chain mixed glycerides showed the highest drug release rate and provide great potential to enhance the oral CN delivery. Accordingly, the lipid portion seems to be the most vital component in designing CN self-nanoemulsifying systems.