Current Drug Delivery - Volume 16, Issue 8, 2019

In vitro lipolysis has emerged as a powerful tool in the development of in vitro in vivo correlation for Lipid-based Drug Delivery System (LbDDS). In vitro lipolysis possesses the ability to mimic the assimilation of LbDDS in the human biological system. The digestion medium for in vitro lipolysis commonly contains an aqueous buffer media, bile salts, phospholipids and sodium chloride. The concentrations of these compounds are defined by the physiological conditions prevailing in the fasted or fed state. The pH of the medium is monitored by a pH-sensitive electrode connected to a computercontrolled pH-stat device capable of maintaining a predefined pH value via titration with sodium hydroxide. Copenhagen, Monash and Jerusalem are used as different models for in vitro lipolysis studies. The most common approach used in evaluating the kinetics of lipolysis of emulsion-based encapsulation systems is the pH-stat titration technique. This is widely used in both the nutritional and the pharmacological research fields as a rapid screening tool. Analytical tools for the assessment of in vitro lipolysis include HPLC, GC, HPTLC, SEM, Cryo TEM, Electron paramagnetic resonance spectroscopy, Raman spectroscopy and Nanoparticle Tracking Analysis (NTA) for the characterization of the lipids and colloidal phases after digestion of lipids. Various researches have been carried out for the establishment of IVIVC by using in vitro lipolysis models. The current publication also presents an updated review of various researches in the field of in vitro lipolysis.

Many drugs have been designed to treat diseases of the central nervous system (CNS), especially neurodegenerative diseases. However, the presence of tight junctions at the blood-brain barrier has often compromised the efficiency of drug delivery to target sites in the brain. The principles of drug delivery systems across the blood-brain barrier are dependent on substrate-specific (i.e. protein transport and transcytosis) and non-specific (i.e. transcellular and paracellular) transport pathways, which are crucial factors in attempts to design efficient drug delivery strategies. This review describes how the blood-brain barrier presents the main challenge in delivering drugs to treat brain diseases and discusses the advantages and disadvantages of ongoing neurotherapeutic delivery strategies in overcoming this limitation. In addition, we discuss the application of colloidal carrier systems, particularly nanoparticles, as potential tools for therapy for the CNS diseases.

Prostate cancer (PCa) is a worldwide issue, with a rapid increase in its occurrence and mortality. Over the years, various strategies have been implemented to overcome the hurdles that exist in the treatment of PCa. Consistently, there is a change in opinion about the methodologies in clinical trial that have engrossed towards the treatment of PCa. Currently, there is a need to resolve these newly recognized challenges by developing newer rational targeting systems. The ongoing clinical protocol for the therapy using different targeting systems is undertaken followed by local targeting to cancer site. A number of new drug targeting systems like liposomes, nanoemulsions, magnetic nanoparticles (MNPs), solid lipid nanoparticles, drug-peptide conjugate systems, drug-antibody conjugate systems, epigenetic and gene therapy approaches, and therapeutic aptamers are being developed to suit this protocol. Recent advancements in the treatment of PCa with various nanocarriers have been reported with respect to newly identified biological barriers and intended to solve the contexts. This review encompasses the input of nanotechnology in particular targeting of PCa which might escape the lifethreatening side effects and potentially contribute to bring fruitful clinical outcomes.

Background: Carbapenem-resistant Acinetobacter baumannii (A. baumannii) was on the top of the list of the most threatening bacteria published by the WHO in 2017. Antisense oligonucleotides (ASOs) based therapy is a promising strategy for combating Multi-Drug Resistant (MDR) bacteria because of its high specificity, easy design and lower induction of resistance, but poor cellular uptake by bacteria has restricted the further utilization of this therapy. Methods: Here, we used CADY, a secondary amphipathic peptide of 20 residues that could successfully carry siRNA into mammalian cells, to prepare CADY/ASOs nanoparticles (CADY-NPs) targeting acpP (encoding acyl carrier protein), and evaluated the uptake features, the inhibitory effects of CADY-NPs on gene expression and the growth of MDR-A. baumannii. Results: We found that CADY-NPs could be quickly internalized by drug-sensitive and MDR-A. baumannii in an energy independent manner, which could be restrained by chlorpromazine (an inhibitor of clathrin mediated endocytosis) significantly. In addition, CADY-NPs targeting acpP concentrationdependently retarded the growth of MDR-A. baumannii, which was associated with the decreased expression of targeted genes in A. baumannii. Conclusion: In conclusion, our research is the first to demonstrate that CADY can deliver ASOs into bacteria and provide a novel strategy for the treatment of MDR-A. baumannii.

Purpose: To clarify the inner framework and relative properties in vitro of Lyotropic liquid crystal (LLC) based on various prescriptions by using hydrophilic sinomenine hydrochloride (SH) and lipophilic cinnamaldehyde (CA) as model drugs. Methods: Phase structures were checked by polarized light microscopy (PLM) and small-angle X-ray scattering (SAXS). Rheological studies and Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) analysis were carried out to reveal their molecular interactions. In vitro release and skin permeation were conducted by Franz diffusion cell. Results: PLM and SAXS showed double diamond cubic crystal. All the samples displayed characteristics of non-Newtonian fluid, and the molecular interactions increased with the reducing water. ATRFTIR showed that the strongest strength of hydrogen bond emerged in the formulation with 32% water. Released SH of S2 and S3 arrived over 80%, while S1 only reached 45%, and that of CA was about 23%. Water-rich prescription gave higher percutaneous penetration for hydrophilic drugs, whereas no significant difference existed in CA permeation. Conclusion: Proportion of Phytantriol to water determined the LLC assembling and affected the dissolving status of hydrophilic substance, thereby impacting on the location sites of guest molecular interactions among the substances, rheology properties, and finally the release and penetration behavior in vitro. Adjusting the basic prescription was the key to obtain satisfactory percutaneous delivery and stability for LLC carrying multi-therapeutic agents.

Background: Curcumin has shown considerable pharmacological activity, including antiinflammatory activity. Nevertheless, the pharmacological effect of curcumin may be limited because of poor water solubility, metabolizing rapidly and systemic elimination. Objective: In the current research, a novel curcumin nanoemulsion (Cur-NE) was developed for improving in vitro permeability and bioavailability via pulmonary administration. Methods: The Cur-NE was prepared by a modified emulsification-evaporation method and its surfac morphology, particles size and distribution, and encapsulation efficiencies of drug in NE were characterized. In vitro transmembrane transport experiment was performed to investigate the transport profile of curcumin across Xenopus alveolar membrane. The pharmacokinetics of Cur-NE in rabbits was evaluated. Results: The average particles size, zeta potential, polydispersity index of Cur-NE were 234.8±1.08 nm, -19.5±0.2 mV and 0.10, respectively. Xenopus alveolar membrane was used in the transmembrane transport study, the cumulative amount of curcumin was 6.6% for curcumin suspensions, but nearly 50% for Cur-NE at the time of 8 h (P<0.05). The pharmacokinetic study in rabbits, the absolute bioavailability of curcumin for Cur-NE was 24.11%. Conclusion: Thus, a novel Cur-NE for pulmonary drug delivery was developed for improving in vitro permeability and bioavailability, which can be an alternate to the oral administration.

Background: Coenzyme Q10 is a fundamental endogenous factor involved in cell energy production that shows protective properties in oxidative stress, mainly in skeletal and heart muscle. Coenzyme Q10 supplementation appears to benefit athletes in strenuous training and in the elderly, demonstrating ant-inflammatory properties by reducing inflammatory cytokines. Improved absorption of coenzyme Q10 via a new delivery system would represent an important step forward in the use of coenzyme Q10 as a dietary supplement. Objective: The aim of the study was to evaluate the solubility and oral absorption in human healthy volunteers of a new food grade coenzyme Q10 phytosome formulation. Methods: Solubility studies were performed in vitro in simulated gastrointestinal fluids; human studies were conducted in healthy volunteers to evaluate oral absorption in a Single dose study, in comparison with the coenzyme Q10 capsules, and in a repeated study at two increasing doses. Results: The highest solubility shown by coenzyme Q10 phytosome in simulated intestinal fluids results in an improvement in oral absorption of coenzyme Q10 in healthy volunteers, three times more than the coenzyme Q10 according to AUC (area under the time/concentration curve) values. When two increasing doses (one and two capsules) were administered to healthy volunteers within a two-week schedule, the plasmatic levels of coenzyme Q10 resulted in 0.864±0.200 μg/ml (Mean±S.D.+41%) and 1.321±0.400 μg/ml (+116%), respectively versus baseline (0.614±0.120 μg/ml one capsule, 0.614±0.160 μg/ml two capsules). This detected dose-related bioavailability of coenzyme Q10 phytosome was even observed with no alterations in vital signs, neither in the physical examination nor in ECG, and no changes of clinical and biochemical parameters were observed. Conclusion: These findings, taken together, support the safety profile and significantly improved coenzyme Q10 oral absorption in humans with this new phytosome delivery formulation.

Objective: The aim of this study was to develop a new dosage form as an alternative to the classical tablet forms of atorvastatin calcium (AtrCa). The formulation strategy was to prepare an optimum self micro emulsifying drug delivery system (SMEDDS) to overcome the problem of low solubility of the active substance. Methods: In this study, pseudo ternary phase diagrams were plotted determined by the solubility studies. According to the solubility studies; oleic acid was used as the oil phase, Tween 20 and Span 80 were used as the surfactants and ethanol was used as the co-surfactant. SMEDDS formulations were characterized according to pH, electrical conductivity, density, refractive index, viscosity, emulsification time, dispersibility, robustness of dilution stability, droplet size, polidispersity index, zeta potential, transmittance %, cloud point, content quantification %, chemical and physical stability. The lipolysis study was conducted under fed and fasted conditions. In vitro release studies and kinetic evaluation were carried out. Permeability studies were also examined with Caco-2 cell culture. Results: The droplet size of the optimized formulation did not change significantly in different medias over the test time period. Improved SMEDDS formulation will progress steadily without precipitating along the gastrointestinal tract. Lipolysis studies showed that the oil solution had been exposed to high amount of lipolysis compared to the SMEDDS formulation. The release rate of AtrCa from AtrCa- SMEDDS formulation (93.8%, at 15 minutes) was found as increased when the results were compared with commercial tablet formulation and pure drug. The permeability value of AtrCa from AtrCa- SMEDDS formulation was found higher than pure AtrCa and commercial tablet formulation, approximately 9.94 and 1.64 times, respectively. Conclusion: Thus, lipid-based SMEDDS formulation is a potential formulation candidate for lymphatic route in terms of the increased solubility of AtrCa.