Pharmaceutical Nanotechnology - Volume 9, Issue 3, 2021

Background: Lipid-based systems such as self-nanoemulsifying drug delivery systems (SNEDDS) have resurged the eminence of nanoemulsions and offer many useful drug delivery opportunities. In the modern drug discovery era, there is a constant increase in the number of poorly soluble new chemical entities that suffer from poor and erratic bioavailability problems. The oral route possesses some major disadvantages, such as lack of constant drug levels in plasma, firstpass metabolism, which results in poor bioavailability. To address these problems, various lipidbased therapeutic systems are available from which self-enanoemulsifying systems have the potential to increase the bioavailability of poorly soluble drugs. Methods: SNEDDS is the isotropic mixture of oils, surfactant, and co-surfactant having droplet size in the range of 100-200 nm, which spontaneously emulsifies when it contacts with aqueous media in gastrointestinal (G.I) fluid. Various preparative methods are available for SNEDDS, such as high-pressure homogenizer, microfluidization, sonication, phase inversion, and shear state methods. These methods show favorable benefits in drug delivery. Self-nanoemulsifying drug delivery system possesses some disadvantages like precipitation of drug in G.I fluid or possible drug leaving in the capsule dosage form due to incompatibility issues, which can be overcome by more advanced techniques like supersaturated SNEDDS containing a precipitation inhibitor or Solid SNEDDS. These areformulated either through spray drying or using a solid carrier. Conclusion: The lipid-based nanocarrier (SNEDDS) plays a significant role in drug delivery to overcome the poor solubility and oral bioavailability. This review highlights the elaborative aspects of the diverse advantages of SNEDDS based formulations.

Background: Enhanced utilization of certain drugs may be possible through the development of alternative delivery forms. It has been observed that NSAIDs have adverse gastrointestinal tract effects such as irritation and ulceration during anti-inflammatory therapy. This challenge may be overcome through nano topical formulations. Objective: This study aimed to explore the potentials of a transdermal nanovesicular formulation for safe and enhanced delivery of piroxicam (PRX), a poorly water-soluble NSAID. Methods: Preformulation studies were conducted using DSC and FTIR. Ethosomal nanovesicular carrier (ENVC) was prepared by thin-film deposition technique using Phospholipon® 90 H (P90H) and ethanol and then converted into gel form. The formulation was characterized using a commercial PRX gel as control. Permeation studies were conducted using rat skin and Franz diffusion cell. Samples were assayed spectrophotometrically, and the obtained data was analyzed by ANOVA using GraphPad Prism software. Results: The preformulation studies showed compatibility between PRX and P90H. Spherical vesicles of mean size 343.1 ± 5.9 nm, and polydispersity index 0.510 were produced, which remained stable for over 2 years. The optimized formulation (PE30) exhibited pseudoplastic flow, indicating good consistency. The rate of permeation increased with time in the following order: PE30 > Commercial, with significant difference (p< 0.05). It also showed higher inhibition of inflammation (71.92 ± 9.67%) than the reference (64.12 ± 7.92%). Conclusion: ENVC gel of PRX was formulated. It showed potentials for enhanced transdermal delivery and anti-inflammatory activity relative to the reference. This may be further developed as a safe alternative to the oral form.

Background: Silver nanoparticles have been widely used in the field of nanomedicine. A comprehensive understanding of their pharmacokinetics is crucial for proper risk assessment and safe biomedical applications. Objectives: The purpose of this study was to investigate the safety of silver nanoparticles by determining their potential toxicity following 28 days of administration in Sprague-Dawley rats. Methods: The silver nanoparticles were administered by intravenous injection at the doses of 100, 200 and 500 μg/kg body weight for 28 consecutive days. Animals in the control group were received sterile water for injection. Each group consists of 10 male and 10 female rats. Results: No treatment-related effects were seen in any of the parameters monitored in rats given 100, 200 and 500 μg/kg body weight/day of silver nanoparticles. Conclusion: The study proved that the use of up to 500 μg/kg body weight biosynthesized silver nanoparticles have no toxic effect on the target organs and found safe. However, the safety of the nanoparticles might be attributed to the covering of biological moieties on nanoparticles. Hence, the biofunctionalized nanoparticles can be safely used by selecting the required size and dose in medicines and drug delivery systems.

Background: Metformin (MF) is an antidiabetic drug that belongs to class III of the biopharmaceutical classification system (BCS) characterized by high solubility and low permeability. Objective: The study aimed to prepare metformin as nanostructured lipid carriers (MF-NLCs) to control the drug release and enhance its permeability through the biological membrane. Methods: 2² full factorial design was used to make the design of MF-NLCs formulations. MFNLCs were prepared by hot-melt homogenization-ultra sonication technique using beeswax as solid lipid in the presence of liquid lipid (either capryol 90 or oleic acid) and surfactant (either poloxamer 188 or tween 80). Results: The entrapment efficiency (EE%) of MF-NLCs was ranged from 85.2±2.5 to 96.5±1.8%. The particle size was in the nanoscale (134.6±4.1 to 264.1±4.6 nm). The value of zeta potential has a negative value ranged from -25.6±1.1 to -39.4±0.9 mV. The PDI value was in the range of 0.253±0.01 to 0.496±0.02. The cumulative drug release was calculated for MF-NLCs and it was found that Q12h ranged from 90.5±1.7% for MF-NLC1 to 99.3±2.8 for MF-NLC4. Infra-red (IR) spectroscopy and differential scanning calorimetry (DSC) studies revealed the compatibility of the drug with other ingredients. MF-NLC4 was found to be the optimized formulation with the best responses. Conclusion: 2² full factorial design succeed to obtain an optimized formulation which controls the drug release and increases the drug penetration.

Background: Curcumin is a well-documented bioactive compound present in Curcuma sp., a tropical, medicinal plant. This substance exhibits broad-spectrum biological activities, including antivirus. Despite the lack of pharmaceutical properties of curcumin limits its clinical use. Objective: This study aims to produce curcumin nanoemulsion with different surface charge (curcumin (+) nanoemulsion and curcumin (-) nanoemulsion) and to evaluate its physical characteristics, in vitro cell cytotoxicity, and antiviral activity against dengue virus (DENV) 1 and 2. Methods: Two forms of nanoemulsion were prepared, which were differed from their surface charge through spontaneous procedure resulting in similar characteristics except for the zeta potential value. Cytotoxicity was determined using the RT-PCR method in the A549 cell line, and anti- DENV properties were determined by calculation of inhibitory concentration 50 (IC50) value. Results: The positive charge of curcumin-loaded nanoemulsion showed a better effect in reducing the viral replication represented by a lower IC50 value. In addition, DENV-1 was more sensitive and responsive to curcumin as compared to DENV-2. Conclusion: Positive surface charge of curcumin-loaded nanoemulsion improves the antiviral effect of the curcumin, suggesting a promising approach for alternative treatment for dengue virus infection.

Background: Tamoxifen is widely used for the treatment of estrogen receptor-positive breast cancer. However, it is associated with severe side effects of cancerous proliferation on the uterus endometrium. The tumor-targeting formulation strategies can effectively overcome drug side effects of tamoxifen and provide safer drug treatment. Objective: This study aimed to design tumor-targeted PLGA nanoparticles of tamoxifen by attaching hyaluronic acid (HA) as a ligand to actively target the CD44 receptors present at breast cancer cells surface. Methods: PLGA-PEG-HA conjugate was synthesized in the laboratory, and its tamoxifen-loaded nanoparticles were fabricated and characterized by FTIR, NMR, DSC, and XRD analysis. Formulation optimization was done by Box-Behnken design using Design-Expert software. The formulations were evaluated for in vitro drug release and cytotoxic effect on MCF-7 cell lines. Results: The particle size, PDI, and drug encapsulation efficiency of optimized nanoparticles were 294.8, 0.626, and 65.16%, respectively. Optimized formulation showed 9.56% burst release and sustained drug release for 8h. The drug release was affected by non-Fickian diffusion process and supplemented further by the erosion of polymeric matrix which followed the Korsmeyer-Peppas model. MTT cell line assay showed 47.48% cell mortality when treated with tamoxifen-loaded PLGA- PEG-HA nanoparticles. Conclusion: Hyaluronic acid conjugated PLGA-PEG nanoparticles of tamoxifen were designed for active targeting to cancerous breast cells. The results of the MTT assay showed that tamoxifen nanoparticles formulation was more cytotoxic than tamoxifen drug alone, which is attributed to their preferential uptake by cell lines by the affinity of CD44 receptors of cell lines to HA ligand present in nanoparticles.

Background: Amphotericin B (AMB) is water-insoluble polyene, which has a broad spectrum of antifungal activity. The hydrophobic drug only exits in the phospholipid bilayer, leading to a low-drug liposomal loading capacity. Objectives: This study is designed to prepare water-soluble inclusion complex (IC) between AMB and cyclodextrin (CD) to formulate liposomal vesicles, double-loaded with drug molecules in the phospholipid bilayer and AMB/CD IC in the aqueous core. Methods: Water-soluble AMB/CD IC was prepared by pH adjustment of the aqueous media and consequently characterized by scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). Liposomes double-loaded with AMB were formulated by the thin-film hydration method and accordingly evaluated for vesicle size, polydispersity index, entrapment efficiency, zeta potential, and in vitro drug leakage. Results: Hydroxypropyl β cyclodextrin (HP-β-CD) better solubilized AMB than both α-CD and β- CD e.g., the concentration of water-soluble AMB/HP-β-CD IC could reach 465 μg/mL. Both DSC and SEM data illustrated that the drug no longer existed in its crystalline form, in AMB/HP-β-CD IC. Liposomes double-loaded with hydrophilic AMB/HP-β-CD IC and hydrophobic AMB had a diameter of 270 nm, polydispersity index less than 0.27, and zeta potential ca.-42.8 mV. Moreover, liposomes double-loaded with AMB enhanced drug-liposomal loading capacity by 25%, less leaked drug in phosphate buffer pH 7.4 at 37°C in comparison to liposomes loaded with only hydrophobic AMB. Conclusion: Liposomes double-loaded with AMB and AMB/HP-β-CD IC increased drug-encapsulation ability and in vitro stability, suggesting potential drug delivery systems.

The authors wish to add words “Research Scholar” and “Research Supervisor” to their affiliations [1]. The original article can be found online at https://doi.org/10.2174/2211738506666180813122102