Nanoparticle - Novel Drug Delivery System: A Review

For the past few years, there has been a considerable research on the basis of Novel drug delivery system, using particulate vesicle systems as such drug carriers for small and large molecules. Nanoparticles, Liposomes, Microspheres, Niosomes, Pronisomes, Ethosomes, Proliposomes have been used as drug carrier in vesicle drug delivery system. Nanotechnology refers to the creation and utilization of materials whose constituents exist at the nanoscale; and, by convention, be up to 100 nm in size.. Nanoparticles are being used for diverse purposes, from medical treatments, using in various branches of industry production such as solar and oxide fuel batteries for energy storage, to wide incorporation into diverse materials of everyday use such as cosmetics or clothes, optical devices, catalytic, bactericidal, electronic, sensor technology, biological labelling and treatment of some cancers. Various polymers have been used in the formation of Nanoparticles. Nanoparticles have been improving the therapeutic effect of drugs and minimize the side effects. Basically, Nanoparticles have been prepared by using various techniques as such dispersion of preformed polymers, polymerization of monomers and ionic gelation or coacervation of hydrophilic polymer. Nanoparticles have been evaluated by using parameters of drug entrapment efficiency, particle shape, drug release study. Keywords: Nanoparticles, Drug, novel, delivery

DIACEREIN-LOADED NIOSOMES (DC-NS): A NEW TECHNIQUE TO SUSTAIN THE RELEASE OF DRUG ACTION

Objective: The study's main goal is to develop a suitable niosomes (NS) encapsulated drug for anti-inflammatory effects such as diacerein (DC) and to evaluate the system's vesicle size (VS), entrapment efficiency (EE %), physical stability and in vitro release. Methods: Tween (40 and 60), cholesterol, and stearylamine were used in a 1:1:0.1 molar ratios as non-ionic surfactants. Thin film hydration was used to create the NS. Results: The higher EE% was observed with NS (F11) prepared from tween 60, cholesterol and 2.5 min sonication. These formulations' release patterns were Higuchi diffusion and first order. For the stability study, NS formulations were stored at temperature between 2-8 °C for 60 d retains the most drugs when compared to room and high temperature conditions. Conclusion: The findings of this study have conclusively shown that after NS encapsulation of DC, drug release is prolonged at a constant and controlled rate.

STATISTICAL OPTIMIZATION AND EVALUATION OF ETHOSOMAL MICONAZOLE NITRATE SUSPENSION

Objective: The objectives of the present study were to optimize and evaluate the ethosomal suspension of miconazole nitrate for the treatment of local and systemic fungal infections. Methods: Miconazole topical formulation is prepared for better patient compliance and to reduce the dose of a drug. Miconazole nitrate ethosomes were prepared by the cold method using factorial designing with Ethanol(X1), IPA(Isopropyl alcohol)(X2), and Lecithin(X3) as Independent variables and % EE(Entrapment efficiency)(Y1) and % DR(drug release at 8th h)(Y2) was selected as responses. Results: The results obtained in the design showed that there was no significant interaction among factors. The lecithin concentration had a positive response on % EE, while ethanol concentration and IPA had a positive effect. For % DR, Ethanol, and IPA showed a positive effect and Lecithin had a negative response. The formulation EM22 (3 ml X1,3 ml X2 and 300 mg of X3) characterized by high % EE(77.3 %) and optimum % DR(94.2%) and formulation EM6 (2 ml X1,2 ml X2 and 100 mg of X3) characterized by high % DR(97.32 %) and optimum % EE (74.8 %). EM22 was incorporated in the gel as it is showing more entrapment efficiency and compared with the marketed product for drug release. Conclusion: From the result, it was concluded that formulated ethosomal suspension and optimized gel have more drug release than marketed formulation so that formulated suspension can be used for the preparation of antifungal gels, creams, ointments for sustained release.

Design of Targeted Flurbiprofen Biomimetic Nanoparticles for Management of Arthritis: In Vitro and In Vivo Appraisal

Flurbiprofen (FLUR) is a potent non-steroidal anti-inflammatory drug used for the management of arthritis. Unfortunately, its therapeutic effect is limited by its rapid clearance from the joints following intra-articular injection. To improve its therapeutic efficacy, hyaluronic acid-coated bovine serum albumin nanoparticles (HA-BSA NPs) were formulated and loaded with FLUR to achieve active drug targeting. NPs were prepared by a modified nano-emulsification technique and their HA coating was proven via turbidimetric assay. Physicochemical characterization of the selected HA-BSA NPs revealed entrapment efficiency of 90.12 ± 1.06%, particle size of 257.12 ± 2.54 nm, PDI of 0.25 ± 0.01, and zeta potential of −48 ± 3 mv. The selected formulation showed in-vitro extended-release profile up to 6 days. In-vivo studies on adjuvant-induced arthritis rat model exhibited a significant reduction in joint swelling after intra-articular administration of FLUR-loaded HA-BSA NPs. Additionally, there was a significant reduction in CRP level in blood as well as TNF-α, and IL-6 levels in serum and joint tissues. Immunohistochemical study indicated a significant decrease in iNOS level in joint tissues. Histopathological analysis confirmed the safety of FLUR-loaded HA-BSA NPs. Thus, our results reveal that FLUR loaded HA-BSA NPs have a promising therapeutic effect in the management of arthritis.

PLGA/PEG Nanoparticles Loaded with Cyclodextrin-Peganum harmala Alkaloid Complex and Ascorbic Acid with Promising Antimicrobial Activities

Antimicrobial drugs face numerous challenges, including drug resistance, systemic toxic effects, and poor bioavailability. To date, treatment choices are limited, which warrants the search for novel potent antivirals, including those extracted from natural products. The seeds of Peganum harmala L. (Zygophyllaceae family) have been reported to have antimicrobial, antifungal, and anticancer activities. In the present study, a 2-hydroxy propyl-β-cyclodextrin (HPβCD)/harmala alkaloid-rich fraction (HARF) host–guest complex was prepared using a thin-film hydration method to improve the water solubility and bioavailability of HARF. The designed complex was then co-encapsulated with ascorbic acid into PLGA nanoparticles coated with polyethylene glycol (HARF–HPßCD/AA@PLGA-PEG NPs) using the W/O/W multiple emulsion-solvent evaporation method. The average particle size, PDI, and zeta potential were 207.90 ± 2.60 nm, 0.17 ± 0.01, and 31.6 ± 0.20 mV, respectively. The entrapment efficiency for HARF was 81.60 ± 1.20% and for ascorbic acid was 88 ± 2.20%. HARF–HPßCD/AA@PLGA-PEG NPs had the highest antibacterial activity against Staphylococcus aureus and Escherichia coli (MIC of 0.025 mg/mL). They also exhibited high selective antiviral activity against the H1N1 influenza virus (IC50 2.7 μg/mL) without affecting the host (MDCK cells). In conclusion, the co-encapsulation of HPCD–HARF complex and ascorbic acid into PLGA-PEG nanoparticles significantly increased the selective H1N1 killing activity with minimum host toxic effects.

Fabrication and Evaluation of Quercetin Nanoemulsion: A Delivery System with Improved Bioavailability and Therapeutic Efficacy in Diabetes Mellitus

The current study was intended to fabricate and evaluate ultrasonically assisted quercetin nanoemulsion (Que-NE) for improved bioavailability and therapeutic effectiveness against diabetes mellitus in rats. Ethyl oleate, Tween 20, and Labrasol were chosen as oil, surfactant, and cosurfactant, respectively. Box–Behnken design (BBD) was employed to study the influence of process variables such as % surfactant and cosurfactant mixture (Smix) (5 to 7%), % amplitude (20–30%) and sonication time (2.5–7.5 min) on droplet size, polydispersibility index (PDI), and % entrapment efficiency (%EE) were studied. The optimization predicted that 9% Smix at 25% amplitude for 2.5 min would produce Que-NE with a droplet size of 125.51 nm, 0.215 PDI, and 87.04% EE. Moreover, the optimized Que-NE exhibited appreciable droplet size and PDI when stored at 5, 30, and 40 °C for 45 days. Also, the morphological characterization by transmission electron microscope (TEM) indicated the spherical shape of the optimized nanoemulsion. Furthermore, the Que-NE compared to pure quercetin exhibited superior release and enhanced oral bioavailability. The streptozocin-induced antidiabetic study in rats revealed that the Que-NE had remarkable protective and therapeutic properties in managing body weight, blood glucose level, lipid profile, and tissue injury markers, alongside the structure of pancreatic β-cells and hepatocytes being protected. Thus, the developed Que-NE could be of potential use as a substitute strategy for diabetes.

Development of Inclusion Complexes With Relative Humidity Responsive Capacity as Novel Antifungal Agents for Active Food Packaging

Background: Allyl isothiocyanate is an excellent antimicrobial compound that has been applied in the development of active food packaging materials in the last years. However, the high volatility of this compound could prevent a lasting effect over time. In order to avoid this problem, cyclodextrin inclusion complexes have been proposed as an alternative, being beta-cyclodextrin (β-CD) as the main candidate. In addition, β-CD could act as a relative humidity-responsive nanoparticle. In this regard, the aim of this study was to develop inclusion complexes based on β-CD and AITC as relative humidity-responsive agents, which can be used in the design of active food packaging materials.Methods: Two different β-CD:AITC inclusion complexes (2:1 and 1:1 molar ratios) were obtained by the co-precipitation method. Entrapment efficiency was determined by gas chromatography, while inclusion complexes were characterized through thermal, structural, and physicochemical techniques. Antifungal capacity of inclusion complexes was determined in a headspace system. Furthermore, the AITC release from inclusion complexes to headspace at different percentages of relative humidity was evaluated by gas chromatography, and this behavior was related with molecular dynamic studies.Key Findings and Conclusions: The entrapment efficiency of inclusion complexes was over to 60%. Two coexisting structures were proposed for inclusion complexes through spectroscopic analyses and molecular dynamic simulation. The water sorption capacity of inclusion complexes depended on relative humidity, and they exhibited a strong fungicide activity against Botrytis cinerea. Furthermore, the AITC release to headspace occurred in three stages, which were related with changes in β-CD conformational structure by water sorption and the presence of the different coexisting structures. In addition, a strong influence of relative humidity on AITC release was evidenced. These findings demonstrate that β-CD:AITC inclusion complexes could be used as potential antifungal agents for the design of food packaging materials, whose activity would be able to respond to relative humidity changes.

Optimization and Evaluation of Piperine Loaded Herbosomes for their Antioxidant and Hepatoprotective Potential

Piperine is classified as a class II drug in the biopharmaceutical classification system due to its low aqueous solubility. As a result, piperine herbosomes were created to improve the dissolution rate and in vivo liver protecting activity of piperine and physico-chemical characteristics were used to confirm herbosome formation. The piperine-herbosome formulation revealed spherical particle size of all formulations from P1-P10 and found142.4 ± 0.98 nm for best piperine-herbosome formulation (P2) and a PDI value of 0.237, indicating a homogeneous population of piperine loaded vesicles. In vitro drug release rate and percent entrapment efficiency were determined for all formulations P1-P25 and found to be 95.306 ± 0.21 and 97.306 ± 0.65 in 12 h, respectively for best piperine-herbosome formulation (P2). It exemplifies the complex’s long-term releasing capability. This information suggests that it may have a longer retention time inside the body, extending the duration of effect. The antioxidant potential of pure piperine was determined using the DPPH scavenging method, with an IC50 value of 107.59 ± 0.11 g/mL compared to a formulation with an IC50 value of 93.926 ± 0.03 g/mL. Swiss albino mice of either sex were utilized for the evaluation of hepatoprotective activity. On the 8th day, the hepatotoxicity was caused by giving a single oral dosage of CCl4 (0.5 mL) and the parameters were evaluated on the 9th day. This formulation has the best optimized based on drug content and drug entrapment. Serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALP) and total bilirubin were among the biochemical markers measured. In comparison to normal control (161 ± 0.31 IU/L, 52.78 ± 0.28 IU/L, 121.12 ± 0.14 IU/L and 0.633 ± 1.44 IU/L) and P2 formulation (163.23 ± 0.49 IU/L, 66.9 ± 0.05 IU/L, 128.3 ± 1.15 IU/L and 0.645 ± 0.67 IU/L respectively).

OPTIMIZATION OF RIVASTIGMINE CHITOSAN NANOPARTICLES FOR NEURODEGENERATIVE ALZHEIMER; IN VITRO AND EX VIVO CHARACTERIZATIONS

Objective: In an attempt to optimize the anti-Alzheimer effect, rivastigmine-loaded chitosan nanoparticles were developed in order to target of brain through skin permeation. Methods: Rivastigmine-loaded chitosan-tripolyphosphate nanoparticles were prepared by modified ionic gelation method using tween 80 surfactants in different batches with variable chitosan/cross-linker ratios, desirability factors were applied to choose the optimal Nanocarrier and (F15) was selected. Different rivastigmine concentrations were loaded and the highest encapsulation efficiency formulae chosen for further study and evaluated by scanning electron microscopy (SEM), transmission electron microscopy (TEM) and differential scanning calorimetric (DSC). Further, drug loading, Ex-vivo skin permeation of Nano-gel, and kinetic studies were carried out in addition to stability along three months under different temperature. Results: Particle size and polydispersity index showed average 291.6±7.70 to 490.6±7.42 d. nm. and 0.333±0.04 to 0.570±0.023 respectively. The nanoparticles were spherical in shape. Drug concentrations 4% w/w showed the highest drug entrapment efficiency (89.80%) and drug loading (40.81). Ex vivo studies shows that gel formulae of rivastigmine loaded chitosan nanoparticles was not irritant to rat skin had better skin permeation than chitosan nanoparticles aqueous dispersion also capable of releasing the drug in a sustained manner, and follow kinetic diffusion model. Optimum formula F15 was physical and chemical stable. Conclusion: The experimental results showed the suitability of chitosan nanoparticles coated with a surfactant as a potential carrier for permeation through skin and brain, providing sustained delivery of rivastigmine.

FORMULATION AND DEVELOPMENT OF PRONIOSOMAL GEL FOR TOPICAL DELIVERY OF AMPHOTERICIN B

Objective: The present research work of Amphotericin B Proniosomal gel focuses on improving patient compliance by reducing the side effects of conventional intravenous injections and minimizing the problem of physical stability and to localize drug at site of action. Methods: Proniosomal gels are prepared by coacervation phase separation technique using different concentration of non-ionic surfactants (Span and Tween) for uniform vesicle formation, lecithin as permeation enhancer/membrane stabilizer and cholesterol as a vesicle cement providing prolonged release. Prepared gels were evaluated for their viscosity, pH, spreadability, entrapment efficiency, drug content uniformity, extrudability, in vitro drug release, permeability and stability studies. Results: Among the nine formulations, F2 (containing 10 mg drug, 250 mg Span 60, 50 mg Soya lecithin) was found to be promising. Fourier Transform infra-red (FT-IR) spectra studies represented no interaction and physicochemical characteristics were found within the limits. The percentages of drug content and entrapment efficiency were determined to be 95.16%±0.40 and 94.20%±0.20, respectively. In vitro drug release was about 95.72%±0.30. Conclusion: Proniosomal gel could constitute a promising approach for topical delivery of Amphotericin B by encapsulating it in non-ionic surfactant to provide patient compliance with cutaneous fungal infection, which was found to be safe, tolerable and efficacious.