Pharmaceutical Nanotechnology (v.4, #3)

Meet Our Associate Editor by Maria J. Blanco-Prieto (165-165).

EDITORIAL by Ijeoma Uchegbu (166-166).

Background: Rheumatoid arthritis (RA) is a debilitating disease which results in joint destruction, mainly due to chronic inflammation and oxidative stress. Meloxicam (MLX) is a preferential cyclooxygenase-2 (COX-2) inhibitor with potential free radical scavenging activity. Mixed nanomicelles (NMs) of MLX can augment its antioxidant effects.
Objective: The present study aims to prepare, characterize, and evaluate the in vitro antioxidant effects of MLX-loaded mixed nanomicelles (MLXNMs).
Method: Conventional thin-film hydration method was employed to fabricate MLX-NMs. The formulations were characterized for particle size, zeta potential, entrapment efficiency (EE), and drug loading (DL). Additionally, the optimized formulation was characterized for small-angle neutron scattering (SANS), in vitro drug release, and morphology. MLX encapsulation in NMs was confirmed by Fourier Transform Infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), 1H nuclear magnetic resonance (NMR), and X-ray diffraction (XRD), studies. The cell uptake of sulforhodamine B (SRB)- labeled NMs was studied in RAW 264.7 cells. The in vitro antioxidant activity of optimized MLX-NMs was studied by different antioxidant assays.
Results: The optimized MLX-NMs exhibited average size and zeta potential of 88 ± 42 nm and -47.4 ± 16.2 mV, respectively. The EE and DL of MLX were 94.13 ± 1.01 % and 4.20 ± 0.05 %, respectively. Morphology studies confirmed the oblate ellipsoidal shape of MLXNMs. The in vitro release study exhibited a biphasic release pattern. MLX encapsulation into the micelle core was confirmed by FTIR, DSC, 1H NMR, and XRD studies. Additionally, SRB-labeled NMs demonstrated efficient in vitro cell uptake in RAW 264.7 cells. Furthermore, in vitro antioxidant studies exhibited superior free radical scavenging activity of MLXNMs as compared to free MLX.
Conclusion: The NMs potentiate the in vitro antioxidant effects of MLX.

Fabrication & Characterization of 3D Electrospun Biodegradable Nanofibers for Wound Dressing, Drug Delivery and Other Tissue Engineering Applications by Oraib Abdallah, Fatemeh Jalali, Somayeh Zamani, Hesham M. Isamil, Shijimol Ma, Gheyath K. Nasrallah, Husam M. Younes (191-201).
Background: The use of electrospinning technology (ET) in fabrication of threedimensional biodegradable electrospun nanofibers scaffolds (BENS) has recently gained considerable attention in tissue engineering. BENS are superior to other existing scaffolds in tissue regeneration as they provide high surface area-to-volume ratio, possess high porosity, and offer a biomimetic environment in a nanometer scale.
Objectives: To fabricate & characterize BENS using Poly (ethylene glycol) (PEG35000) as a biodegradable polymer loaded with Amoxicillin Trihydrate (AMX) for use as a wound dressing.
Method: Solutions of PEG35000 in chloroform of varying concentrations were used to fabricate BENS using ET. Blank & 1% w/v AMX-loaded BENS were fabricated & characterized. Morphology of BENS were assessed using Scanning Electron Microscopy (SEM). Fourier Transform Infrared (FT-IR) Spectroscopy was used to identify the interaction between PEG35000 and AMX. Differential Scanning Calorimetry (DSC) was used to assess the crystallinity and thermal behavior of the prepared BENS. The X-Ray Diffraction (XRD) analysis for the blank and drug loaded electrospun fibers was carried out to identify the changes in their crystalline pattern. The in vitro antibacterial activity against common skin Gram-negative and Gram-positive pathogens was also tested.
Results: Blank & AMX loaded 35% w/v PEG35000 solutions produced the most homogenous and intact nanofibers. Major bands of AMX in FTIR were clearly observed in the spectrum of AMX with PEG35000 post electrospinning. Moreover, DSC thermograms indicated that AMX existed in its amorphous dispersed state within PEG fibers supported by the disappearance of its melting peak at 190°C and confirmed by the complete absence of AMX crystals under SEM. Finally, the results of DSC were confirmed by XRD patterns. Characterizing XRD peaks of AMX loaded with PEG3500 post electrospinning disappeared as an indication of the complete dispersion of AMX in the loaded fibers and its complete conversion to the amorphous form. The in vitro antibacterial assay confirmed the efficiency of the drug loaded fibers against the common skin pathogens.
Conclusion: BENS using PEG35000 loaded with AMX were successfully fabricated and characterized. Our findings show that PEG BENS has features that make it a promising candidate for wound healing applications.

Background and Objective: Nanoparticles have special properties, such as higher surface-to-volume ratio and higher reactivity, which increases cell penetrability and enhance their applicability in the field of medicine, especially in the case where other drugs are ineffective. Calcium phosphate nanoparticles (CPNP) and their encapsulation with therapeutic and/or diagnostic agents is such an agent synthesized. However, there are concerns related to the colloidal stability of these nanoparticles, which are reflected in their tendency to form aggregates in the physiological milieu. Therefore, successful translation of these nanoparticles from laboratory to the clinic requires studies of biodistribution and biocompatibility of nanoparticles for in vivo biomedical applications.
Method: Calcium phosphate nanoparticles synthesized and were tagged with a fluorophore and surface stabilized with trisilanol for stable aqueous dispersion. The in vivo biodistribution and sub-acute toxicological studies were done for orally-administered calcium phosphate nanoparticles.
Results: The biodistribution studies indicated that these nanoparticles were not prone to rapid degradation or excretion in the body, were long-circulating, and could appreciably permeate to the brain. Body/organ weight and biochemical analyses did not reveal much difference between nanoparticle-administered and saline-administered (control) groups. Finally, histopathological analyses of major organs such as liver, lungs, heart, stomach and kidney, did not reveal significant abnormalities in the treatment groups.
Conclusion: Thus, it is evident from these sub-acute toxicity studies that the nanoparticles appear to be non-toxic to rats following oral administration. These observations can have significant implications in calcium-phosphate nanoparticle-mediated non-toxic drug delivery to target organs, such as brain, via non-invasive, oral route.

Background: Tazarotene is used as topical retinoid for the treatment of acne, psoriasis and sun damaged skin. But its topical formulation has many side-effects including itching, burning, dryness, redness, stinging, rash blistering, skin discolouration, peeling at the site of application and low bioavailability.
Objective: The present study focuses on the reduction of side effects and enhancement of solubility and topical bioavailability of tazarotene by formulating nanosponge and niosomes based gel for topical application.
Methodology: Nanosponge and niosomes of tazarotene were prepared by emulsion solvent evaporation technique and thin film hydration method respectively. The prepared formulations were characterized for drug content, morphology, size distribution, PDI, viscosity, % swelling and in vitro permeation. The nanosponge and niosome formulations were incorporated into carbomer 940 (gel matrix) to convert them into nanosponge and niosome based gel. The gel formulations were subjected to drug content determination, pH determination, spreadability, viscosity, rheological behaviour and in vitro permeation studies using wistar rat skin by Franz diffusion cell for optimization. The optimized nanosponge (NSG1) containing ethyl cellulose, PVA and dichloromethane and optimized niosomes (NMG5) containing tween 20, cholesterol, chlororform were formulated into gels and compared with nanosponge (NS1), niosomes (NM5), plain drug gel and marketed formulation (Tazaorac) for skin permeation and retention characteristics.
Results: The nanosponge (NSG1) and niosome (NMG5) gel formulations had lower cumulative amount of drug permeated, flux, enhancement ratio and higher skin retention within the skin layers and local accumulation efficiency (LAE) than plain drug gel and marketed formulation.
Conclusion: Thus, the study showed that nanosponge and niosome based gel formulation can be a possible alternative to conventional formulations of tazarotene with enhanced bioavailability and skin retention characteristics for topical application.

Background: Flunarizine dihydrochloride is used as a prophylaxis to migraine. Flunarizine dihydrochloride nanoemulsion was fabricated in this research work. Since, it is a low soluble high permeable drug, work was designed to enhance the solubility and the same can be administered as nasal drug delivery for faster onset of action and therapeutic effect.
Objective: To fabricate a nanoemulsion of flunarizine dihydrochloride by using surfactant and co-surfactants.
Methods: The experimental work involved compatibility studies by using FTIR, crystallinity study by XRD. The prepared nanoemulsion was studied by photon correlation spectroscopy by master sizer 2000 for the particle size analysis and characterized for D10, D50 and D90 MPS, span and uniformity. Further studies were conducted by Laser light scattering technique by delsa nano common and TEM.
Results: The study demonstrated that the formulations (FNE 1 -FNE 5) demonstrated the MPS of 14, 22.7, 326.7, 14.3 and 40.73 respectively. The formulae FNE1 and FNE5 demonstrated the MPS of 214.6±179.9 and 2118.6 ±1503.6 with the diameter of 127.8 and 1307, respectively. The zeta potential of FNE1 was -3.84 mV and other parameters such as TEM and drug release studies were also reported.
Conclusion: The nanoemulsion of Flunarizine dihydrochloride was prepared successfully by using cremophor and labrafil which was better than the existed formula prepared by tween 80. The optimised formula demonstrated lower droplet size, satisfactory zeta potential, and high drug loading reproducible drug release profile.