Pharmaceutical Nanotechnology - Volume 6, Issue 3, 2018

In the last decades, nanoparticles intended for biomedical applications have gained increased attention due to the advantages they represent among the current diagnostic and therapeutic methods. However, the translation of nanomaterials laboratory results to human therapies is limited, mainly due to incomplete characterization of nanosystem properties, before preclinical studies. In this context, this review aims to summarize the main physicochemical characterization techniques of nanoparticles in a liquid dispersion, required in their design steps; which is of utmost importance for successful applications. One of the key physicochemical parameters of nanomaterials is size. To assess nanoparticles' size, a wide revision of light scattering and microscopic techniques is reported here, some of them being also useful for determining nanomaterial morphology. The determination of nanosystem surface charge is also reported, because it is also a key parameter that will influence their interaction with biological components. In addition, the determination of nanomaterials' stability, which is important in terms of storage and use, is described. In conclusion, this review will be a useful support to find the appropriate techniques for an appropriate nanoparticle physicochemical preclinical characterization.

Objective: To assess the biofilm inhibition activity of biosynthesized silver nanoparticles (AgNPs) using Curcuma longa. Method: Characterizations of these biogenic nanoparticles were done by UV-Vis spectroscopy, TEM, EDX and nanoparticles tracking analyzer. The antibiofilm activity of AgNPs against S. aureus and S. pneumoniae was carried out by 96 well plate method. Further, the combined effect of AgNPs with the antibiotic was studied against S. aureus and S. pneumoniae. Results: UV-spectroscopic analysis showed a surface plasmon resonance peak at 415nm. The shape of AgNPs is spherical with an average size of 20-40 nm while the elemental silver was confirmed by EDX analysis. These biosynthesized AgNPs have anti-biofilm activity against S. aureus and S. pneumoniae. Furthermore, the combined effect of AgNPs with an antibiotic, showed enhanced anti-biofilm activity against both the strains under study. Conclusion: C. longa mediated AgNPs showed potent anti-biofilm activity.

Background: Transdermal drug delivery is an attractive approach for both local and systemic therapeutics of various diseases. Transdermal drug delivery systems show various advantages like reduction of local irritation, prevention of first-pass hepatic metabolism, and bioavailability enhancement of bioactive molecules over conventional drug delivery systems. Objective: The main objective of the present research work was to develop and characterize (in-vitro and ex-vivo) econazole nitrate loaded transethosomes and their comparison with marketed cream of econazole nitrate [Ecoderm, Brown and Burk Pharmaceutical (Pvt.) Ltd., Bengaluru, India] for effective transdermal delivery. Method: Transethosomes loaded with econazole nitrate were developed by homogenization method and evaluated for entrapment (%), vesicular size, zeta potential, polydispersity index (PDI), and invitro drug release. Furthermore, optimized econazole nitrate loaded transethosomes were added to Carbopol 934 gel and this gel was evaluated for viscosity, pH, drug content, ex-vivo skin permeation and retention studies followed by in-vitro antifungal activity against C. albicans fungus. Results: The optimized transethosomes loaded with econazole nitrate showed vesicle size of 159.3 ± 4.3 nm, entrapment efficiency about 78.3 ± 2.8%, acceptable colloidal properties like (zeta potential = -27.13 ± 0.33 mV, PDI = 0.244 ± 0.045), approximately 57.56 ± 2.33% drug release up to 24 h. Results of DSC analysis confirmed the encapsulation of econazole nitrate inside transethosomes. Optimized transethosomes showed drug release following zero order through diffusion mechanism. Transethosomal gel showed high drug content (92.35 ± 0.63%) and acceptable values of pH (5.68 ± 0.86) or viscosity (10390 ± 111 cPs). Transethosomal gel showed less ex-vivo skin penetration (17.53 ± 1.20%), high ex-vivo skin retention (38.75 ± 2.88%), and high in-vitro antifungal activity compared to the marketed cream of econazole nitrate. Conclusion: Therefore, it can be concluded that econazole nitrate loaded transethosomes are effective to deliver econazole nitrate transdermally in a controlled fashion for effective elimination of cutaneous candidiasis.

Objective: To prepare chitosan-okra gum nanoparticles and their evaluation as mucoadhesive drug delivery system for intranasal delivery of esculin. Method: Esculin loaded chitosan-okra gum based nanoparticles were prepared using ionic gelation method. The preparation method was optimized using Box-Behnken experimental design employing okra gum concentration, chitosan concentration, pH and stirring speed as independent variables and particle size, encapsulation efficiency and zeta potential of the formulation were selected as dependent variables. The optimized formulation was characterized using FTIR, SEM and TEM. The nanoparticles were evaluated for their bioadhesive strength and in vitro drug release studies. The optimized intranasal formulation was administered to rats and the pharmacokinetic profile and biodistribution studies were carried out to calculate the targeting efficiency of the formulation in the brain. Results: The nanoparticles were found to depict particle size in the range of 294.0 to 613.4 nm. The concentration of gums was found to significantly influence the particle size and encapsulation efficiency. The nanoparticles depicted bioadhesive strength of 32±2%. The in vitro drug release studies showed 96.4±4.2% release of esculin from nanoparticles in 4h. The drug targeting of NPs to brain was found to be nearly double that of esculin given as simple solution. Conclusion: The nanoparticles prepared using chitosan-okra gum were found to possess good mucoadhesive strength with and high brain targeting efficiency.

Background: The progression of fungal infections can be rapid and serious due to compromising with immune function. They may cause liver damage, affect estrogen levels or may cause allergic reactions. Oxiconazole nitrate (OXZN) is a broad spectrum commonly used antifungal drug. It acts by erogosterol biosynthesis inhibition, which causes lysis of the fungal cell membrane because of changes in both membrane integrity and fluidity and direct membrane damage of fungal cells. However, its poor water solubility and short half-life (3-5 h) limit its applications. Objective: This study aimed to develop and evaluate OXZN-loaded nanostructured lipid carrier (NLC) to improve its solubility and prolong its release for the treatment of fungal infection via topical administration. Method: OXZN-NLC was prepared by ultrasonication method using 32 full factorial design. Glyceryl monostearate (GMS) (X1) and oleic acid (X2) were used as independent variables and particle size and percentage entrapment efficiency (% EE) as dependent variables. The OXZN-NLCs were characterized for particle size, particle morphology and entrapment efficiency. Results: The mean diameter of optimized OXZN-NLCs was found to be 124 ± 2 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM). Skin deposition study showed about 82.74% deposition as compared with the marketed formulation that showed 68.42% deposition. The developed NLCs show a sustained release pattern and high drug disposition in the infected area. Conclusion: OXZN-NLC could be a potential alternative for the treatment of topical fungal infection after clinical evaluation in near future.

Background: Facile, environmental friendly synthesis of metal oxide nanoparticles is of paramount importance when its biological applications are considered. Objective: Current study reports phyto-fabrication of Zinc oxide nanoparticles using aqueous extract of Piper betel leaves as stabilizing and capping agent using co-precipitation method. Results: P betel synthesized ZnO nanoparticles (PZnO) was characterized using Powder X-ray diffraction, UV-Visible spectroscopy, scanning electron microscopy and dynamic light scattering. PXRD pattern demonstrated hexagonal wurtzite structure with preferred orientation (100) plane confirmed by JCPDS file 36-1451. UV- Vis spectroscopy showed peak at 370 nm due to band edge of semiconductor, the PZnO. The average particle size determined by DLS measurement was 69 nm and morphologically the particles were short rod shaped and agglomerated as demonstrated by SEM images. Antibacterial activity of PZnO against dental pathogens namely Streptococcus mutans and Lactobacillus acidphillus was performed using well-diffusion method and antioxidant activity against 2, 2 diphenyl 1 picrylhydrazyl (DPPH) free radicals and were compared with ZnO used in clinical dentistry (DZnO). PZnO showed higher antioxidant activity of ~70% at 200 μg/mL with consistent activity at lower aliquots. PZnO showed higher antimicrobial activity than DZnO against both tested microbes and also exhibited inhibitory effects in concentration as low as 3.25 μg/mL. Cytotoxicity study using Balb 3T3 mouse fibroblast cell lines showed <40% cellular growth inhibition by both PZnO and DZnO, indicating their benignity towards selected cell lines. Conclusion: Phyto-fabricated facile PZnO nanoparticles having demonstrable antibacterial and antioxidant activity can be considered for use in clinical dentistry after further clinical trials.

Background: Tuberculosis (TB) is one of the major health challenge in the world. The current treatment of TB needs daily administration of combined drug therapy for six or more months. Sometime non-adherence and less bioavailability from current therapy develops multidrug resistance, as a result, high dose requirement and subsequent intolerable toxicity are seen. Therefore, nanotechnology gained special attention as it has potential to improve patient compliance, bioavailability and reduction in dosing frequency. Objective: The aim of this study is to fabricate alginate-chitosan nanoparticles (AL-CS NPs) under appropriate conditions using ionic gelation method. The use of natural polymers in nanoparticle fabrication has a vast application due to their biodegradability, biocompatibility and nontoxic nature. Ionic gelation method involves the interaction between macromolecules with opposite charged ionizable groups forming polyelectrolyte complex. Hence, it is rational to formulate natural polymerbased sustained release nano-particulate matrix to improve patient adherence, reducing dose frequency and drug toxicity. Method: The formulations were based on 32 factorial designs. Nanoparticles of combined drug (Isoniazid- INH and Pyrazinamide-PYZ) were fabricated using natural polymer. Formulation process involved the use of pregelated sodium alginate followed by ionic gelation with chitosan. Pregelation of sodium alginate included calcium chloride. The effects of sodium alginate concentration and chitosan concentration on particle size, zeta potential, entrapment efficiency and in vitro drug release were studied. Results: Optimized Batch-3s showed particle size 539.7 ± 2.33 nm, zeta potential -26.4 ± 0.55 mV, and entrapment efficiency is 70.21 ± 0.24% and 73.45 ± 0.21% of INH and PYZ, respectively. Dissolution release study of Batch-3s in 7.4 pH phosphate buffer exhibited the initial burst of 5.04 ±0.45% and 19.68 ± 0.87% at 0.25 hrs followed by slow, sustained release of drug 74.53 ± 2.53 and 57.87 ± 2.04% at 10 hrs of INH and PYZ, respectively. Conclusion: It concluded that chitosan (CS) and sodium alginate (AL) concentration are rate-limiting factors in formulation development. Natural polymer based combined drug nano-particulate system could be an innovative and optimistic approach in the treatment of TB.