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Optimization of Water/Oil/Surfactant System for Preparation of Medium-Chain-Length Poly-3-Hydroxyalkanoates (mcl-PHA)-Incorporated Nanoparticles via Nanoemulsion Templating Technique

Ishak KA, Annuar MSM, Ahmad N

Appl Biochem Biotechnol, 2017 Dec;183(4):1191-1208.
PMID: 28502064 DOI: 10.1007/s12010-017-2492-6

Polymeric nanoparticles gain a widespread interest in food and pharmaceutical industries as delivery systems that encapsulate, protect, and release lipophilic compounds such as omega-3 fatty acids, fat-soluble vitamins, carotenoids, carvedilol, cyclosporine, and ketoprofen. In this study, medium-chain-length poly-3-hydroxyalkanoate (mcl-PHA)-incorporated nanoparticle was developed via facile organic solvent-free nanoemulsion templating technique. The water content (W/surfactant-to-oil (S/O)), S/O, and Cremophor EL-to-Span 80 (Cremo/Sp80) ratios were first optimized using response surface methodology (RSM) to obtain nanoemulsion template prior to incorporation of mcl-PHA. Their effects on nanoemulsion formation were investigated. The mcl-PHA-incorporated nanoparticle system showed a good preservation capability of β-carotene and extended storage stability.

Matched MeSH terms: Hexoses/chemistry*
Fulltext Effect of surfactant and surfactant blends on pseudoternary phase diagram behavior of newly synthesized palm kernel oil esters

Mahdi ES, Sakeena MH, Abdulkarim MF, Abdullah GZ, Sattar MA, Noor AM

Drug Des Devel Ther, 2011;5:311-23.
PMID: 21792294 DOI: 10.2147/DDDT.S15698

The purpose of this study was to select appropriate surfactants or blends of surfactants to study the ternary phase diagram behavior of newly introduced palm kernel oil esters.

Matched MeSH terms: Hexoses/chemistry*
Fulltext Investigations on the generation of oil-in-water (O/W) nanoemulsions through the combination of ultrasound and microchannel

Manickam S, Sivakumar K, Pang CH

Ultrason Sonochem, 2020 Dec;69:105258.
PMID: 32702637 DOI: 10.1016/j.ultsonch.2020.105258

O/W nanoemulsions are isotropic colloidal systems constituted of oil droplets dispersed in continuous aqueous media and stabilised by surfactant molecules. Nanoemulsions hold applications in more widespread technological domains, more crucially in the pharmaceutical industry. Innovative nanoemulsion-based drug delivery system has been suggested as a powerful alternative strategy through the useful means of encapsulating, protecting, and delivering the poorly water-soluble bioactive components. Consequently, there is a need to generate an emulsion with small and consistent droplets. Diverse studies acknowledged that ultrasonic cavitation is a feasible and energy-efficient method in making pharmaceutical-grade nanoemulsions. This method offers more notable improvements in terms of stability with a lower Ostwald ripening rate. Meanwhile, a microstructured reactor, for instance, microchannel, has further been realised as an innovative technology that facilitates combinatorial approaches with the acceleration of reaction, analysis, and measurement. The recent breakthrough that has been achieved is the controlled generation of fine and monodispersed multiple emulsions through microstructured reactors. The small inner dimensions of microchannel display properties such as short diffusion paths and high specific interfacial areas, which increase the mass and heat transfer rates. Hence, the combination of ultrasonic cavitation with microstructures (microchannel) provides process intensification of creating a smaller monodispersed nanoemulsion system. This investigation is vital as it will then facilitate the creation of new nanoemulsion based drug delivery system continuously. Following this, the fabrication of microchannel and setup of its combination with ultrasound was conducted in the generation of O/W nanoemulsion, as well as optimisation to analyse the effect of varied operating parameters on the mean droplet diameter and dispersity of the nanoemulsion generated, besides monitoring the stability of the nanoemulsion. Scanning transmission electron microscopy (STEM) images were also carried out for the droplet size measurements. In short, the outcomes of this study are encouraging, which necessitates further investigations to be carried out to advance a better understanding of coupling microchannel with ultrasound to produce pharmaceutical-grade nanoemulsions.

Matched MeSH terms: Hexoses/chemistry
Alginate-based emulsion template containing high oil loading stabilized by nonionic surfactants

Ong WD, Tey BT, Quek SY, Tang SY, Chan ES

J Food Sci, 2015 Jan;80(1):E93-E100.
PMID: 25529579 DOI: 10.1111/1750-3841.12729

Oil-in-water (O/W) emulsion-gel systems containing high oil payloads are of increasing interest for food applications because of the reduction in encapsulation cost, consumption frequency or volume of food products. This study shows a facile approach to prepare stable alginate-based O/W emulsions at high oil loading using a mixture of nonionic surfactants (Tween 80 and Span 20) as a template to form gelled-emulsions. The synergistic effects of alginate and surfactants on the O/W emulsion properties were evaluated in terms of oil droplet size and emulsion stability. At 2% (w/v) of alginate and 1% (w/v) of surfactants, the size distribution of oil droplets was narrow and monomodal, even at an oil loading of 70% (v/v). The emulsions formed were stable against phase separation. The oil droplet size could be further reduced to below 1 μm using a high-shear homogenizer. The emulsions formed could be easily molded and gelled into solids of different shapes via ionic gelation. The findings of this study create possible avenues for applications in food industries.

Matched MeSH terms: Hexoses/chemistry
Excipient selection and aerodynamic characterization of nebulized lipid-based nanoemulsion loaded with docetaxel for lung cancer treatment

Asmawi AA, Salim N, Ngan CL, Ahmad H, Abdulmalek E, Masarudin MJ, et al.

Drug Deliv Transl Res, 2019 04;9(2):543-554.
PMID: 29691812 DOI: 10.1007/s13346-018-0526-4

Docetaxel has demonstrated extraordinary anticancer effects on lung cancer. However, lack of optimal bioavailability due to poor solubility and high toxicity at its therapeutic dose has hampered the clinical use of this anticancer drug. Development of nanoemulsion formulation along with biocompatible excipients aimed for pulmonary delivery is a potential strategy to deliver this poorly aqueous soluble drug with improved bioavailability and biocompatibility. In this work, screening and selection of pharmaceutically acceptable excipients at their minimal optimal concentration have been conducted. The selected nanoemulsion formulations were prepared using high-energy emulsification technique and subjected to physicochemical and aerodynamic characterizations. The formulated nanoemulsion had mean particle size and ζ-potential in the range of 90 to 110 nm and - 30 to - 40 mV respectively, indicating high colloidal stability. The pH, osmolality, and viscosity of the systems met the ideal requirement for pulmonary application. The DNE4 formulation exhibited slow drug release and excellent stability even under the influence of extreme environmental conditions. This was further confirmed by transmission electron microscopy as uniform spherical droplets in nanometer range were observed after storage at 45 ± 1 °C for 3 months indicating high thermal stability. The nebulized DNE4 exhibited desirable aerosolization properties for pulmonary delivery application and found to be more selective on human lung carcinoma cell (A549) than normal cell (MRC-5). Hence, these characteristics make the formulation a great candidate for the potential use as a carrier system for docetaxel in targeting lung cancer via pulmonary delivery.

Matched MeSH terms: Hexoses/chemistry
Transdermal delivery of oxybutynin chloride proniosomal gels for the treatment of overactive bladder

Rajabalaya R, David SR, Chellian J, Xin Yun G, Chakravarthi S

Drug Deliv, 2016 Jun;23(5):1578-87.
PMID: 26634274 DOI: 10.3109/10717544.2015.1116027

CONTEXT: Overactive bladder (OAB) is a common problem and anticholinergic drugs are first-line therapy, but they have side effects.
OBJECTIVE: Development of oxybutynin chloride (OC) proniosomal gels and analyses of its efficacy for OAB treatment.
MATERIALS AND METHODS: Phase separation coacervation was used to prepare proniosomal gels using various non-ionic surfactants, lipids, soy lecithin and isopropyl alcohol. Gels were characterized with regard to entrapment efficiency (EE), vesicle size, surface morphology (using environmental scanning electron microscopy [E-SEM]), stability, attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, in vitro skin permeation, in vivo animal studies and histopathology.
RESULTS AND DISCUSSION: EE was 87-92%, vesicle size was 0.38-5.0 μm, and morphology showed some loosened pores in proniosomes after hydration. ATR-FTIR spectroscopy showed no significant shifts in peaks corresponding to OC and excipients. Most formulations exhibited >50% permeation but the cholesterol-containing formulations P3 (Span 20:Span 60 [1:1]) and P4 [Tween 20:Tween 80 (1:1)] had the highest percent cumulative permeation. P3 and P4 also showed faster recovery of cholinergic effects on salivary glands than oral formulations. P3 and P4 had pronounced therapeutic effects in reduction of urinary frequency and demonstrated improvements in bladder morphology (highly regenerative surface of the transitional epithelium).
CONCLUSION: These results suggest that OC could be incorporated into proniosomal gels for transdermal delivery in the treatment of OAB.

Matched MeSH terms: Hexoses/chemistry*
Cellular uptake of Nigella sativa oil-PLGA microparticle by PC-12 cell line

Doolaanea AA, Mansor N', Mohd Nor NH, Mohamed F

J Microencapsul, 2014;31(6):600-8.
PMID: 24697178 DOI: 10.3109/02652048.2014.898709

The aim of this study is to investigate the cell uptake of Nigella sativa oil (NSO)-PLGA microparticle by neuron-like PC-12 cells in comparison to surfactants; hydrophilic (Tween 80 & Triton X100) and hydrophobic (Span 80). Solvent evaporation was used to precisely control the size, zeta potential and morphology of the particle. The results revealed varying efficiencies of the cell uptake by PC-12 cells, which may be partially attributed to the surface hydrophobicity of the microparticles. Interestingly, the uptake efficiency of PC-12 cells was higher with the more hydrophilic microparticle. NSO microparticle showed evidence of being preferably internalised by mitotic cells. Tween 80 microparticle showed the highest cell uptake efficiency with a concentration-dependent pattern suggesting its use as uptake enhancer for non-scavenging cells. In conclusion, PC-12 cells can take up NSO-PLGA microparticle which may have potential in the treatment of neurodegenerative disease.

Matched MeSH terms: Hexoses/chemistry
Fulltext Optimization of process parameters in preparation of tocotrienol-rich red palm oil-based nanoemulsion stabilized by Tween80-Span 80 using response surface methodology

Chong WT, Tan CP, Cheah YK, B Lajis AF, Habi Mat Dian NL, Kanagaratnam S, et al.

PLoS One, 2018;13(8):e0202771.
PMID: 30142164 DOI: 10.1371/journal.pone.0202771

Red palm oil (RPO) is a natural source of Vitamin E (70-80% tocotrienol). It is a potent natural antioxidant that can be used in skin-care products. Its antioxidant property protects skin from inflammation and aging. In our work, a tocotrienol-rich RPO-based nanoemulsion formulation was optimized using response surface methodology (RSM) and formulated using high pressure homogenizer. Effect of the concentration of three independent variables [surfactant (5-15 wt%), co-solvent (10-30 wt%) and homogenization pressure (500-700 bar)] toward two response variables (droplet size, polydispersity index) was studied using central composite design (CCD) coupled to RSM. RSM analysis showed that the experimental data could be fitted into a second-order polynomial model and the coefficients of multiple determination (R2) is 0.9115. The optimized formulation of RPO-based nanoemulsion consisted of 6.09 wt% mixed surfactant [Tween 80/Span 80 (63:37, wt)], 20 wt% glycerol as a co-solvent via homogenization pressure (500 bar). The optimized tocotrienol-rich RPO-based nanoemulsion response values for droplet size and polydispersity index were 119.49nm and 0.286, respectively. The actual values of the formulated nanoemulsion were in good agreement with the predicted values obtained from RSM, thus the optimized compositions have the potential to be used as a nanoemulsion for cosmetic formulations.

Matched MeSH terms: Hexoses/chemistry*
Development and in-vitro characterization of fish oil oleogels containing benzoyl peroxide and salicylic acid as keratolytic agents

Rehman K, Tan CM, Zulfakar MH

Drug Res (Stuttg), 2014 Mar;64(3):159-65.
PMID: 24026957 DOI: 10.1055/s-0033-1355351

Topical keratolytic agents such as benzoyl peroxide (BP) and salicylic acid (SA) are one of the common treatments for inflammatory skin diseases. However, the amount of drug delivery through the skin is limited due to the stratum corneum. The purposes of this study were to investigate the ability of fish oil to act as penetration enhancer for topical keratolytic agents and to determine the suitable gelator for formulating stable fish oil oleogels. 2 types of gelling agents, beeswax and sorbitan monostearate (Span 60), were used to formulate oleogels. To investigate the efficacy of fish oil oleogel permeation, commercial hydrogels of benzoyl peroxide (BP) and salicylic acid (SA) were used as control, and comparative analysis was performed using Franz diffusion cell. Stability of oleogels was determined by physical assessments at 20°C and 40°C storage. Benzoyl peroxide (BP) fish oil oleogels containing beeswax were considered as better formulations in terms of drug permeation and cumulative drug release. All the results were found to be statistically significant (p<0.05, ANOVA) and it was concluded that the beeswax-fish oil combination in oleogel can prove to be beneficial in terms of permeation across the skin and stability.

Matched MeSH terms: Hexoses/chemistry