Nanostructured Lipid Carriers Formulation Research Articles

Antitumor activity of essential oils-based nanostructured lipid carriers on prostate cancer cells

Prostate cancer (PCa) is the second most frequent malignancy in men worldwide. Essential oils (EOs) are natural products which can act in cancer suppression by several mechanisms. In this work, a nanotechnological approach was used to develop and evaluate the antineoplastic effects of EOs loaded by nanostructured lipid carriers (NLCs). Three different NLC systems composed of cinnamon, sage or thyme EOs were optimized using factorial design (23). The optimal formulations were characterized in terms of biophysical parameters, structure, stability, in vivo safety and efficacy. All optimized NLC formulations exhibited excellent structural properties and stability over a year (25 °C). They proved to be in vitro and in vivo biocompatible on PNT2 normal prostate cells and on chicken embryos (CE), respectively. In PC3 PCa cells, optimized NLCs inhibited cell proliferation and migration and changed its morphology. In CE xenograft tumor, NLCs have inhibited tumor growth and angiogenesis. The results from this work suggested that all developed EO-based NLC formulations had their stability improved while the biological activity remains unchanged.

The Incorporation of Clove Essential Oil into Nanostructured Lipid Carrier for Improvement of the Delivery and Antioxidant Effects on the Fibroblast Cells.

Clove (Syzygium aromaticum) essential oil (CO) has been studied extensively for its antioxidant properties but faces several limitations, including high volatility, low aqueous solubility, and irritation. We aimed to develop a Nanostructured Lipid Carrier (NLC) to enhance the benefits of CO. Using the emulsification sonication method, a liquid lipid component, surfactant concentration, and a co-surfactant were optimized to create CO-loaded NLC (CO-NLC). The developed CO-NLC was rigorously assessed for its stability during storage. Free radical scavenging activity and fibroblast oxidative stress protection were also measured to assess the antioxidant activity. The CO-NLC displayed a spherical shape with a hydrodynamic diameter of 125.77 ± 29.68 nm, homogenous particle distribution with polydispersity index of 0.26 ± 0.09, and a surface charge of -27.30 ± 4.56 mV with an encapsulation efficiency of 97% and a good stability profile. Furthermore, free CO and CO-NLC displayed very strong free radical scavenging activity with the IC50 value of 22.74 ± 0.57 µg/mL and 18.28 ± 2.63 µg/mL, respectively. However, only CO-NLC managed to protect fibroblast cells from the harmful effects of oxidative stress. The NLC formulations improved free radical scavenging activity and effectively protected fibroblasts from oxidative stress compared to free CO.

Optimizing Neuroprotective Nano-structured Lipid Carriers for Transdermal Delivery through Artificial Neural Network.

Dementia associated with Alzheimer's disease (AD) is a neurological disorder. AD is a progressive neurodegenerative condition that predominantly impacts the elderly population, although it can also manifest in younger people through the impairment of cognitive functions, such as memory, cognition, and behaviour. Donepezil HCl and Memantine HCl are encapsulated in Nanostructured Lipid Carriers (NLCs) to prolong systemic circulation and minimize the systemic side effects. This work explores the use of data mining tools to optimize the formulation of NLCs comprising of Donepezil HCl and Memantine HCl for transdermal drug delivery. Neuroprotective drugs and excipients are utilized for protecting the nervous system against damage or degeneration. The NLCs were formulated using a high-speed homogenization technique followed by ultrasonication. NLCs were optimized using Box Behnken Design (BBD) in Design Expert Software and artificial neural network (ANN) in IBM SPSS statistics. The independent variables included the ratio of solid lipid to liquid lipid, the percentage of surfactant, and the revolutions per minute (RPM) of the high-speed homogenizer. The NLCs that were formulated had a mean particle size ranging from 67.0±0.45 to 142.4±0.52nm. Both drugs have a %EE range over 75%, and Zeta potential was determined to be - 26±0.36mV. CryoSEM was used to do the structural study. The permeation study showed the prolonged release of the formulation. The results indicate that NLCs have the potential to be a carrier for transporting medications to deeper layers of the skin and reaching systemic circulation, making them a suitable formulation for the management of Dementia. Both ANN and BBD techniques are effective tools for systematically developing and optimizing NLC formulation.

Development of Nanostructured Lipid Carrier-Loaded Flavonoid-Enriched Zingiber officinale.

Flavonoids, which are bioactive molecules found in Zingiber officinale, have been widely used as antioxidant and anti-inflammatory drugs. The presence of nanostructured lipid carriers (NLCs) as sophisticated delivery systems for bioactive compounds, such as flavonoids, can increase their bioavailability and stability, thus potentially producing better therapeutic effects. This study aimed to develop an anti-inflammatory topical gel using NLC-containing flavonoids derived from Zingiber officinale. The NLC formulation was prepared using stearic acid, a mixture of medium-chain triglycerides and isopropyl myristate, Tween 20, and Span 20 by using a hot homogenization method. The total flavonoid content obtained through sequential maceration stages was 4.04 mg of QUE/g of dry extract. The highest encapsulation efficiency of flavonoid-loaded NLC was observed at a flavonoid, Zingiber officinale extract (ZOE) concentration of 2%. It was found that a ZOE concentration of 0.4% provided excellent stability with a particle size of 302-344 nm and a polydispersity index of 0.14-0.23 after 28 days of observation. Morphological analysis of the ZOE-loaded NLC revealed a stable and well-developed formulation with a fairly uniform distribution. The presence of distinctive and uniformly distributed single particles suggests a promising alternative drug delivery system for conventional topical preparations. ZOE-loaded NLC gel showed solid-like properties and higher quality stability than the gel.

Natural-Origin Betaine Surfactants as Promising Components for the Stabilization of Lipid Carriers.

In the present work, we demonstrate studies involving the influence of the formulation composition on the physicochemical properties of nanocarriers: solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs). Novel lipid-origin platforms were prepared using two "green" betaine-based surfactants, cocamidopropyl betaine (ROKAmina K30) and coco betaine (ROKAmina K30B), in combination with three different solid lipids, cetyl palmitate (CRODAMOL CP), trimyristin (Dynasan 114), and tristearin (Dynasan 118). Extensive optimization studies included the selection of the most appropriate lipid and surfactant concentration for effective SLN and NLC stabilization. The control parameters involving the hydrodynamic diameters of the obtained nanocarriers along with the size distribution (polydispersity index) were determined by dynamic light scattering (DLS), while shape and morphology were evaluated by atomic force microscopy (AFM) and transmission electron microscopy (TEM). Electrophoretic light scattering (ELS) and turbidimetric method (backscattering profiles) were used to assess colloidal stability. The studied results revealed that both betaine-stabilized SLN and NLC formulations containing CRODAMOL CP as lipid matrix are the most monodisperse and colloidally stable regardless of the other components and their concentrations used, indicating them as the most promising candidates for drug delivery nanosystems with a diverse range of potential uses.

An LC-MS/MS method development for dapagliflozinloaded nanostructured lipid carrier formulation in rabbit plasma

An LC-MS/MS method development for dapagliflozinloaded nanostructured lipid carrier formulation in rabbit plasma

Investigating the influence of lipids on Nano-structured lipid carrier formulation

The study aimed to evaluate the effect of different lipids on the properties of nanostructured lipid carrier (NLC) formulations. The particle size, zeta potential, polydispersity index, entrapment efficiency, and drug release at 24 hours were analyzed for formulations containing various lipid matrices. Among the formulations tested, N3 (Compritol 888 ATO and Softigen) exhibited the most favourable characteristics, including the smallest particle size, highest entrapment efficiency, sustained drug release, and good stability, as indicated by a high zeta potential. Other lipids, such as Witepsol H 32 and Beeswax, also showed desirable properties. The formulations containing Dynasan 114 and Acconon-C-44 EP/NF resulted in larger particle sizes, lower entrapment efficiencies, and slower drug release. Cholesterol exhibited distinct properties, with a lower zeta potential and moderate drug release. The findings highlight the importance of lipid selection in determining the performance and functionality of NLC formulations. Compritol 888 ATO and Softigen were identified as suitable lipids for further optimization of NLC formulations. These lipids contribute to the formation of stable and uniform NLC particles, which are desirable for efficient drug delivery systems. The study provides valuable insights for formulating NLCs with optimized characteristics, facilitating the development of effective drug delivery systems. Future research can focus on optimizing other factors to enhance the performance and therapeutic effectiveness of NLC formulations.

Box-Behnken Design for Formulation, Characterization and In-vivo Antidiabetic Activity of Pioglitazone Loaded Nanostructured Lipid Carriers

This study employs a 23 full factorial design in the design of experiment (DOE) technique to assess the impact of critical quality attributes (CQAs) on critical process parameters (CPPs) in the formulation of pioglitazone (PGZ) loaded nanostructured lipid carriers (NLCs). The three chosen CPPs are the quantity of liquid lipid (Captex 300), the proportion of solid lipid (Glyceryl Palmitostearate), and the amount of surfactant. The CQAs evaluated are entrapment efficiency (%EE) and particle size. The PGZ-loaded NLCs are prepared through a solvent injection method. The lipid phase, consisting of dissolved medication and lipids in ethanol, is rapidly injected into an aqueous phase containing the surfactant. The resulting dispersion undergoes analysis for entrapment effectiveness and particle size. Additionally, the in-vivo antidiabetic activity of the optimal formulation is examined using diabetic rat models induced by streptozotocin (STZ), and relevant biochemical parameters are assessed. The results demonstrate that the proposed PGZ-loaded NLCs exhibit superior antidiabetic activity and favorable physicochemical characteristics compared to free PGZ. This study provides valuable insights into the formulation and characterization of NLCs for enhanced diabetes management, emphasizing their potential as a promising delivery system to improve the therapeutic efficacy of antidiabetic drugs like PGZ

Improved Transdermal Delivery of Anti-hypertensive Drug Loaded Nanostructured Lipid Carriers: Statistical Design, Optimization, Depiction and Pharmacokinetic Assessment

Background: The vasoselective calcium-channel blocker lercanidipine hydrochloride (LCH) is poorly absorbed orally (only 10% bioavailability) owing to its low solubility and hepatic metabolism. Because of the LCH's poor solubility and permeability, bioavailability is low and very variable, stable aqueous liquid formulations are challenging to create, and a uniform distribution of the medication is almost impossible to produce. Objective: The purpose of this research was to see whether an approach involving the development of nanostructured lipid carriers (NLCs) might be used to create an effective, innovative oral formulation of LCH. The efficacy of several synthetic and natural liquid lipids was compared using a hot homogenization-ultrasonication strategy. Methods: Following initial improvements with hot homogenization and ultrasonication, the LCHloaded NLCs formulation was fine-tuned by Box-Behnken statistical analysis. The optimal LCHNLCs composition includes the lipid phase (2-4% w/v) of stearic acid and oleic acid, the surfactants poloxamer 188 (1%) and Tween 80(1%), and other ingredients. Results: The optimized NLCs formulation was found to have mean vesicle sizes of 128.72±1.59 nm, polydispersity indices of 0.169±0.06, zeta potentials of -36.81±0.42 mV, and entrapment efficiencies of 79.84±0.11%. The optimized NLCs formulation released much more LCH (88.74±4.62) than the LCH-suspension (36.84±0.37%) in in-vitro drug release experiments lasting up to 24 hours. Ex vivo studies on the ability of LCH-NLCs to pass through the gut showed that drug permeation was much better than it was with plain LCH-solution. The in vivo pharmacodynamic analysis demonstrated that, compared to conventional LCH-suspension, NLCs released LCH more slowly and steadily over a longer time period. Conclusion: These findings provide additional evidence that NLCs have great promise as a drug delivery technology for the treatment of hypertension, just as they show promise as a controlled release formulation for the treatment of LCH.

Nanostructured Lipid Carriers for Improved Delivery of Therapeutics via the Oral Route

Drug delivery via the oral route has always been challenging for poorly soluble drugs. Acid-induced hydrolysis, enzymatic degradation, and poor mucosal absorbency remain the primary hiccups for effective oral delivery of medications. With the advent of nanotechnology, nanostructured lipid carriers (NLCs) have emerged as a promising delivery carrier that can circumvent gastrointestinal tract (GIT) barriers hindering the solubility and bioavailability of such drugs. These NLCs can efficiently transport drug moieties across intestinal membranes shielding medications from intestinal pH and enzymatic degradation. Because they are composed of lipidic materials, they can be easily absorbed or taken up by various pathways such as transcellular absorption, paracellular transport, and M-cell uptake. Such mechanisms not only improve the absorption and solubility of drugs but also augment bioavailability and residence time and may bypass first-pass metabolism. This review explores the diverse applications of nanostructured lipid carriers (NLCs) in oral drug delivery for various medical conditions, shedding light on their current regulatory status, including FDA-approved options and those in pre/clinical stages. The review also features patented NLC formulations. It provides valuable insights into how NLCs can be harnessed for effective oral drug delivery and outlines recent advancements in optimizing their performance to tackle gastrointestinal barriers, thus opening new possibilities for NLCs in future pharmaceutical applications.

Encapsulation of vitamin D3 using rhamnolipids-based nanostructured lipid carriers.

This work had as main objective to encapsulate vitamin D3 (VD3) into nanostructured lipid carriers (NLCs) using rhamnolipids as surfactant. Glycerol monostearate and medium chain triglycerides with 2.625 % of VD3 were used as lipid materials. The three formulations of NLCs with VD3 (NLCs+VD3) were composed by 99 % of aqueous phase, 1 % of lipid phase and 0.05 % of surfactant. The difference between them was the ratio of solid:liquid in lipid phase. The NLCs+VD3 sizes ranged between 92.1 and 108.1nm. The most stable formulation maintaining their caracteristics for 60days at 4°C. The NLCs+VD3 cytotoxicity demonstrated that concentrations of 0.25mg/mL or lower up had a good biocompatibility in vitro. During the in vitro digestion, formulations with lower sizes and higher content on solid lipid had higher lipolysis rate and consequently higher VD3 bioaccessibility. The rhamnolipids-based NLCs are a good option for the encapsulation of VD3.

The Gelatin-Coated Nanostructured Lipid Carrier (NLC) Containing Salvia officinalis Extract: Optimization by Combined D-Optimal Design and Its Application to Improve the Quality Parameters of Beef Burger.

The current study aims to synthesize the gelatin-coated nanostructured lipid carrier (NLC) to encapsulate sage extract and use this nanoparticle to increase the quality parameters of beef burger samples. NLCs were prepared by formulation of gelatin (as surfactant and coating biopolymer), tallow oil (as solid lipid), rosemary essential oil (as liquid lipid), sage extract (as active material or encapsulant), polyglycerol ester and Tween 80 (as low-molecular emulsifier) through the high-shear homogenization-sonication method. The effects of gelatin concentrations and the solid/liquid ratio on the particle size, polydispersity index (PDI), and encapsulation efficiency (EE%) of sage extract-loaded NLCs were quantitatively investigated and optimized using a combined D-optimal design. Design expert software suggested the optimum formulation with a gelatin concentration of 0.1 g/g suspension and solid/liquid lipid ratio of 60/40 with a particle size of 100.4 nm, PDI of 0.36, and EE% 80%. The morphology, interactions, thermal properties, and crystallinity of obtained NLC formulations were investigated by TEM, FTIR, DSC, and XRD techniques. The optimum sage extract-loaded/gelatin-coated NLC showed significantly higher antioxidant activity than free extract after 30 days of storage. It also indicated a higher inhibitory effect against E. coli and P. aeruginosa than free form in MIC and MBC tests. The optimum sage extract-loaded/gelatin-coated NLC, more than free extract, increased the oxidation stability of the treated beef burger samples during 90 days of storage at 4 and -18 °C (verified by thiobarbituric acid and peroxide values tests). Incorporation of the optimum NLC to beef burgers also effectively decreased total counts of mesophilic bacteria, psychotropic bacteria, S. aureus, coliform, E. coli, molds, and yeasts of treated beef burger samples during 0, 3, and 7 days of storage in comparison to the control sample. These results suggested that the obtained sage extract-loaded NLC can be an effective preservative to extend the shelf life of beef burgers.

Development of NLC-based Sunscreen Gel of Green Tea Extract and Its In-vitro Characterization

Background: Green tea extract is a hydrophilic antioxidant. The challenge associated with its cutaneous administration is its poor penetration. A system of solid-liquid lipids formulated in the form of a nanostructured lipid carrier (NLC), can improve the penetration. In addition, Vitamin E oil used as a liquid lipid will aid in skin hydration, reduce particle size, and enhance penetration. Objective: The objective of this study was to formulate the NLC-based sunscreen gel of green tea extract. Methods: Nanostructured lipid carriers (NLC) were prepared by melt emulsion ultrafiltration technique and were evaluated for particle size, zeta potential, polydispersity index (PDI), drug loading (DL), encapsulation efficacy (EE), and in vitro drug release. The optimised formula was incorporated into a suitable gel base and an in-vitro sun protection factor (SPF) was determined. Beeswax and Vitamin E oil were chosen as solid and liquid lipids for NLC formulation. Results: The particle size, PDI, zeta potential, entrapment efficiency, and in vitro drug release of optimised formulation (NLC4) were found to be 139.4 nm, 0.236, -11.0 mV, 84.20%, and 85% respectively. The SPF value of green tea extract-NLC-loaded gel was found to be 20.035. Conclusion: The result of the current investigation depicted that lipid nanoparticles are suitable carriers for green tea extract to be delivered as sunscreen gel.

Natural-based edible nanocomposite coating for beef meat packaging

Researchers have made significant discoveries in addressing the limitations of essential oils (EOs) in food packaging using encapsulation systems combined with nanoparticles (NPs). This study aimed to develop a unique coating for beef preservation using nanostructured lipid carriers (NLCs). The optimal formulation of NLCs was determined based on size, zeta potential, and loading rate, achieving a content of 71.4% savory EO. A composite coating containing NPs was then created using different concentrations of NLCs (0, 0.85%, 1.7%, 2.55%, and 3.4%). The antimicrobial effectiveness of the coatings was assessed using well-diffusion assays to identify the best coating (17 mm). This optimized coating was applied to beef samples for 12 days, and extensive evaluation was conducted over time. The results demonstrated that the encapsulation percentage was higher than 98.7%. The optimal coating (CMC-OM-ZnO NPs-NLCs 3.4%) significantly reduced microbial growth (total count: over 1.6 log CFU/g), pH, thiobarbituric acid value (TBA), and total volatile nitrogen (TVN) compared with the control samples (P < 0.05). Overall, this novel bioactive packaging enriched with lipidic and inorganic nanomaterials represents an innovative way to improve meat products' oxidative and microbial stability.

Anti-leishmaniasis effect of nano-structured lipid carrier containing glucantime drug: Preparation, characterization, in-vitro and in-vivo evaluation

The aim of this study was to prepare a nano-structured lipid carrier (NLC) containing Meglumine Antimoniate (MA) for treatment of leishmaniasis. Haftyzer-Van Krevelen mathematical modeling was applied to select the best components for preparing nanoparticles with smaller particle size, higher drug encapsulation efficiency, and more stability over time. Mathematical results were approved by the experimental study. Then, ex-vivo and in-vivo antileishmanial performance of the NLC formulation was investigated on the healthy and leishmania major BALB/C female mice, respectively. Characterization results showed that the optimal NLC formulation had a mean particle size of 93 ± 0.1 nm with uniform particle size distribution and proper zeta potential about −30 ± 0.25 mV. Drug entrapment efficiency was 74 ± 0.37%. In-vitro drug release studies at pH = 7.4 showed a controlled drug release from NLC formulation in comparison to commercial ampule. Ex-vivo analysis results approved the highest reduction of the promastigotes number and proper penetration of drug from the skin layers of the healthy BALB/C female mice for NLC sample. In-vivo results showed that new NLC formulation created a significant reduction in leishmaniasis wound size with reducing the number of parasites in comparison to the commercial ampule. Furthermore, lower inflammation, redness, depth and stiffness was observed for NLC formulation group. Hematological analysis results confirmed that unlike the commercial formulation, the new formulation significantly reduced systemic drug absorption and drug side effects, including variance of liver enzymes and blood factors. In conclusion, NLC formulation was proposed as a safe alternative for delivering glucantime in injection administration route compared with commercial ampule.

Quercetin and Morin dual drug loaded nanostructured lipid carriers: formulation and in vitro cytotoxicity study on MCF7 breast cancer cells

The aim of the study was to prepare nanostructured lipid carriers (NLCs) co-encapsulated with Quercetin and Morin and to compare the cytotoxicity of the NLCs with individual drugs as well as with their combination form. The Quercetin and Morin co-encapsulated NLCs were prepared by ultrasonication method. The size of the NLCs particles, the zeta potential value, % of drug entrapment efficiency (% EE), and % of cumulative drug release (% CDR) were estimated. The in vitro cytotoxicity study was carried out in MCF 7 cancer cell. The size of the NLCs particles ranged from 297.6 ± 14.1 to 456.4 ± 14.1 nm. The % EE of Quercetin and Morin in the optimized NLCs formulation (F6) were found to be 84.27 ± 2.1% and 87.11 ± 2.6%, respectively. However, the % CDR of Morin and Quercetin from the F6 formulation were 72.11 ± 3.4% and 81.56 ± 3.6%, respectively. The results of FTIR spectroscopy study indicated that the functional groups of Quercetin and Morin were remained intact in NLCs formulations. The TEM study result revealed that the prepared NLCs were spherical in shape. The in vitro cytotoxicity study result revealed that dual drug loaded NLCs showed higher cytotoxicity as compared to individual drug and their combinations. It was concluded that the Quercetin and Morin co-encapsulated NLCs formulation could be a promising candidate for combating the chemotherapy resistance in breast cancer.

Nanostructured Lipid Carriers Enriched Hydrogels for Skin Topical Administration of Quercetin and Omega-3 Fatty Acid.

Chronic skin exposure to external hostile agents (e.g., UV radiation, microorganisms, and oxidizing chemicals) may increase oxidative stress, causing skin damage and aging. Because of their well-known skincare and protective benefits, quercetin (Q) and omega-3 fatty acids (ω3) have attracted the attention of the dermocosmetic and pharmaceutical sectors. However, both bioactives have inherent properties that limit their efficient skin delivery. Therefore, nanostructured lipid carriers (NLCs) and enriched PFC® hydrogels (HGs) have been developed as a dual-approach vehicle for Q and/or ω3 skin topical administration to improve bioactives' stability and skin permeation. Two NLC formulations were prepared with the same lipid composition but differing in surfactant composition (NLC1-soy lecithin and poloxamer 407; NLC2-Tween® 80 and dioctyl sodium sulfosuccinate (DOSS)), which have an impact on physicochemical properties and pharmaceutical and therapeutic performance. Despite both NLCs presenting high Q loading capacity, NLC2's physicochemical properties make them more suitable for topical skin administration and ensure longer colloidal stability. Additionally, NLC2 demonstrated a more sustained Q release, indicating higher bioactive storage while improving permeability. The occlusive effect of NLCs-enriched HGs also has a positive impact on skin permeability. Q-loaded NLC2, with or without ω3, -enriched HGs demonstrated efficacy as antioxidant and photoprotective formulations as well as effective reduction in S. aureus growth, indicating that they constitute a promising approach for topical skin administration to prevent skin aging and other damaging cutaneous processes.

Enhanced Codelivery of Gefitinib and Azacitidine for Treatment of Metastatic-Resistant Lung Cancer Using Biodegradable Lipid Nanoparticles.

Lung cancer is a formidable challenge in clinical practice owing to its metastatic nature and resistance to conventional treatments. The codelivery of anticancer agents offers a potential solution to overcome resistance and minimize systemic toxicity. The encapsulation of these agents within nanostructured lipid carriers (NLCs) provides a promising strategy to enhance lymphatic delivery and reduce the risk of relapse. This study aimed to develop an NLC formulation loaded with Gefitinib and Azacitidine (GEF-AZT-NLC) for the treatment of metastatic-resistant lung cancer. The physicochemical properties of the formulations were characterized, and in vitro drug release was evaluated using the dialysis bag method. The cytotoxic activity of the GEF-AZT-NLC formulations was assessed on a lung cancer cell line, and hemocompatibility was evaluated using suspended red blood cells. The prepared formulations exhibited nanoscale size (235-272 nm) and negative zeta potential values (-15 to -31 mV). In vitro study revealed that the GEF-AZT-NLC formulation retained more than 20% and 60% of GEF and AZT, respectively, at the end of the experiment. Hemocompatibility study demonstrated the safety of the formulation for therapeutic use, while cytotoxicity studies suggested that the encapsulation of both anticancer agents within NLCs could be advantageous in treating resistant cancer cells. In conclusion, the GEF-AZT-NLC formulation developed in this study holds promise as a potential therapeutic tool for treating metastatic-resistant lung cancer.

Topical caffeine-loaded nanostructured lipid carriers for enhanced treatment of cellulite: A 32 full factorial design optimization and in vivo evaluation in rats

The goal of this study was the development and evaluation of semisolid caffeine (CAF) loaded nanostructured lipid carriers (NLCs) for topical treatment of cellulite. CAF-loaded NLC formulations were prepared via high-speed homogenization followed by ultrasonication. A 32 full factorial design was employed for formulation optimization. The total lipid content (%) and the liquid lipid content per total lipids (%) were chosen as factors, whereas particle size (PS), polydispersity index (PDI), zeta potential (|ZP|) and viscosity (VIS) were selected as responses. The design suggested CAF-NLC3 as the optimum formulation consisting of a total lipid content of 15% w/w (palmitic acid and soft paraffin/isopropyl myristate, 7:3 w/w) and a surfactant content of 10% w/w (Tween 80/lecithin, 8:1.2 w/w). CAF-NLC3 revealed PS, PDI, ZP, VIS and CAF content values of 318.8 nm, 0.253, −41.1 mV, 18.0 Pa.s and 97.57%, respectively. It showed a pseudoplastic rheological behavior, acceptable pH value (5.25), good spreadability (1.12 mm2/g) and spherical shape employing transmission electron microscopy. Differential scanning calorimetry and X-ray diffraction demonstrated the amorphization of CAF in CAF-NLC3. CAF-NLC3 remained stable for 3 months at room and refrigeration conditions. A single topical application of CAF-NLC3 on shaved abdominal skins of Wistar rats revealed enhanced skin retention of CAF by 2-fold and 1.4-fold after 4 h when compared with plain CAF gel (CAF-P) and marketed CAF gel (CAF-M), respectively. Furthermore, CAF-NLC3 exhibited a superior anti-cellulite activity in comparison with CAF-P and CAF-M through elevating extracellular matrix components (collagen 1, elastin and hyaluronic acid) and stimulating the brown adipose tissue thermogenesis via up-regulating UCP1 and PPAR-γ expression. In addition, CAF-NLC3 prominently increased lipolysis through HSL activity and decreased pro-inflammatory cytokines such as ICAM-1 and VCAM-1 after 30 days of treatment on a high fat diet-induced cellulite rat model. These findings were further confirmed by histopathological examination supported by morphometric analysis. Therefore, incorporation of CAF in a semisolid NLC formulation would be a promising cosmetic approach for the topical treatment of cellulite.

Scale Up Nanostructured Lipid Carrier (NLC) Koenzim Q10 Menggunakan Matriks Lipid Asam Stearat-Isopropil Palmitat

Overexposure to the sun can lead to the production of reactive oxygen species (ROS), which accelerates the aging process of the skin. The formation of ROS can be prevented with antioxidant compounds. Coenzyme Q10 is a lipophilic antioxidant because it has 10 isoprene side chains, causing coenzyme Q10 to have low skin penetration ability. Thus, the Coenzyme Q10 Nanostructured Lipid Carrier (NLC) technology was created to improve coenzyme Q10's skin penetration. This research examined the physicochemical properties of scaled-up Coenzyme Q10 NLC formulation. The method used is High Shear Homogenization HSH), by testing two formulas, namely F1 with 20% surfactant content and 30% surfactant F2. The results obtained for the physicochemical characteristics of F1 and F2 were seen from the organoleptic parameters which were yellowish in color, semisolid, and had a characteristic odor of fat; viscosity (825.60±537.63cps; 2588.33±584.42cps), pseudoplastic flow properties; pH (5,74±0,057; 5,80±0,021), particle size (592,33±158,19nm; 257,5±39,53nm), zeta potential (-12,73±18.5mV; -36, 1±20.91mV), polydispersity index (0,461±0,129; 0,223±0,104), spherical and smooth surface morphology; decreased and increased peak height at º2Th (21.5645, 23.005; 18.9246, 22.9967), and no interaction was found between the active ingredient and the carrier. This study finds that a successful formulation of coenzyme Q10 NLC has been made.&#x0D;