Hot-melt Emulsification Research Articles

Formulation, Development & Evaluation of Mallotus philippensis Extract Loaded NLCS based Nanogel for Psoriasi.

The current study’s objective was to develop and evaluate the potential of Bergenin-loaded nanostructured lipid carriers (NLCs) as a novel topical therapeutic for psoriasis, obtained from Mallotus philippensis. NLCs loaded with Bergenin were created using a modified Hot-melt emulsification technique, and then Box-Behnken design optimization was performed. The Independent factors were concentration of solid lipid, the concentration of liquid lipid and the concentration of surfactant. Particle size, entrapment efficiency, and drug permeation percentage were the dependent variables. The Bergenin-nano-lipid carriers (NLCs) that has been optimized has a Particle size of 148 ± 0.37 nm, an %Entrapment efficiency of 93.44 ± 0.45%, and a drug permeation percentage was found to be 83.56 ± 0.137. and the zeta potential was - 0.0617 ± 5.53 mV and the polydispersity index (PDI) was 0.30 ± 0.03. Bergenin’s existence within the NLCs was verified by FTIR. The outcomes show that Nanostructured lipid carriers have the ability to deliver Bergenin for topical psoriasis treatment.

CBD-Loaded Nanostructured Lipid Carriers: Optimization, Characterization, and Stability.

Cannabidiol (CBD) has demonstrated its potential to enhance depression treatment through various biological pathways. However, the application potential of CBD is significantly impeded by its polymorphic nature, limited water solubility, and hepatic first-pass metabolism. To improve chemical stability and water solubility, nanostructured lipid carriers loaded with CBD (CBD-NLCs) were developed using a hot-melt emulsification method and optimized by response surface methodology (RSM). The process parameters were optimized using a four-factor and three-level Box-Behnken experimental design consisting of 29 experiments. The CBD-NLCs were formulated and characterized, demonstrating desirable properties, including a mean particle size of 54.33 nm, a PDI value of 0.118, a zeta potential of -29.7 mV, and an impressive encapsulation efficiency rate of 87.58%. The nanoparticles were found to possess an approximately spherical shape, as revealed by scanning and transmission electron microscopy. The stability studies have demonstrated that CBD-NLCs effectively mitigated the photodegradation of CBD and exhibited a stable behavior for 42 days when stored. The CBD-NLCs displayed a biphasic release profile characterized by an initial burst release (over 50% of CBD released within 20 min) followed by a subsequent gradual and sustained release, aligned with first-order kinetics and Fickian diffusion. These findings demonstrate the potential suitability of this formulation as a carrier for CBD in food fortification and pharmaceutical applications.

Myristic Acid Solid Lipid Nanoparticles Enhance the Oral Bioavailability and Therapeutic Efficacy of Rifaximin against MRSA Pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption. Solid lipid nanoparticles have good biocompatibility, high drug loading, sustained release performance, and the inertia of lipids in gastric acid, which facilitates oral drug delivery. In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs). This study first prepared RFX-SLNs through hot melt emulsification and ultrasonic methods and selected the optimal formula of RFX-SLNs through single-factor screening. Afterward, the particle size, zeta potential, and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high-performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model. The optimal formulation of RFX-SLNs was 1% RFX with water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical in shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. This indicates that RFX-SLNs can be used for the oral treatment of bacterial infections. Compared to RFX, RFX-SLNs showed good therapeutic effects in a mouse MRSA pneumonia infection model. This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs. This not only opens up avenues for the clinical application of RFX but also provides a way for the development of new dosage forms of water-soluble drugs and the expansion of their clinical application scope.

Rational design of solid lipid-polymer hybrid nanoparticles: An innovative glycoalkaloids-carrier with potential for topical melanoma treatment

Despite the promising potential of Solanum plant glycoalkaloids in combating skin cancer, their clinical trials have been halted due to dose-dependent toxicity and poor water solubility. In this study, we present a rational approach to address these limitations and ensure colloidal stability of the nanoformulation over time by designing solid lipid-polymer hybrid nanoparticles (SLPH). Leveraging the biocompatible and cationic properties of polyaspartamides, we employed a new polyaspartamide derivative (P1) as a raw material for this class of nanostructures. Subsequently, we prepared SLPH through a one-step process involving hot-melt emulsification followed by ultrasonication. The physicochemical properties of the SLPH were thoroughly characterized using dynamic light scattering (DLS), ζ-potential analysis, nanoparticle tracking analysis (NTA), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM). The optimized formulation exhibited long-term stability over six months under low temperatures, maintaining a particle size around 200 nm, a polydispersity index (PdI) lower than 0.2, and a ζ-potential between +35–40 mV. Furthermore, we evaluated the cytotoxic effect of the SLPH against human cutaneous melanoma cells (SK-MEL-28) compared to human foreskin fibroblast cells (HFF-1). Encapsulation of glycoalkaloids into the nanoparticles (SLPH-GE) resulted in a two-fold greater selective cytotoxic profile for melanoma cells than glycoalkaloids-free (GE). The nanoparticles disrupted the stratum corneum barrier with a penetration depth of approximately 77 μm. These findings underscore the potential of the developed nanosystem as an effective glycoalkaloid carrier with suitable colloidal and biological properties for further studies in topical treatment strategies for cutaneous melanoma.

Determination of Chlorogenic Acid in Solid-lipid Nanoparticles: Validation by UV-spectroscopy

Objective: The objective of the research was the development and validation of a simple, sensitive, accurate, robust, and precise UV-spectroscopic method for the quantitative determination of chlorogenic acid loaded in solid-lipid nanoparticles as per the guidelines of the International Conference on Harmonization. Methods: The solid-lipid nanoparticles of chlorogenic acid were prepared using the hot melt emulsification method and the high-speed homogenizer method. Glyceryl monostearate was used as a solid lipid, and Tween 80 was used as a surfactant for the preparation of chlorogenic acid-loaded solid lipid nanoparticles. The method was validated in terms of linearity, accuracy, precision, robustness, ruggedness, limit of detection, and limit of quantification. Results: The chlorogenic acid exhibited absorption maxima at the wavelength of 330 nm. The regression equation from the calibration curve was y=0.006x + 0.0193 with a correlation coefficient of 0.9989. The percentage recovery was found to be 99.92, 99.80, and 99.86, respectively (within the acceptable limit of 98-102%), which validated the accuracy of the method. Furthermore, the method exhibited precision, robustness, and ruggedness, as illustrated by a relative standard deviation (RSD) of less than 2%. The limit of detection and limit of quantification were found to be 6.97 and 21.13 μg/ml, respectively. Conclusion: It was concluded that the proposed spectrophotometer analytical method for the determination of Chlorogenic acid was found reliable, accurate, consistent, precise, accurate, and robust. Therefore, the proposed analytical technique could be an integral part of further evaluation and characterization of Chlorogenic acid-solid lipid nanoparticles.

Antiproliferative activity of syringic acid-loaded nanostructured lipid carriers against MCF-7 human breast carcinoma cells

Syringic acid (SA) is a phenolic herbal compound known to exert antiproliferative properties. However, its poor aqueous solubility and low bioavailability lead to limited therapeutic efficacy in treating breast cancer. Hence, to overcome the above problems, the current study aims to explore the quality by design (QbD) optimized syringic acid loaded nanostructured lipid carriers (SA-NLCs) to treat breast cancer. Here, SA-NLCs were formulated via the hot-melt emulsification method and optimized using the Box-Behnken design. The SA-NLCs exhibited spherical shapes with a particle size and zeta potential of 142.7 ± 4 nm and −14.5 ± 3.6 mV, respectively. The differential scanning calorimetry and powder XRD analyses showed the conversion of crystalline to amorphous form of SA after entrapping into NLCs. Also, the optimized SA-NLCs showed sustained drug release of 75.5 % and 97.6 % in pH 5.5 acetate buffer solution and pH 7.4 phosphate buffer saline respectively. The drug release kinetics study revealed that the optimized SA-NLCs exhibit the Weibull model with the Fickian drug release mechanism. Further, a significantly improved cytotoxicity of the optimized SA-NLCs (IC50: 3.8 ± 0.2 μg/mL) was observed as compared to free SA (IC50: 14.5 ± 1.2 μg/mL) on MCF-7 human breast carcinoma cell lines. Thus, the improved cytotoxicity of SA-NLCs on MCF-7 cell lines can be a suitable strategy for breast cancer treatment.

Design Optimization and Evaluation of Solid Lipid Nanoparticles of Azelnidipine for the treatment of Hypertension.

Solid lipid nanoparticles (SLN) are the most promising lipid-based drug delivery utilized for enhancing the solubility, bioavailability, and therapeutic efficacy of poorly water-soluble molecules. Azelnidipine (AZN) is a calcium channel blocker widely recommended for the treatment of high blood pressure but its activity is restricted due to high lipophilicity and poor solubility in the GIT. The current research focused on the development of the SLN of AZN and thereby improving the absorption, bioavailability, and therapeutic efficacy in hypertension which is a leading cause of death worldwide. Recent patents on SLN was available as U.S. Patent,10,973,798B2, U.S. Patent 10,251,960B2, U.S. Patent 2021/0069121A1, U.S. Patent 2022/0151945A1. SLN was developed by hot melt emulsification and ultrasonication method using glyceryl monostearate (GMS) as solid lipid and Poloxamer 188 as a surfactant for the stabilization of colloidal dispersion. Box-Behnken model was utilized which predicted 13 batches in which concentration of GMS (X1), Poloxamer 188 (X2) and sonication time (X3) were considered as independent parameters. The particle size (Y1) and entrapment efficiency (Y2) were dependable parameters and optimized batch F2 showed a particle size of 166.4 nm, polydispersity index of 0.40 and zeta potential of -13.7 mV. The entrapment efficiency was observed at 86.21 %. FTIR spectra confirm the identity and compatibility with the formulation components. The differential scanning calorimetry (DSC) confirmed the absence of melting point and interpreted that AZN was entirely incorporated in the lipid matrix and transformed from crystalline to amorphous form. The ANOVA for the particle size (p-value: 0.0203), % EE (p-value: 0.0271) was found significant. The in-vitro drug release showed a sustained release pattern for about 12 h. The AZN-loaded SLN was lyophilized and intended for oral delivery. AZN-loaded SLN was developed by the hot melt emulsification method which accelerated the solubility and bioavailability and released in a sustained manner for treating hypertension.

Repaglinide-Solid Lipid Nanoparticles in Chitosan Patches for Transdermal Application: Box-Behnken Design, Characterization, and In Vivo Evaluation.

Repaglinide (REP) is an antidiabetic drug with limited oral bioavailability attributable to its low solubility and considerable first-pass hepatic breakdown. This study aimed to develop a biodegradable chitosan-based system loaded with REP-solid lipid nanoparticles (REP-SLNs) for controlled release and bioavailability enhancement via transdermal delivery. REP-SLNs were fabricated by ultrasonic hot-melt emulsification. A Box-Behnken design (BBD) was employed to explore and optimize the impacts of processing variables (lipid content, surfactant concentration, and sonication amplitude) on particle size (PS), and entrapment efficiency (EE). The optimized REP-SLN formulation was then incorporated within a chitosan solution to develop a transdermal delivery system (REP-SLN-TDDS) and evaluated for physicochemical properties, drug release, and ex vivo permeation profiles. Pharmacokinetic and pharmacodynamic characteristics were assessed using experimental rats. The optimized REP-SLNs had a PS of 249±9.8 nm and EE of 78%±2.3%. The developed REP-SLN-TDDS demonstrated acceptable characteristics without significant aggregation of REP-SLNs throughout the casting and drying processes. The REP-SLN-TDDS exhibited a biphasic release pattern, where around 36% of the drug load was released during the first 2 h, then the drug release was sustained at around 80% at 24 h. The computed flux across rat skin for the REP-SLN-TDDS was 2.481±0.22 μg/cm2/h in comparison to 0.696±0.07 μg/cm2/h for the unprocessed REP, with an enhancement ratio of 3.56. The REP-SLN-TDDS was capable of sustaining greater REP plasma levels over a 24 h period (p<0.05). The REP-SLN-TDDS also reduced blood glucose levels compared to unprocessed REP and commercial tablets (p<0.05) in experimental rats. Our REP-SLN-TDDS can be considered an efficient therapeutic option for REP administration.

Formulation Development and Evaluation of Dry Adsorbed Nanoparticles of Curcumin and Piperine Dual Drug Loaded Nanostructured Lipid Carriers

Purpose: The present study was aimed at preparing stable dry adsorbed nanoparticles (DANs) of curcumin (CUR) and piperine (PIP) loaded nanostructured lipid carriers (NLCs). Methods: CUR and PIP-loaded NLCs (CP NLCs) were prepared by modified hot-melt emulsification using precirol ATO5 (PRE) as solid lipid, labrafac lipophile WL1349 (LAF) as liquid lipid, and a combination of tween 80 (T80) with gelucire 50/13 (G50/13) as surfactants. The NLCs system was subjected to physical stability, particle size, zeta potential, thermal behaviour, crystallinity study and in-vitro drug release. Further, an evaporative drying technique converted the NLC system into stable DANs by adsorbing onto mannitol (Pearlitol 200SD). The DANs were characterized for redispersion properties, particle size, flow properties and in-vitro drug release. The stability studies were carried out for 30 days. Results: The optimized CP NLCs were of imperfect type and had a mean particle size of 248.5 ± 12.8 nm (size distribution of 0.216 ± 0.021), a zeta potential of -9.03 ± 0.53 mV, an entrapment efficiency (EE) of 99.80 ± 0.21% (CUR), 100.05 ± 0.07% (PIP) with a drug recovery of 99.70 ± 0.21% (CUR) and 100.36 ± 0.12% (PIP). The X-ray diffraction pattern and endothermic peaks confirmed the encapsulation of actives in lipid matrices. The in-vitro drug release showed controlled release for 24 h. The optimized DANs led to maximum redispersion and retained a particle size of 268.4 ± 23.1 nm (distribution 0.235 ± 0.037) with controlled release similar to CP NLCs. The CP NLCs DANs showed reasonable stability for 30 days. Conclusions: The developed CP NLCs DANs showed a controlled release profile, and the adsorption technique can be used to improve the stability of NLC dispersion. The DANs can be offered in patient-friendly dosage forms such as sachets, capsules, and compressed tablets.

Exploring temozolomide encapsulated PEGylated liposomes and lyotropic liquid crystals for effective treatment of glioblastoma: in-vitro, cell line, and pharmacokinetic studies

Temozolomide (TMZ) is one of the best choices for treating glioblastoma. However, due to the short plasma half-life, only 20–30 % brain bioavailability can be achieved using traditional formulations. In the present study, PEGylated liposomes and lyotropic liquid crystals (LLCs) were developed and investigated to prolong the plasma circulation time of TMZ. Industrially feasible membrane extrusion and modified hot melt emulsification techniques were utilized during the formulation. Liposomes and LLCs in the particle size range of 80–120 nm were obtained with up to 50 % entrapment efficiency. The nanocarriers were found to show a prolonged release of up to 72 h. The cytotoxicity studies in glioblastoma cell lines revealed a ∼1.6-fold increased cytotoxicity compared to free TMZ. PEGylated liposomes and PEGylated LLCs were found to show a 3.47 and 3.18-fold less cell uptake in macrophage cell lines than uncoated liposomes and LLCs, respectively. A 1.25 and 2-fold increase in the plasma t1/2 was observed with PEGylated liposomes and PEGylated LLCs, respectively, compared to the TMZ when administered intravenously. Extending plasma circulation time of TMZ led to significant increase in brain bioavailability. Overall, the observed improved pharmacokinetics and biodistribution of TMZ revealed the potential of these PEGylated nanocarriers in the efficient treatment of glioblastoma.

Lyophilized Nasal Inserts of Atomoxetine HCl Solid Lipid Nanoparticles for Brain Targeting as a Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): A Pharmacokinetics Study on Rats.

The study aims to investigate the ability of lyophilized nasal inserts of nanosized atomoxetine HCl solid lipid nanoparticles (ATM-SLNs) to transport atomoxetine (ATM) directly to the brain and overcome the first-pass metabolism. In this case, 16 formulae of (ATM-SLNs) were prepared using hot melt emulsification, stirring and ultrasonication method technique. A full factorial design was established with 24 trials by optimization of four variables; lipid type (Compritol 888 ATO or stearic acid) (X1), lipid to drug ratio [(1:2) or (2:1)] (X2), span 60: Pluronic f127 ratio [(1:3) or (3:1)] (X3) and probe sonication time (five or ten minutes) (X4). The prepared SLNs were characterized for entrapment efficiency (EE%), in-vitro drug release after 30 min (Q30min), particle size (PS), zeta potential (ZP) and polydispersity index (PDI). Design Expert® software was used to select the optimum two formulae. The morphological examination for the optimum two formulae was carried out using a transmission electron microscope (TEM). Furthermore, eight lyophilized nasal inserts were prepared by using a 23 full factorial design by optimization of three variables: type of (ATM-SLNs) formula (X1), type of polymer (NOVEON AA1 or HPMC K100m) (X2) and concentration of polymer (X3). They were evaluated for nasal inserts' physicochemical properties. The two optimum inserts were selected by Design Expert® software. The two optimum insets with the highest desirability values were (S4 and S8). They were subjected to DSC thermal stability study and in-vivo study on rats. They were compared with atomoxetine oral solution, atomoxetine (3 mg/kg, intraperitoneal injection) and the pure atomoxetine solution loaded in lyophilized insert. (ATM-SLNs) showed EE% range of (41.14 mg ± 1.8% to 90.6 mg ± 2.8%), (Q30min%) of (27.11 ± 5.9% to 91.08 ± 0.15%), ZP of (-8.52 ± 0.75 to -28.4 ± 0.212% mV), PS of (320.9 ± 110.81% nm to 936.7 ± 229.6% nm) and PDI of (0.222 ± 0.132% to 0.658 ± 0.03%). Additionally, the two optimum (ATM-SLNs) formulae chosen, i.e., F7 and F9 showed spherical morphology. Nasal inserts had assay of drug content of (82.5 ± 2.5% to 103.94 ± 3.94%), Q15min% of (89.9 ± 6.4% to 100%) and Muco-adhesion strength of (3510.5 ± 140.21 to 9319.5 ± 39.425). DSC results of S4 and S8 showed compatibility of (ATM) with the other excipients. S8 and S4 also showed higher trans-nasal permeation to the brain with brain targeting efficiency of (211.3% and 177.42%, respectively) and drug transport percentages of (52.7% and 43.64%, respectively). To conclude, lyophilized nasal inserts of (ATM-SLNs) enhanced (ATM) trans-nasal drug targeting permeation and brain targeting efficiency.

Nanostructured lipid carrier-loaded metformin hydrochloride: Design, optimization, characterization, assessment of cytotoxicity and ROS evaluation

Metformin hydrochloride (MET) is commonly used in diabetes treatment. Recently, it has gained interest for its anticancer potential against a wide range of cancers. Owing to its hydrophilic nature, the delivery and clinical actions of MET are limited. Therefore, the present work aims to develop MET-encapsulated NLCs using the hot-melt emulsification and probe-sonication method. The optimization was accomplished by 33 BB design wherein lipid ratio, surfactant concentration, and sonication time were independent variables while the PS (nm), PDI, and EE (%) were dependent variables. The PS, PDI, % EE and ZP of optimized GMSMET-NLCs were found to be 114.9 ± 1.32 nm, 0.268 ± 0.04 %, 60.10 ± 2.23 %, and ZP − 15.76 mV, respectively. The morphological features, DSC and PXRD, and FTIR analyses suggested the confirmation of formation of the NLCs. Besides, optimized GMSMET-NLCs showed up to 88 % MET release in 24 h. Moreover, GMSMET-NLCs showed significant cell cytotoxicity against KB oral cancer cells compared with MET solution as shown by the reduction of IC50 values. Additionally, GMSMET-NLCs displayed significantly increased intracellular ROS levels suggesting the GMSMET-NLCs induced cell death in KB cells. GMSMET-NLCs can therefore be explored to deliver MET through different routes of administration for the effective treatment of oral cancer.

Preparation, Characterization and Pharmacokinetics of Tolfenamic Acid-Loaded Solid Lipid Nanoparticles.

The clinical use of nonsteroidal anti-inflammatory drugs is limited by their poor water solubility, unstable absorption, and low bioavailability. Solid lipid nanoparticles (SLNs) exhibit high biocompatibility and the ability to improve the bioavailability of drugs with low water solubility. Therefore, in this study, a tolfenamic acid solid lipid nanoparticle (TA-SLN) suspension was prepared by a hot melt–emulsification ultrasonication method to improve the sustained release and bioavailability of TA. The encapsulation efficiency (EE), loading capacity (LC), particle size, polydispersity index (PDI), and zeta potential of the TA-SLN suspension were 82.50 ± 0.63%, 25.13 ± 0.28%, 492 ± 6.51 nm, 0.309 ± 0.02 and −21.7 ± 0.51 mV, respectively. The TA-SLN suspension was characterized by dynamic light scattering (DLS), fluorescence microscopy (FM), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared (FT-IR) spectroscopy. The TA-SLN suspension showed improved sustained drug release in vitro compared with the commercially available TA injection. After intramuscular administration to pigs (4 mg/kg), the TA-SLN suspension displayed increases in the pharmacokinetic parameters Tmax, T1/2, and MRT0–∞ by 4.39-, 3.78-, and 3.78-fold, respectively, compared with TA injection, and showed a relative bioavailability of 185.33%. Thus, this prepared solid lipid nanosuspension is a promising new formulation.

Fabrication of nanostructured lipid carriers ocugel for enhancing Loratadine used in treatment of COVID-19 related symptoms: statistical optimization, in-vitro, ex-vivo, and in-vivo studies evaluation

Loratadine (LORA), is a topical antihistamine utilized in the treatment of ocular symptoms of COVID-19. The study aimed to develop a Loratadine Nanostructured Lipid Carriers Ocugel (LORA-NLCs Ocugel), enhance its solubility, trans-corneal penetrability, and bioavailability. full-factorial design was established with 24 trials to investigate the impact of several variables upon NLCs properties. LORA-NLCs were fabricated by using hot melt emulsification combined with high-speed stirring and ultrasonication methods. All obtained formulae were assessed in terms of percent of entrapment efficiency (EE%), size of the particle (PS), zeta potential (ZP), as well as in-vitro release. Via using Design Expert® software the optimum formula was selected, characterized using FTIR, Raman spectroscopy, and stability studies. Gel-based of optimized LORA-NLCs was prepared using 4% HPMC k100m which was further evaluated in terms of physicochemical properties, Ex-vivo, and In-vivo studies. The optimized LORA-NLCs, comprising Compritol 888 ATO®, Labrasol®, and Span® 60 showed EE% of 95.78 ± 0.67%, PS of 156.11 ± 0.54 nm, ZP of −40.10 ± 0.55 Mv, and Qh6% of 99.67 ± 1.09%, respectively. Additionally, it illustrated a spherical morphology and compatibility of LORA with other excipients. Consequently, gel-based on optimized LORA-NLCs showed pH (7.11 ± 0.52), drug content (98.62%± 1.31%), viscosity 2736 cp, and Q12% (90.49 ± 1.32%). LORA-NLCs and LORA-NLCs Ocugel exhibited higher ex-vivo trans-corneal penetrability compared with the aqueous drug dispersion. Confocal laser scanning showed valuable penetration of fluoro-labeled optimized formula and LORA-NLCs Ocugel through corneal. The optimized formula was subjected to an ocular irritation test (Draize Test) that showed the absence of any signs of inflammation in rabbits, and histological analysis showed no effect or damage to rabbit eyeballs. Cmax and the AUC0–24 were higher in LORA-NLCs Ocugel compared with pure Lora dispersion-loaded gel The research findings confirmed that NLCs could enhance solubility, trans-corneal penetrability, and the bioavailability of LORA.

Compritol-Based Nanostrucutured Lipid Carriers (NLCs) for Augmentation of Zolmitriptan Bioavailability via the Transdermal Route: In Vitro Optimization, Ex Vivo Permeation, In Vivo Pharmacokinetic Study.

Migraine is a severe neurovascular disease manifested mainly as unilateral throbbing headaches. Triptans are agonists for serotonin receptors. Zolmitriptan (ZMP) is a biopharmaceutics classification system (BCS) class III medication with an absolute oral bioavailability of less than 40%. As a result, our research intended to increase ZMP bioavailability by developing transdermal nanostructured lipid carriers (NLCs). NLCs were prepared utilizing a combination of hot melt emulsification and high-speed stirring in a 32 full factorial design. The studied variables were liquid lipid type (X1) and surfactant type (X2). The developed NLCs were evaluated in terms of particle size (Y1, nm), polydispersity index (Y2, PDI), zeta potential (Y3, mV), entrapment efficacy (Y4, %) and amount released after 6 h (Q6h, Y5, %). At 1% Mygliol as liquid lipid component and 1% Span 20 as surfactant, the optimized formula (NLC9) showed a minimum particle size (138 ± 7.07 nm), minimum polydispersity index (0.39 ± 0.001), acceptable zeta potential (−22.1 ± 0.80), maximum entrapment efficiency (73 ± 0.10%) and maximum amount released after 6 h (83.22 ± 0.10%). The optimized formula was then incorporated into gel preparation (HPMC) to improve the system stability and ease of application. Then, the pharmacokinetic study was conducted on rabbits in a cross-over design. The calculated parameters showed a higher area under the curve (AUC0–24, AUC0–∞ (ng·h/mL)) of the developed ZMP-NLCs loaded gel, with a 1.76-fold increase in bioavailability in comparison to the orally administered marketed product (Zomig®). A histopathological examination revealed the safety of the developed nanoparticles. The declared results highlight the potential of utilizing the proposed NLCs for the transdermal delivery of ZMP to improve the drug bioavailability.

Potential of transpapillary route for artesunate-loaded microneedles against breast cancer cell line

Breast cancer is the most common cancer in women with highest mortality rate wherein, mastectomy, lumpectomy, radiation therapy, hormone therapy, chemotherapy, and biological therapy are some of the current therapeutic alternatives for breast cancer. The treatments, however, are linked to short and long-term side effects like cardiac problems, anemia, physiological distress, myelosuppression, peripheral neuropathy and thrombosis. Hence, the transpapillary route is a promising route for delivering drugs directly to the underlying breast tissues for the treatment of breast cancer by achieving higher drug levels at the tumor site. The aim of the present study was to check the potential of transpapillary route for artesunate-loaded microneedles, solid lipid nanoparticles (SLN)-loaded microneedles and layer-by-layer (LBL)-coated SLN-loaded microneedles against breast cancer. SLNs were prepared by hot-melt emulsification method and LBL-coating on SLNs was achieved by 1 mg/1 mL of chitosan and 2 mg/mL of hyaluronic acid. The particle sizes of selected formulations of SLNs and LBL-coated SLNs were found to be 213.72 ± 2.53 nm and 319.39 ± 1.25 nm, respectively. Zeta potentials of selected formulations SLNs and LBL-coated SLNs were found to be −27.32 ± 4.45 mV and −28.41 ± 3.67 mV, respectively. Three formulations of microneedles were prepared for comparative evaluation using artesunate, SLNs, LBL-coated SLNs. Microneedles were evaluated for FTIR, DSC, mechanical insertion property, surface morphology, in-vitro release, ex-vivo release and cell line studies. The cell line study and ex-vivo release profile of LBL-coated SLN microneedles showed a reduction in growth of cell line MCF 7 by 7.92 ± 1.54% and higher ex-vivo release (84.75 ± 2.02%) in comparison to plain drug. Thus, the LBL-coated SLNs microneedles of artesunate proved as an effective alternative against breast cancer cell line.

Solid nanostructured lipid carriers loaded with silymarin for oral delivery: Formulation development and evaluation

The present study was aimed at preparing stable dry adsorbed nanoparticles (DANs) of silymarin loaded nanostructured lipid carriers (NLCs). The prepared silymarin loaded NLCs and DANs were characterized for various quality parameters. Silymarin loaded NLCs were prepared by a modified hot melt emulsification ultra-sonication method using glyceryl monostearate (GMS), capmul MCM C8 EP (CAP) and gelucire 50/13 (G50/13) as solid lipid, liquid lipid and surfactant respectively. For better stability, NLC dispersion was converted into DANs by adsorbing them onto some suitable carriers. NLCs and DANs were characterized for particle size, polydispersity index, zeta potential, entrapment efficiency, drug loading, assay, thermal behavior, crystallinity and morphological study. The optimized NLCs have a mean particle size of 206.1±012.5 nm (size distribution of 0.249±0.058), a zeta potential of -32.5±1.2 mV with high entrapment of 95.60±0.45% and drug loading of 1.90±0.08%. The X-ray diffraction and endothermic peaks confirmed the maximum encapsulation of active in lipid matrices. The particles were spherical with smooth surface morphology. In-vitro release studies showed sustained drug release for up to 24 h. Ex-vivo permeation in the presence and absence of lymphatic blocker indicates the uptake of silymarin loaded NLCs by the lymphatic route. Silymarin loaded NLCs prepared had a nanosize distribution with high entrapment efficiency. The ex-vivo permeation study for optimized NLC formulation exhibited the lymphatic uptake of active. Dispersion stability was increased by preparing the DANs. The solid dry powder is used for oral reconstitution and can be further converted into tablets or filled into capsules.

Fabrication and evaluation of Lambda-Cyhalothrin nanosuspoemulsion with pH- and temperature-responsive based on polyethylene wax as carrier

Using polyethylene wax (PW) as the coating matrix, the lambda-cyhalothrin-PW nanosuspoemulsion (LC-PW) with a particle size of 80-150nm was prepared through high-speed stirring, hot melt emulsification and ultrasonic dispersion. The formulation and composition of the LC-PW were optimized, the morphology of the LC-PW was analyzed by dynamic light scattering (DLS) and TEM, and the structure of the LC-PW was characterized by UV and IR. The anti-photolysis test showed that LC-PW had a good anti-photolysis performance. Furthermore, LC-PW could sustainably release Lambda-cyhalothrin, which was pH- and temperature dependent. The insecticidal activity analysis in the greenhouse indicated that the toxic strength between LC-PW and LC-SC (lambda-cyhalothrin-suspension concentrate) to Mythimna separata was similar within the same concentration ranges tested, but the insecticidal duration of LC-PW was significantly longer than LC-SC. Thus, the new type of LC-PW with the properties of anti-photolysis and controlled release is suitable for application in the field as a better insecticide.

Nose to brain delivery of Rotigotine loaded solid lipid nanoparticles: Quality by design based optimization and characterization

Rotigotine (RTG), for the treatment of Parkinson disease has low oral bioavailability (1–5%) due to its high gut clearance and restricted entry by brain barriers.RTG is dopamine (D1-D5) &5HT1A agonist and α-2 adrenergic receptors antagonist. In present research, RTG loaded Solid Lipid Nanoparticles (RTG-SLNs) was optimized to improve bioavailability via. nose to brain delivery. Quality by Design approach for the product development was used. Dynasan 118 as solid lipid and tween 80 as surfactant were optimized. RTG-SLNs were prepared by hot melt emulsification method using high speed homogenizer. Amongst various independent variables, critical variables were selected using 25−2 Fractional Factorial Design. Further optimization was done using central composite design. Design results were analyzed using ANOVA, Pareto chart, surface plots and desirability. Optimized RTG-SLNs gave desired particle size (129 nm), % Entrapment Efficiency (83%), Polydispersivity index (0.285), zeta potential (−23.1) and in-vitro drug release in phosphate buffer 7.4 for 30 h (99%). Further optimized batch was characterized using FTIR, TEM and AFM. From the ex-vivo permeability, cellular uptake study (confocal laser scanning microscopy) and histopathology study, RTG-SLNs was found permeable through goat nasal mucosa and non-toxic. Formulation was found stable during 3 months’ stability studies at refrigerated condition.

PEG-interpenetrated genipin-crosslinked dual-sensitive hydrogel/nanostructured lipid carrier compound formulation for topical drug administration

PEG-interpenetrated dual-sensitive hydrogels that load nano lipid carrier (NLC) were researched and developed for topical drug administration. Natural antioxidant α-lipoic acid (ALA) was selected as our model drug. The α-lipoic acid (ALA) nano lipid carrier was successfully prepared by hot melt emulsification and ultrasonic dispersion method, and the physicochemical properties of the nano lipid carrier were investigated, including morphology, particle distribution, polydispersity coefficient, zeta potential and encapsulation efficiency. Carboxymethyl chitosan and poloxamer 407 contributed to pH- and temperature-sensitive properties in the hydrogel, respectively. Natural non-toxic cross-linking agent genipin reacted with carboxymethyl chitosan to form the hydrogel. Poly ethylene glycol (PEG), a polymer compound with good water solubility and biocompatibility, interpenetrated the hydrogel and influenced the mechanical strength and drug release behaviour. FI-IR test verified the successful synthesis of the hydrogel. The rheological parameters indicated that the mechanical strength of the hydrogel was positively correlated with the amount of PEG, and the in vitro dissolution profiles demonstrated that the increasement of PEG could accelerate the drug release rate. The compatibility of the drug delivery system was verified with cells and mice model. Topical delivery of ALA in solution, NLC and NLC-gel was investigated in-vitro.