SLN Formulations Research Articles

Preparation, Characterization, and Antiangiogenic Evaluation of a Novel 5-Fluorouracil Derivative Solid Lipid Nanoparticle with a Hen's Egg Chorioallantoic Membrane Assay and Wound Healing Response in HaCaT Keratinocytes.

5-Fluorouracil is a heterocyclic aromatic organic compound, and it is commonly used as a chemotherapeutic agent in many cancers. The present goal is to analyze and characterize the physicochemical and biological properties of a new therapeutic formulation of 5-FUD-Gal under simulated chronic wound and oxidative stress conditions. After synthesis of a new 5-fluorouracil derivative, preparation and characterization of the formulation were carried out. The antiangiogenic effect, wound healing, and oxidative stress responses were conducted with a HET-CAM assay and in vitro cell culture technique. The results initially demonstrated that 5-FUD-Gal synthesized by a series of reactions and the SLN formulation were prepared successfully. A strong cell protective effect above 98% cell viability was detected at 20 μM at 48 h. The wound closure of the HaCaT scratch assay was calculated to be 90.12 and 98.98% at 10 and 20 μM concentrations, respectively, at 48 h. Moreover, the strongest effect of 5-FUD-Gal-F was observed at 20 μM concentration on chicken embryos. This study provides novel insights that a new derivative of semisynthetic 5-FUD-Gal-F can be further evaluated as a therapeutic chemical compound in cancer disease.

Development of Gefitinib-Loaded Solid Lipid Nanoparticles for the Treatment of Breast Cancer: Physicochemical Evaluation, Stability, and Anticancer Activity in Breast Cancer (MCF-7) Cells.

In the current study, the toxic effects of gefitinib-loaded solid lipid nanoparticles (GFT-loaded SLNs) upon human breast cancer cell lines (MCF-7) were investigated. GFT-loaded SLNs were prepared through a single emulsification-evaporation technique using glyceryl tristearate (Dynasan™ 114) along with lipoid® 90H (lipid surfactant) and Kolliphore® 188 (water-soluble surfactant). Four formulae were developed by varying the weight of the lipoid™ 90H (100-250 mg), and the GFT-loaded SLN (F4) formulation was optimized in terms of particle size (472 ± 7.5 nm), PDI (0.249), ZP (-15.2 ± 2.3), and EE (83.18 ± 4.7%). The optimized formulation was further subjected for in vitro release, stability studies, and MTT assay against MCF-7 cell lines. GFT from SLNs exhibited sustained release of the drug for 48 h, and release kinetics followed the Korsmeyer-Peppas model, which indicates the mechanism of drug release by swelling and/or erosion from a lipid matrix. When pure GFT and GFT-SLNs were exposed to MCF-7 cells, the activities of p53 (3.4 and 3.7 times), caspase-3 (5.61 and 7.7 times), and caspase-9 (1.48 and 1.69 times) were enhanced, respectively, over those in control cells. The results suggest that GFT-loaded SLNs (F4) may represent a promising therapeutic alternative for breast cancer.

Evaluation of Oral Bioavailability and In-vivo Anti-leukemic Potential of Dasatinib Loaded Solid Lipid Nanoparticles

Dasatinib is one of the second-generation tyrosine kinase inhibitors (TKI) that is taken orally and has antiproliferative activity against chronic myeloid leukemia (CML). Dasatinib/hesperidin loaded-SLNs were synthesized in-house using a high-shear homogenizer and optimized by central composite design (CCD). Oral bioavailability and in-vivo anti-leukemic potential of developed dasatinib/hesperidin-loaded-solid lipid nanoparticles (SLNs) were determined using intravenous injection of leukemia cells in mice model. Dasatinib was administered as pure drug (suspension) and SLN formulation in leukemic mice modal. The pharmacokinetic profile was studied and compared with drug suspension using HPLC. Results denoted mean maximum plasma concentrations Cmax as 184.52 and 390.43 ng/mL, mean Tmax as 2 and 4 hours, mean half-life as 4.63 and 8.06 hours., for pure drug (suspension) and SLN formulation, respectively. The mean area under the curve (AUClast) was 1080.94 and 3669.49 hr*ng/mL for the same. SLN also showed statistically significant survival. A comparison of SLN and free drugs revealed that SLN was more effective at cytotoxicity. Therefore, the developed dual-targeted SLN formulation of dasatinib demonstrated higher sensitivity of cells to the drug entrapped in SLN than the drug suspension.

Dasatinib and Hesperidin Loaded Nano Formulation and Preclinical Evaluation for Anticancer Activity

In this study, we aimed to develop Dasatinib/hesperidin-loaded-SLNs for chronic myeloid leukemia (CML). Utilizing a high-shear homogenizer for the synthesis, “central composite design (CCD)” was used to enhance the dasatinib/hesperidin loaded-SLNs. The optimized SLNs had PDI, particle size, and average entrapment efficiency of 0.12%, 162.3 nm, and 93%, respectively. Therefore, by enhancing the total amount of Compritol as well as sonication time the polydispersity was increased. Poloxamer 188 content had a significant influence in decreasing the polydispersity index and the entrapment efficiency (EE) of the SLN was found to be 93%. Through TEM, SEM, FTIR, DSC, and HPLC analysis, SLNs were characterized, and their anticancer efficiency was assessed in both in-vitro and in-vitro cell viability tests (MTT). SLNs containing dasatinib and hesperidin have rounded and spherical shape having a diameter of 200 nm. DSC and FTIR tests showed compatibility between the drugs and excipients. The drug release from optimized SLN formulation was under observation for 48 hours. It was found that the medication released its drug components over a protracted period of time, with 30% of the drug being released in the first four hours and the remainder 76% in the next 48 hours. According to the IC50 values determined by an independent study, dasatinib, hesperidin, and SLN were 33.97, 5158, and 4.03 μg/mL, respectively. A comparison of SLN and free drugs revealed that SLN was more effective at cytotoxicity. In this study, dasatinib and hesperidin-loaded SLNs for chronic myeloid leukemia (CML) against HL60 human leukemia cell lines were prepared and evaluated using a novel formulation approach free of toxic excipients.

Anti-obesity effects of chlorogenic acid and caffeine- lipid nanoparticles through PPAR-γ/C/EBP-ɑ pathways.

Obesity is considered one of the most crucial health problems of the century. Therefore, reducing obesity is critically important. Caffeine (CF) and chlorogenic acid (CLA), which are substantial components in green bean coffee which maximize thermogenesis in brown adipose tissue. In our study, we have prepared CF, CLA, and CF + CLA loaded-solid lipid nanoparticles (SLN) since the SLNs are cost-effective, tissue-localized, and highly stable. The central composite design model was preferred to select the optimized formulation. UHPLC was used for quantification related to the CF and CLA amounts. The high-pressure homogenization (HPH) method was used while SLN formulations were prepared in the presence of poloxamer® 407 (surfactant) and Compritol® 888 ATO (solid lipid). The nanoparticles were characterized, followed by the utilization of 3T3-F442A cell lines for the evaluation of the adipogenesis activity of the formulations. Then, rt-PCR and ELISA studies of adipogenic markers were conducted. After optimal formulations were selected with an average of 110.2 ± 0.1 nm, CF (1 mM) + CLA (0.5 mM)-loaded SLN formulation has been proven significantly effective by using PPAR-γ/C/EBP-a pathways. In a nutshell, our study has shown that CF + CLA loaded-SLN has been affected 45.8% times more than regular extracted coffee (p < 0.05) on the adipocyte cells.

Effect of Surfactant on controlling the Size of Octadecylamine-based Solid Lipid Nanoparticles and Toxicity

Surfactants play a major role in solid lipid nanoparticles’ (SLNs) composition and properties, especially in terms of particle size and zeta potential. Not only the type of the surfactants but also their amounts and chemical compatibility with the lipid core within the formulation cause good changes. In this study, our goal was to determine the effect of tween 80 (a non-ionic surfactant) on octadecylamine (cationic lipid)-based SLN formulation and its influence on SLNs properties. Also, we examined the effect of sonication and filtration as mechanical forces on the particle size, zeta potential and PDI features. Five different formulations were performed by the emulsion solvent evaporation method. Particle size distribution, zeta potential and PDI values were determined by Zetasizer via the dynamic light scattering method. We obtained SLNs resulting from different formulations and one formulation was selected with the most suitable properties for further studies. The stability of the SLNs was examined by incubating them at 4 °C in the dark for particular time intervals and the results revealed not only minimal changes in particle size but also no significant changes in zeta potential and PDI values. The nanoparticles were characterized morphologically with Transmission electron microscopy (TEM) and Atomic force microscopy (AFM). The chemical characterization was performed by Fourier-transform infrared spectroscopy (FT-IR). In vitro cytotoxicity via MTT assay on L929 mouse fibroblast cell line was performed and cell viability was determined over 63% for all concentrations.

Polyphyllin D-loaded solid lipid nanoparticles for breast cancer: Synthesis, characterization, in vitro, and in vivo studies

Polyphyllin D (PD), a steroidal saponin in Paris polyphylla, induces apoptosis via the intrinsic apoptotic pathway in different cancer types. However, emerging evidence has shown that the primary issue with PD is its structure's hemolysis and cytotoxicity. This study aimed to develop and optimize PD-loaded SLN formulation and evaluate its efficacy in breast cancer cell lines. Apoptosis, as the mechanism of cell death, was confirmed by flow cytometry following Annexin V/propidium iodide staining and western blot analysis. In in vivo studies, tumor inhibitory efficacy was compared with different doses of PD-loaded SLN on 4T1-implanted BALB/c mice. The half-maximal inhibitory concentration (IC50) of PD- loaded SLN was calculated to be 33.25 and 35.74 μg/mL for MCF7 and MDA-MB-231 cells, respectively. Flow cytometry analysis further confirmed a significant increase in apoptosis after treatment with PD- loaded SLN. When both cell lines were treated with PD-loaded SLN, Bcl2 and HSP70 proteins were down regulated, while Bax, Bad, P53, Apaf-1, p-p53 and Noxa proteins were upregulated. This effect was also confirmed by test performed on BALB/c mice in vivo. Based on results, PD-loaded SLN may be a promising breast cancer treatment, without recognizable side effects.

Design and Preclinical Evaluation of Nicotine-Stearic Acid Conjugate-Loaded Solid Lipid Nanoparticles for Transdermal Delivery: A Technical Note.

This study aimed to develop and evaluate nicotine--stearic acid conjugate-loaded solid lipid nanoparticles (NSA-SLNs) for transdermal delivery in nicotine replacement therapy (NRT). Nicotine conjugation to stearic acid prior to SLN formulation greatly increased drug loading. SLNs loaded with a nicotine-stearic acid conjugate were characterized for size, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, and morphology. Pilot in vivo testing was carried out in New Zealand Albino rabbits. The size, PDI, and ZP of nicotine-stearic acid conjugate-loaded SLNs were 113.5 ± 0.91 nm, 0.211 ± 0.01, and -48.1 ± 5.75 mV, respectively. The entrapment efficiency of nicotine-stearic acid conjugate in SLNs was 46.45 ± 1.53%. TEM images revealed that optimized nicotine-stearic acid conjugate-loaded SLNs were uniform and roughly spherical in shape. Nicotine-stearic acid conjugate-loaded SLNs showed enhanced and sustained drug levels for up to 96 h in rabbits when compared with the control nicotine formulation in 2% HPMC gel. To conclude, the reported NSA-SLNs could be further explored as an alternative for treating smoking cessation.

Myricetin loaded in solid lipid nanoparticles induces apoptosis in the HT-29 colorectal cancer cells via mitochondrial dysfunction.

Among the flavonoids, Myricetin (MCN) has negligible side effects and anti-cancer properties. However, the therapeutic potential of MCN has been limited mainly by its low bioavailability. Nanocarriers improve the bioavailability and stability of flavonoids. The toxic effects of MCN loaded in solid lipid nanoparticles (MCN-SLNs) on the HT-29 human colorectal cancer cells were investigated in this study. HT-29 cells were exposed to the 30µmol MCN or MCN-SLNs for 24h. Colony formation, cell viability, apoptosis, and expression of the Bax, Bcl-2, and AIF (apoptosis-inducing factor) have been investigated. Mitochondrial membrane potential(MMP) andreactive oxygen species(ROS) generation were also measured. The MCN-SLNs with appropriate characteristics and a slow sustained MCN release until 48h made. MCN-SLNs could diminish colony numbers and survival of the HT-29 cells. The apoptosis index of MCN-SLNs-treated cells significantly increased compared to the free MCN (p < 0.001). The expression of Bax and AIF were elevated (p < 0.01 and p < 0.001, respectively) while Bcl-2 expression was decreased in MCN-SLNs treatment (p < 0.05). Moreover, MCN-SLNs significantly enhanced the ROS formation and reduced MMP compared to the free MCN-treated cells (p < 0.01). The SLN formulation of MCN can effectively induce colon cancer cell death by raising ROS formation and activating the apoptosis process.

DONEPEZIL HYDROCHLORIDE LOADED SOLID LIPID NANOPARTICLES: FORMULATION, IN VITRO–IN VIVO PHARMACOKINETIC AND PHARMACODYNAMICS EVALUATION

Objective: The aim of the present study was to design and in vitro–in vivo evaluation of Donepezil Hydrochloride solid lipid nanoparticles (DHSLN). Methods: A modified solvent injection method was used to produce Donepezil-loaded solid lipid nanoparticles. A Response Surface Method 3-factor, 2-level Box-Behnken design was applied to study the effect of independent variables on dependent variables. Then it was coated with tween 80 for ease of permeability through the blood-brain barrier due to intact absorption of solid lipid nanoparticles. The prepared SLN was evaluated for particle size, zeta potential analysis, Entrapment efficiency, In vitro drug release study, Field Emission-scanning electron microscopy, In vivo Pharmacokinetic and Pharmacodynamics studies. Results: The results of coated optimized formulation showed an average particle size of 185.8 nm, entrapment efficiency of 78.52±2.54%, and in vitro drug release of 98.62±3.14% at 36h at pH 7.4. The pharmacokinetic data show higher Cmax and improved bioavailability, which was also supported by behavioural changes observed in locomotor activity for surface-modified SLN formulation. Conclusion: Thus, the current study successfully designed, developed an optimized SLN formulation. The surface-modified SLN proved to enhance the permeability of the drug through barrier, which led to the enhancement of Donepezil bioavailability and locomotor activity.

Synthesis and In Vitro Characterization of Ascorbyl Palmitate-Loaded Solid Lipid Nanoparticles.

Antitumor applications of ascorbic acid (AA) and its oxidized form dehydroascorbic acid (DHA) can be quite challenging due to their instability and sensitivity to degradation in aqueous media. To overcome this obstacle, we have synthesized solid lipid nanoparticles loaded with ascorbyl palmitate (SLN-AP) with variations in proportions of the polymer Pluronic F-68. SLNs were synthesized using the hot homogenization method, characterized by measuring the particle size, polydispersity, zeta potential and visualized by TEM. To investigate the cellular uptake of the SLN, we have incorporated coumarin-6 into the same SLN formulation and followed their successful uptake for 48 h. We have tested the cytotoxicity of the SLN formulations and free ascorbate forms, AA and DHA, on HEK 293 and U2OS cell lines by MTT assay. The SLN-AP in both formulations have a cytotoxic effect at lower concentrations when compared to ascorbate applied the form of AA or DHA. Better selectivity for targeting tumor cell line was observed with 3% Pluronic F-68. The antioxidative effect of the SLN-AP was observed as early as 1 h after the treatment with a small dose of ascorbate applied (5 µM). SLN-AP formulation with 3% Pluronic F-68 needs to be further optimized as an ascorbate carrier due to its intrinsic cytotoxicity.

Impact of highly phospholipid-containing lipid nanocarriers on oral bioavailability and pharmacodynamics performance of genistein

Oxidative stress is a leading cause of different diseases. Genistein is a valuable bioflavonoid possessing antioxidant and anti-inflammatory activity but unfortunately, it suffers from low aqueous solubility, extremely poor bioavailability and first pass effect when used in its pure state. The aim of this work was to formulate and characterize genistein-loaded highly phospholipid-containing lipid nanocarriers to improve oral bioavailability and pharmacodynamic performance. Lipid nanocarriers were prepared by the emulsification/sonication technique. The influence of phospholipid percentage (1%–10%) on physicochemical properties, drug release and stability was investigated. The particle size, zeta potential and EE% were in ranges from 211.9 ± 21.6 to 342.3 ± 7.9 nm, −11.6 ± 1.7 to −19.4 ± 3.1 mV and 78.5 ± 4.7% to 92.2 ± 1.9%, respectively. Drug release was less predominant in the case of SLN formulations when compared to corresponding NLC formulations. High phospholipid percentage produced less stable formulations in terms of particle size growth, gelation and heterogeneous particle distributions. DSC, FT-IR and XRD tools revealed that genistein has existed in an amorphous form in NLC4. The bioavailability of NLC4 was approximately 2.6-fold greater than that of conventional suspension. Additionally, lipid peroxidation in liver homogenate and histopathological alterations in liver and kidney sections were particularly improved, providing a promising strategy for oral administration of genistein.

Preparation and Evaluation of Efavirenz Loaded Solid Lipid Nanoparticle for improving Oral Bioavailability

Efavirenz (EFV) is a highly lipophilic, oral non-nucleoside reverse transcriptase inhibitor reported to have poor aqueous solubility and bioavailability used for the treatment of HIV. In the present research work, solid lipid nanoparticles loaded with efavirenz were formulated for oral drug delivery and to increase the bioavailability of efavirenz. Solid lipid nanoparticles loaded with efavirenz were prepared through the microemulsion method followed by the lyophilization technique using glyceryl monostearate as lipid and Tween 80 as a surfactant. Solid lipid nanoparticle formulation was evaluated using different parameters including Scanning electron microscopy (SEM), drug entrapment efficiency (EE%), in vitro drug release study, differential scanning calorimetry, and powder X-ray diffractometry. Solid lipid nanoparticles loaded efavirenz showed 60.41% drug entrapment. Differential scanning calorimetry and powder X-ray diffractometry study indicate solid lipid nanoparticles loaded efavirenz is crystalline, stable and there is no interaction between the excipients and drug. In vitro drug release study of EFV-SLN showed 88.2±0.12% drug release which is better as compared to marketed formulation drug release. EFV-SLN drug release study data demonstrated a better fit for the first-order kinetics and confirmed the non-Fickian-diffusion mechanism. Prepared SLN formulation has shown good stability at 45∘C and 75% relative humidity (RH) for 150 days. These results determined that the developed EFV-SLN formulation exhibited a promising antiviral activity to treat HIV and has great potential for boosting the oral bioavailability of Efavirenz.

Mechanistic evaluation of lymphatic targeting efficiency of Atazanavir sulfate loaded lipid nanocarriers: In-vitro and in-vivo studies

In the present study, Atazanavir sulfate-loaded solid lipid nanoparticles (ATZ-SLNs) were developed and characterized for oral bioavailability enhancement and lymphatic absorption. ATZ-SLNs were formulated by emulsion-solvent evaporation technique using hydrogenated castor oil and sodium oleate. The optimized formulation had a mean particle size of 190.1 ± 2.45 nm, the zeta potential of −42.63 ± 2.46 mV and entrapment efficiency of 94.26 ± 2.12%. Transmission electron microscopy and Field emission-scanning electron microscopy morphology indicated discrete and round structures without aggregation. In-vitro drug release study showed controlled drug release of 80.36% in 12 h in simulated intestinal fluid. Cell-line study in Caco-2 cells showed increased permeability upon SLN formulation and mode of cellular uptake of SLN as clathrin and caveoli mediated endocytosis. In-vivo pharmacokinetic study in rats indicated increased oral bioavailability using ATZ-SLNs by 200% compared to suspension formulation. A lymphatic transport study revealed that SLNs were transported via lymphatic vessels. In organ biodistribution study, peyer's patch region showed a 4.5 fold higher uptake of ATZ through ATZ-SLNs formulation than non-peyer's patch region and high accumulation in spleen and brain. This delivery approach could maximize the drug concentrations to the lymphatic system leading to effective therapy for HIV.

In vitro release, ex vivo penetration, and in vivo dermatokinetics of ketoconazole-loaded solid lipid nanoparticles for topical delivery.

The study focused to evaluate and investigate optimized (using QbD) and novel ketoconazole (KTZ)-loaded solid lipid nanoparticles (KTZ-SLNs; 2% w/v KTZ) for enhanced permeation across skin. KTZ-SLNs were evaluated for size, distribution, zeta potential (ZP), percent entrapment efficiency (%EE), drug release, morphology (HRTEM and FESEM), thermal behaviour (DSC), spectroscopic (FTIR), and solid-state/diffraction characterization (X-ray diffraction, XRD). Moreover, ex vivo permeation and drug deposition into rat skin were conducted using Franz diffusion cell. The same was confirmed using human dermatome skin and fluorescence, confocal Raman, and vibrational ATR-FTIR microscopic methods. An in vivo dermatokinetics study was performed in rats to assess the extent of KTZ permeation into the skin. Stability including accelerated and photostability studies were conducted at different temperatures (2-8, 30, and 40°C) for 12months. The spherical, optimized KTZ-SLN formulation (KOF1) showed particle size of 293nm and high EE of 88.5%. Results of FTIR, DSC, and XRD confirmed formation of KTZ-SLNs and their amorphous nature due to presence of KTZ in a dissolved state in the lipid matrix. In vitro release was slow and sustained whereas ex vivo permeation parameters were significantly high in KTZ-SLNs as compared to free drug suspension (KTZ-SUS) and marketed product (Nizral®; 2% KTZ w/v). Drug retention was 10- and five-fold higher than KTZ-SUS and marketed product, respectively. In vivo dermatokinetics parameters improved significantly with SLN formulation (410-900% enhanced). Confocal Raman spectroscopy experiment showed that KTZ-SLNs could penetrate beyond the human stratum corneum into viable epidermis. Fluorescent microscopy also indicated improved penetration of KTZ-SLNs. KTZ-SLNs were photostable and showed long-term stability over 12months under set conditions.

Surface Modification of Optimized Asenapine Maleate Loaded Solid Lipid Nanoparticles Using Box-Behnken Design

Aim: The aim of the present study was to design and evaluate solid lipid nanoparticles of Asenapine maleate (&lt;2% bioavailability) to enhance its oral bioavailability and surface modification for brain targeting.&#x0D; Methods: A modified solvent injection method was used to produce Asenapine maleate loaded solid lipid nanoparticles. A RSM 3-factor, 3-level Box-Behnken design was applied to study the effect of three independent variables, concentrations of lipid (A), drug (B) and surfactant (C) on three dependent variables, particles size (Y1), entrapment efficiency (Y2), and drug release (Y3). 3-D surface response plots were drawn and optimized formulation was selected based on desirability factor. Then it was coated with tween 80 for ease of permeability through blood brain barrier due to intact absorption of solid lipid nanoparticles.&#x0D; Results: The results of coated optimized formulation showed average particle size of 108.9 nm, entrapment efficiency of 78.62%, and in vitro drug release of 98.88±0.102% at 36 hr at pH 7.4. Morphologically, particles were almost spherical in shape with uniform size distribution. Targeting of coated optimized formulation to brain after oral administration was confirmed by fluorescence microscopy studies on male albino wistar strain rats. This research also envisaged that there is a &gt;85% cell viability up to 125µg/ ml concentration of coated solid lipid nanoparticles by MTT assay.&#x0D; Conclusion: Thus, the current study successfully designed, developed an optimized SLN formulation of Asenapine maleate using a 3-factor, 3-level Box-Behnken design for brain targeting to treat Schizophrenia by bypassing the first pass metabolism with enhanced oral bioavailability.

Raloxifene-loaded SLNs with enhanced biopharmaceutical potential: QbD-steered development, in vitro evaluation, in vivo pharmacokinetics, and IVIVC.

Raloxifene hydrochloride, a second-generation selective estrogen receptor modulator, has been approved for the management of breast cancer. However, it is known to exhibit poor (~ 2%) and inconsistent oral bioavailability in humans, primarily ascribable to its low aqueous solubility, extensive first-pass metabolism, P-gp efflux, and presystemic glucuronide conjugation. The present research work entails the systematic development and evaluation of SLNs of RLX for its enhanced biopharmaceutical performance against breast cancer. Factor screening studies were conducted using Taguchi design, followed by optimization studies employing Box-Behnken design. Preparation of SLNs was carried out using glyceryl monostearate and Compritol® 888 ATO (i.e., lipid), Phospholipid S-100 (i.e., co-surfactant), and TPGS-1000 (i.e., surfactant) employing solvent diffusion method. The optimized formulation was evaluated for zeta potential, average particle size, field emission scanning electron microscope, transmission electron microscopy, and in vitro release study. Further, MCF-7 cells (cell cytotoxicity assay, apoptosis assay, and reactive oxygen species assay) and Caco-2 cells (cell uptake studies and P-gp efflux assay) were employed to evaluate the in vitro anticancer potential of the developed optimized formulation. In vivo pharmacokinetic studies were conducted in Sprague-Dawley rats to evaluate the therapeutic profile of the developed formulation. The optimized SLN formulations exhibited a mean particle size of 109.7nm, PDI 0.289 with a zeta potential of - 13.7mV. In vitro drug dissolution studies showed Fickian release, with release exponent of 0.137. Cell cytotoxicity assay, apoptosis assay, and cellular uptake indicated 6.40-, 5.40-, and 3.18-fold improvement in the efficacy of RLX-SLNs vis-à-vis pure RLX. Besides, the pharmacokinetic studies indicated quite significantly improved biopharmaceutical performance of RLX-SLNs vis-à-vis pure drug, with 4.06-fold improvement in Cmax, 4.40-fold in AUC(0-72h), 4.56-fold in AUC(0-∞), 1.53-fold in Ka, 2.12-fold in t1/2, and 1.22-fold in Tmax. Further, for RLX-SLNs and pure drug, high degree of level A linear correlation was established between fractions of drug dissolved (in vitro) and of drug absorbed (in vivo) at the corresponding time-points. Stability studies indicated the robustness of RLX-SLNs when stored at for 3months. Results obtained from the different studies construe promising the anticancer potential of the developed RLX-SLNs, thereby ratifying the lipidic nanocarriers as an efficient drug delivery strategy for improving the biopharmaceutical attributes of RLX.

Solid-lipid nanoparticle formulation improves antiseizure action of cryptolepine

Following the high treatment gap and massive impact of epilepsy on global health particularly in low- and middle-income countries, our study aims to investigate cryptolepine, the major alkaloid of Cryptolepis sanguinolenta as well as its solid-lipid nanoparticle formulation for potential antiseizure activity. Cryptolepine was isolated and a solid-lipid formulation was prepared. Antiseizure activity of Solid-Lipid Nanoparticle formulation of cryptolepine (SLN-CRYP) was investigated using Pentylenetetrazole (PTZ)-induced model of seizure-like behaviors in Zebrafish with 2.5 and 5 mg/kg each of cryptolepine and SLN-CRYP. Drug receptor binding and permeability of the compound across the Blood Brain Barrier (BBB) were also assessed. SLN formulation of cryptolepine increased its permeability to the BBB from 0.32 × 10−6 cm/s to 10.81 × 10−6 cm/s. 2.5 and 5 mg/kg of SLN-CRYP significantly reduced mean seizure score (P = 0.0018; F(6, 63) = 23.52) and significantly increased (P < 0.0001; F(6, 63) = 65.41) latency to onset of seizures. The total distance swam by fish administered with 2.5 and 5 mg/kg of SLN-CRYP was significantly (P < 0.000; F(6, 63) = 161.9) decreased. 5 mg/kg of cryptolepine also significantly decreased swimming distance. Cryptolepine exhibited inhibitory modulation of human voltage-gated calcium channels (Cav1.2), H1-receptor, Peripheral Benzodiazepine Receptor and Sigma 2 receptor with a high Ki values of 6133.38 nM and 2945.0 nM, indicating less potent antagonism on Cav1.2 and Sigma 2 receptors compared to Nifedipine and Haloperidol respectively. This study reveals that the solid-lipid nanoparticle formulation of cryptolepine improves its BBB permeability and hence antiseizure activity.

Topical arginine solid lipid nanoparticles: Development and characterization by QbD approach

The application of l-arginine, the nonessential amino acid, as in pharmaceutical and cosmetics is raised as it shows the number of advantages for internal and external, applications. But its hydrophilic nature and lower partition co-efficient value limit its penetration through the skin. From the different approaches for topical drug delivery systems, solid lipid nanoparticles are a promising vehicle to carry the drug molecule at the appropriate site of absorption and also ensures the fast therapeutic action. With ability to incorporate lipophilic as well as a hydrophilic molecule. The present investigation aimed to implement the Quality by design concept for the development of SLNs incorporated with arginine molecule for its application on skin in the form of cosmoceutical formulation. The developed formulation will enhance the blood circulation of skin cells and hence beneficial for skin as cosmoceutical dosage form. To enhance the loading of drug molecule in a lipolphilic environment like solid lipid, insitu ion-pairing was carried out using an optimum concentration of oleic acid. The optimization was done by QbD approach considering concentration of poloxamer 188, oleic acid and sonication amplitude as the critical processing parameters. Average particle size and % drug loading were taken as critical product quality attributes using 23 full factorial design. The characterization of freeze dried solid lipid nanoparticles are investigated by transmission electron microscopy, x-ray diffraction study, differential scanning calorimetry and fourier transform infrared spectroscopy. Finally, an in-vitro and ex-vivo drug diffusion stuies were carried out to check the permeation of arginine. The optimized SLN formulation were successfully developed having lower particle size and higher % drug loading with effective skin penetration parameters to achieve the therapeutic benefits of Arginine.

Optimization and screening of solid lipid nanoparticle production for gene delivery by factorial design and response surface methodology

Aim: A successful gene therapy requires a delivery system for overcoming various biological barriers. For this, we adapted the factorial design and response surface methodology to the cationic solid lipid nanoparticle production process. Methods: Screening and optimization of formulations were carried out with factorial design with 3 factors and 3 levels using Box-Behnken Design. Then, solid lipid nanoparticles were physicochemically characterized. Furthermore, optimal SLN formulation is examined in terms of complex formation with plasmid DNA, its protection potential against nucleases, cytotoxicity profile, and storage stability. Results: Response-surface analyses demonstrated that the selected quadratic model holds significance for particle size and zeta potential. The interaction of independent variables was statistically determined. Optimization and prediction were performed using obtained second-order polynomial equations. Optimal formulation and complexes were found to be nanosized, positively charged and their polydispersity-index values below 0.3 as an indicator of being monodispersed. Cytotoxicity of the optimal formulation is compatible for further studies and no significant increase was observed in particle size until day 21 and until day 60 for polydispersity-index. Conclusion: Optimal formulation provides a good basis as a gene delivery system was produced with developed systematic. Briefly, this methodology could be used to obtain SLNs with desired conditions.