Transcutol HP Research Articles

Antifungal Activity of Piperine-based Nanoemulsion Against Candida spp. via In Vitro Broth Microdilution Assay

Candidemia leaves a trail of approximately 750,000 cases yearly, with a morbidity rate of up to 30%. While Candida albicans still ranks as the most predominantly isolated Candida species, C. glabrata comes in second, with a death rate of 40–50%. Although infections by Candida spp are commonly treated with azoles, the side effects and rise in resistance against it has significantly limited its clinical usage. The current study aims to address the insolubility of piperine and provide an alternative treatment to Candida infection by formulating a stable piperine-loaded O/W nanoemulsion, comprised of Cremophor RH40, Transcutol HP and Capryol 90 as surfactant, co-surfactant, and oil, respectively. Characterization with zetasizer showed the droplet size, polydispersity (PDI) and zetapotential value of the nanoemulsion to be 24.37 nm, 0.453 and -21.10 mV, respectively, with no observable physical changes such as phase separation from thermostability tests. FTIR peaks confirms presence of piperine within the nanoemulsion and TEM imaging visualized the droplet shape and further confirms the droplet size range of 20–24 nm. The MIC90 value of the piperine-loaded nanoemulsion determined with in vitro broth microdilution assay was approximately 20–50% lower than that of the pure piperine in DMSO, at a range of 0.8–2.0 mg/mL across all Candida spp. tested. Overall, the study showed that piperine can be formulated into a stable nanoemulsion, which significantly enhances its antifungal activity compared to piperine in DMSO.

Formulation, Optimization and Evaluation of Dabigartan Etexilate Encapsulated Solid Supersaturated Self-Nanoemulsifying Drug Delivery System

Objective: The present study proposed Dabigatran Etexilate loaded solid supersaturat-ed self-nanoemulsifying drug delivery system (solid S-SNEDDS) for enhancement of payload, drug solubility, dissolution rate as well as minimization of drug precipitation. Methods: The study involved formulation optimization using the Box-Behnken design. The op-timal SNEDDS consisting of Caprylic acid (32.9% w/w), Cremophor EL (50.2% w/w) and Transcutol HP (18.8% w/w) as Oil, Surfactant and Co-surfactant, respectively were formulated and evaluated for particle size, PDI, Zeta potential and saturation solubility. The SNEDDS was further incorporated with PPIs for the preparation of supersaturated SNEDDS (S-SNEDDS) to in-crease the drug payload in the formulation. S-SNEDDS was converted to solid S-SNEDDS by ad-sorption onto the porous carrier i.e., Aerosil®200. The in-vitro drug release study was also con-ducted for solid S-SNEDDS. Results: SNEDDS had size, PDI, and Zeta potential of 82 nm, 0.347, -10.50 mV, respectively. SNEDDS enhanced the saturation solubility of the drug by 93.65-fold. Among PPIs, HPMC K4M showed the most effective response for the formulation of S-SNEDDS. The S-SNEDDS had a more substantial drug payload, which further increased the solubility by 150 times of pure drugs and 16 times of SNEDDS. Solid S-SNEDDS exhibited free-flowing properties. Reconstituted sol-id S-SNEDDS had acceptable size, PDI, and Zeta potential of 131.3 nm, 0.457, and -11.3 mV, respectively. In-vitro drug release study revealed higher drug dissolution and minimized drug pre-cipitation by SNEDDS compared to marketed products and pure drugs. Conclusion: Proposed nano-formulation was found to efficiently improve the aqueous solubility of the drug and avoid the drug precipitation, thereby avoiding drug loss and improving drug bioa-vailability.

Self Emulsifying Delivery System of Cissus quadrangularis: Evidence of Enhanced Efficacy and Promising Pharmacokinetic Profile in the Management of Osteoporosis.

Treatment therapies used to manage osteoporosis are associated with severe side effects. So worldwide herbs are widely studied to develop alternative safe & effective treatments. Cissus quadrangularis (CQ) has a significant role in bone health and fracture healing. It is documented that its extracts increase osteoblastic differentiation & mineralization. Currently, Cissus quadrangularis is available in the form of tablets in the market for oral delivery. But these conventional forms are associated with poor bioavailability. There is a need for a novel drug delivery system with improving oral bioavailability. Therefore, a Cissus quadrangularis-loaded self-emulsifying drug delivery system (CQ-SEDDS) was developed which disperses rapidly in the gastrointestinal fluids, yielding nano-emulsions containing a solubilized drug. This solubilized form of the drug can be easily absorbed through lymphatic pathways and bypass the hepatic first-pass effect. The emulsification efficiency, zeta potential, globule size, in-vitro dissolution, ex-vivo, in-vivo and bone marker studies were performed to assess the absorption and permeation potential of CQ incorporated in SEDDS. CQ-SEDDS with excipients Tween 80, Cremophor RH40, Transcutol HP & α-Tocopherol acetate had shown about 76% enhancement in the bioavailability of active constituents of CQ. This study provided the pre-clinical data of CQ-SEDDS using osteoporotic rat model studies.

DEVELOPMENT AND OPTIMIZATION OF SUPER SATURABLE SELF-NANO EMULSIFYING DRUG DELIVERY SYSTEM FOR DASATINIB BY DESIGN OF EXPERIMENT

Objective: In current research, Self-Nanoemulsifying Super Saturable Drug Delivery Systems S‑SNEDDS was formulated to attain superior drug dissolution and stability. Methods: Using saturated solubility, capryol ® 90, cremophor®-EL, and transcutol HP were used to make S-SNEDDS. Its composition was optimized using the ternary phase diagram. Using the central composite design of Response Surface Methodology, dasatinib-SNEDDS developed responses for droplet size (Y1), polydispersity index (Y2), and % drug released in 15 min (Y3). Various Precipitation Inhibitors were added to optimize SNEDDS (S3) to make S-SNEDDS and evaluate. Results: The optimum formulation was S3, with a particle size of 128 nm and zeta potential of-21 mV. Methylcellulose was shown better supersaturation than other inhibitors. The optimized formulation (F3) was more stable than ordinary SNEDDS due to its more significant zeta potential (-25 mV) and lower particle size (128 nm). Dasatinib was shown to be amorphous in S-SNEDDS using Differential Scanning Calorimetry and X-ray Powder Diffraction. F3 had a higher 90 min release rate (>99%) than pure drug dispersion (26%) and SNEDDS formulation (95%). Conclusion: The results concluded that S-SNEDDS formulation successfully enhanced the dissolution and stability of dasatinib.

Design and evaluation of nanostructured lipid carrier of Bergenin isolated from Pentaclethra macrophylla for anti-inflammatory effect on lipopolysaccharide-induced inflammatory responses in macrophages

Herein, we report the properties of nanostructured lipid carriers (NLCs) prepared with a gradient concentration of Bergenin (BGN) isolated from Pentaclethra macrophylla stem bark powder. A gradient concentration of BGN (BGN 0, 50, 100, 150, and 200 mg) was prepared in a 5 % lipid matrix consisting of Transcutol HP (75 %), Phospholipon 90H (15 %), and Gelucire 43/01 (10 %) to which a surfactant aqueous phase consisting of Tween 80, sorbitol, and sorbic acid was dissolved. The NLCs were evaluated by size, polydispersity index (PDI), zeta potential, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), encapsulation efficiency, and in vitro drug release. The result shows polydispersed nanoparticles with high drug encapsulation (94.26–99.50 %). The nanoparticles were mostly spherical, but those from the 50 mg BGN batch were more cuboidal than spherical. The drug release was highest from the latter to the tune of 40 % compared to the pure BGN solution, which released about 15 % BGN. The anti-inflammatory activity of the BGN-NLC and total plant extract was studied on lipopolysaccharide (LPS)-inflamed macrophages. The cell study showed that BGN and plant extract had low cytotoxicity on macrophages and exhibited a dose-dependent anti-inflammatory effect on the LPS-induced inflammatory process in macrophages.

Isotretinoin self-nano-emulsifying drug delivery system: Preparation, optimization and antibacterial evaluation

PurposeIsotretinoin (ITN) is a poorly water-soluble drug. The objective of this study was to design a successful liquid self-nanoemulsifying drug delivery system (L-SNEDDS) for ITN to improve its solubility, dissolution rate, and antibacterial activity. MethodsAccording to solubility and emulsification studies, castor oil, Cremophor EL, and Transcutol HP were selected as system excipients. A pseudo ternary phase diagram was constructed to reveal the self-emulsification area. The developed SNEDDS were visually assessed, and the droplet size was measured. In vitro release studies and stability studies were conducted. The antimicrobial effectiveness against multiple bacterial strains, including Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and different accessory gene regulator (Agr) variants were investigated for the optimum ITN-loaded SNEDDS formulation. ResultsCharacterization studies showed emulsion homogeneity and stability (%T 95.40–99.20, A graded) with low droplet sizes (31.87 ± 1.23 nm–115.47 ± 0.36 nm). It was found that the developed ITN-SNEDDS provided significantly a higher release rate (>96 % in 1 h) as compared to the raw drug (<10 % in 1 h). The in vitro antimicrobial activities of pure ITN and ITN-loaded SNEDDS demonstrated a remarkable inhibitory effect on bacterial growth with statistically significant findings (p < 0.0001) for all tested strains when treated with ITN-SNEDDS as compared to the raw drug. ConclusionThese outcomes suggested that SNEDDS could be a potential approach for improving solubility, dissolution rates, and antibacterial activity of ITN.

Enhancing collagen based nanoemulgel for effective topical delivery of Aceclofenac and Citronellol oil: Formulation, optimization, in-vitro evaluation, and in-vivo osteoarthritis study with a focus on HMGB-1/RAGE/NF-κB pathway, Klotho, and miR-499a.

The majority of conventional osteoarthritis (OA) treatments are based on molecular adjustment of certain signaling pathways associated with osteoarthritis (OA) pathogenesis, however there is a significant need to search for more effective and safe treatments. This study centers around formulating Aceclofenac (ACF) with high bioavailability in combination with Citronellol oil and collagen. The optimal concentrations of Citronellol oil/D-Limonene oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were studied for thermophysical stability. Thermodynamically stable formula were analyzed for droplet size, zeta potential, and in-vitro permeation. Then, collagen based nanoemulsion were prepared to capitalize on its efficacy in reducing osteoarthritis side effects and characterized for nano size properties. Formulae F10 and F10C were chosen as optimum nanosize formula. Hense, they were prepared and characterized as nanoemulgel dosage form. The nanoemulgel formulae F10NEG1 and F10CNEG1 showed reasonable viscosity and spreadability, with complete drug release after 4h. These formulae were chosen for further In vivo anti-OA study. Collagen based ACF/citronellol emugel were able to modulate HMGB-1/RAGE/NF-κB pathway, mitigating the production of inflammatory cytokine TNF-α. They were also able to modulate Klotho and miR-499, reducing serum CTXII and COMP, by reducing the cartilage destruction. Histological investigations validated the efficacy, safety, and superiority of Aceclofenac in combination with Citronellol oil and collagen (F10CNEG1) over solo the treated group (F10NEG1 and blank). Hence, the findings of the current work encourage the use of this promising combined formula in treatment of OA patients.

Optimizing Intranasal Amisulpride Loaded Nanostructured Lipid Carriers: Formulation, Development, and Characterization Parameters

Background: Nanostructured lipid carriers (NLCs) are lipid-based nanoparticles composed of a mixture of solid and liquid lipids, which are stabilized by the outer surface of a surfactant. Objective: This research aimed to prepare intranasal nanostructured lipid carriers loaded with amisulpride to enhance its dissolution and bioavailability using different formulation compositions. Methods: Amisulpride nanostructured lipid carriers were formulated using ultra-sonication methods. Solid lipids like stearic acid, palmitic acid, and glyceryl monostearate were used, while liquid lipids like oleic acid, Imwitor 988, and isopropyl myristate were employed. Surfactants used were cremophor®EL, tween 80, and span 20 with different co-surfactants: Transcutol HP, triacetin, and propylene glycol in different ratios. The key metrics used in this study's evaluation were particle size, polydispersity index, zeta potential, entrapment efficiency, and loading efficiency. The formulations with the best characteristics were also subjected to an in-vitro release test. Results: The results showed a significant shift in some evaluation criteria with a non-significant change in other characterizations upon switching between different types and ratios of compositions. A biphasic release pattern was also observed. The optimum formula F19 was found to have 68.309±0.38 nm, 0.2408±0.004, -20.64±0.11 mV, 95.75±0.26 and 18.07±0.36, respectively. It was safe on the sheep nasal membrane. result: The results showed a significant shift in some evaluations criteria with a non-significant change in other characterizations upon switching between different types and ratios of compositions. A biphasic release pattern was also observed. The optimum formula F19 was found to have 68.309±0.38 nm, 0.204±0.004, -20.64±0.11, 95.75±0.26 and 18.07±0.36, respectively. It was safe on the sheep nasal membrane. Conclusion: The right combination of the formulation compositions based on studying the effect of each factor on the main formulation characteristics can serve as the basis for a successful intranasal amisulpride-loaded nanostructured lipid carrier.

Self-Nanoemulsion Intrigues the Gold Phytopharmaceutical Chrysin: In Vitro Assessment and Intrinsic Analgesic Effect

Chrysin is a natural flavonoid with a wide range of bioactivities. Only a few investigations have assessed the analgesic activity of chrysin. The lipophilicity of chrysin reduces its aqueous solubility and bioavailability. Hence, self-nanoemulsifying drug delivery systems (SNEDDS) were designed to overcome this problem. Kollisolv GTA, Tween 80, and Transcutol HP were selected as oil, surfactant, and cosurfactant, respectively. SNEDDS A, B, and C were prepared, loaded with chrysin (0.1%w/w), and extensively evaluated. The optimized formula (B) encompasses 25% Kollisolv GTA, 18.75% Tween 80, and 56.25% Transcutol HP was further assessed. TEM, in vitro release, and biocompatibility towards the normal oral epithelial cell line (OEC) were estimated. Brain targeting and acetic acid-induced writhing in a mouse model were studied. After testing several adsorbents, powdered SNEDDS B was formulated and evaluated. The surfactant/cosurfactant (S/CoS) ratio of 1:3 w/w was appropriate for the preparation of SNEDDS. Formula B exhibited instant self-emulsification, spherical nanoscaled droplets of 155.4 ± 32.02 nm, and a zeta potential of − 12.5 ± 3.40 mV. The in vitro release proved the superiority of formula B over chrysin suspension (56.16 ± 10.23 and 9.26 ± 1.67%, respectively). The biocompatibility of formula B towards OEC was duplicated (5.69 ± 0.03 µg/mL). The nociceptive pain was mitigated by formula B more efficiently than chrysin suspension as the writhing numbers reduced from 8.33 ± 0.96 to 0 after 60 min of oral administration. Aerosil R972 was selected as an adsorbent, and its chemical compatibility was confirmed. In conclusion, our findings prove the therapeutic efficacy of chrysin self-nanoemulsion as a potential targeting platform to combat pain.Graphical

Formulation Development, Characterization, and Therapeutic Evaluation of Ethanolic Extract of L. speciosa Leaves in Breast Cancer

Background: Due to its possible antioxidant, anti-tumor, anti-diabetic, and anti-inflammatory qualities, Lagerstroemia speciosa (Banaba) (LS) is receiving more attention in med-ical therapy. LS is a natural chemical with few adverse effects and low toxicity, although it has poor water solubility and absorption. Aims and Objectives: This study aimed to create a nanoemulsion formulation utilising an ethanol-ic extract of LS leaves and test it for anticancer activities in the MCF-7 cell line. Methods: Lemongrass oil, Cremophor EL as the surfactant, and Transcutol HP as the co-surfactant were used to create the nanoemulsion. It was done to characterize the ethanolic extract of LS leaves optimised nanoemulsion (ELSN). The MTT test against the MCF-7 cell line was used to assess the anticancer efficacy of ELSN. Results: The average particle size of the optimized nanoemulsion formulation was 91.22 nm with a PDI value of 0.224, indicating a monodispersed system. Transmission electron microscopy has validated the spherical shape of droplet size. Nanoemulsion components, in association with herbal extract, contributed to a zeta potential value of -4.73 Mv. It was discovered that ELSN IC50 was 75.13 ± 3.29 μg/mL. Conclusion: This study confirms that the development of ELSN improves the poor water solu-bility and bioavailability of the drug as well as enhances the therapeutic efficacy.

Nanoemulsion potentiates the anti-cancer activity of Myricetin by effective inhibition of PI3K/AKT/mTOR pathway in triple-negative breast cancer cells.

Triple-negative breast cancer (TNBC) is a heterogeneous tumor with a poor prognosis and high metastatic potential, resulting in poor clinical outcomes, necessitating investigation to devise effective therapeutic strategies. Multiple studies have substantiated the anti-cancer properties of the naturally occurring flavonoid "Myricetin" in various malignancies. However, the therapeutic application of Myricetin is impeded by its poor water solubility and low oral bioavailability. To overcome this limitation, we aimed to develop nanoemulsion of Myricetin (Myr-NE) and evaluate its advantage over Myricetin alone in TNBC cells. The nanoemulsion was formulated using Capryol 90 (oil), Tween 20 (surfactant), and Transcutol HP (co-surfactant). The optimized nano-formulation underwent an evaluation to determine its size, zeta potential, morphology, stability, drug encapsulation efficiency, and in vitro release properties. The anti-cancer activity of Myr-NE was further studied to examine its distinct impact on intracellular drug uptake, cell-viability, anti-tumor signaling, oxidative stress, clonogenicity, and cell death, compared with Myricetin alone in MDA-MB-231 (TNBC) cells. The in vitro drug release and intracellular drug uptake of Myricetin was significantly increased in Myr-NE formulation as compared to Myricetin alone. Moreover, Myr-NE exhibited significant inhibition of cell proliferation, clonogenicity, and increased apoptosis with ~ 2.5-fold lower IC50 as compared to Myricetin. Mechanistic investigation revealed that nanoemulsion augmented the anti-cancer efficacy of Myricetin, most likely by inhibiting the PI3K/AKT/mTOR pathway, eventually leading to enhanced cell death in TNBC cells. The study provides substantial experimental evidence to support the notion that the Myr-NE formulation has the potential to be an effective therapeutic drug for TNBC treatment.

A Quality by Design Approach for Developing SNEDDS Loaded with Vemurafenib for Enhanced Oral Bioavailability.

Vemurafenib (VMF) is a practically insoluble (< 0.1μg/mL) and least bioavailable (1%) drug. To enhance its oral bioavailability and solubility, we formulated a reliable self-nano emulsifying drug delivery system (SNEDDS). A Quality by Design (QbD) approach was used to optimize the ratio of Capryol 90, Tween 80, and Transcutol HP. VMF-loaded SNEDDS was characterized for its size, polydispersity index (PDI), zeta potential, drug content, and transmittance. The in vitro release profile of the drug loaded in SNEDDS was compared to the free drug in two media, pH 6.8 and 1.2, and the data obtained were analyzed with different mathematical models. A reverse-phase ultra-pressure liquid chromatography (UPLC) technique with high sensitivity and selectivity was developed and validated for the quantification of VMF in analytical and bioanalytical samples. Dissolution efficiency for SNEDDS was estimated using different models, which proved that the developed novel SNEDDS formulation had a better in vitro dissolution profile than the free drug. A 2.13-fold enhanced oral bioavailability of VMF-loaded SNEDDS compared to the free drug demonstrates the superiority of the developed formulation. This work thus presents an overview of VMF-loaded SNEDDS as a promising alternative to improve the oral bioavailability of the drug.

Development, optimization, and characterization of rhein loaded nanoemulgel for treatment of osteoarthritis

This work aimed to design a transdermal delivery of rhein loaded nanoemulgel to improve the bioavailability and efficacy of rhein in the treatment of osteoarthritis and reduce its systemic side effects. Rhein loaded nanoemulsion (Rh-NE) prepared by application of ternary phase diagram and spontaneous emulsification method. Box-Behnken design (BBD) was employed to optimize formulation and preparation process of Rh-NE. The optimal formulation was 11.09% mixed oil (rhein and caproyl 90), 22.96% mixed emulsifier (kolliphor RH 40: transcutol HP, 1:1, w/w), and the preparation process was 23.08 min ultrasonic time and 179.5 W ultrasonic power. The particle size of the optimized Rh-NE was 24.5 ± 3.2 nm, PDI was 0.15 ± 0.02, and zeta potential was −18.6 ± 1.8 mV. The Rh-NE was incorporated into hydrogel consisted of 0.85% carbomer, 0.2% poloxamer 188 and 8.0% glycerol to form rhein loaded nanoemulgel (Rh-NE/Gel). In vitro transdermal flux of Rh-NE/Gel was 91.4 ± 0.9 μg/cm2·h. It was found that the inhibition rate of swelling degree of auricle caused by xylene was (54%), inhibition rate of writhing reaction was (60%), percentage increase in pain threshold was (P < 0.01), and the inhibition rate of capillary permeability was (69%). The therapeutic effect of Rh-NE/Gel on osteoarthritis in model rats was significantly improved compared with control group; the swelling degree of joint and toe were significantly reduced by 91% and 71%, respectively, and the contents of inflammatory factors IL-1β and NO were decreased 35.7% and 52.4%, respectively. The developed Rh-NE/Gel could provide anti-osteoarthritis effect and reduce the release of proinflammatory mediators in OA model rats.

Rosuvastatin-loaded solid SMEDDS: an innovative approach for solubility augmentation and improved pharmacodynamic profile

The objectives undertaken in current work were to develop a new solid self-microemulsifying drug delivery system (S-SMEDDS) for poorly water-soluble Rosuvastatin Calcium (RST) and evaluate its antihyperlipidemic activity in rodent model. Solubility assessment in variety of excipients, screening studies and optimization of pseudoternary plots helped in development of liquid SMEDDS. Liquid SMEDDS of RST contained Capryol 90, Kolliphor EL and Transcutol HP as oil phase, surfactant and co-surfactant respectively which were evaluated for release, self-emulsification ability, percentage transmittance and globule size. Florite RE was used as the adsorbent to transform the optimized liquid SMEDDS into non-coherent powder which was then examined for micromeritic properties, solid state characterization and in vitro dissolution studies. It was additionally investigated for antihyperlipidemic activity in rats subjected to high fat diet. Optimized liquid SMEDDS of RST was found to undergo a swift transformation in a microemulsion having globule size in nanometric size range with consistent size distribution. The liquid SMEDDS adsorbed on Florite RE exhibited favorable micromeritic properties and spherical shape. XRD studies indicated amorphization of RST due to its molecular dispersion in S-SMEDDS. Enhanced in vitro rate of dissolution of optimized formulation was observed in comparison to pure drug and commercial product. There was considerable reduction (p < 0.001) in serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDL-C), very low-density lipoproteins (VLDL-C) when S-SMEDDS was administered and increment in high-density lipoproteins (HDL-C) level compared to plain drug suspension. RST S-SMEDDS holds great potential for enhancement of its physiochemical along with biological attributes.

Self‐Emulsifying Drug Delivery of Khellin for Improving Its Oral Bioavailability

AbstractSelf‐emulsifying drug delivery system (SEDDS) is extensively used for enhancing the solubility, dissolution, and pharmacokinetics of poorly soluble drugs. Khellin is a natural product with multiple pharmacological activities and has inspired the discovery of two first‐in‐class drugs, amiodarone hydrochloride and sodium cromoglycate. The poor‐aqueous solubility is one of the limitations in developing this molecule. Herein, we aimed to improve the drug loading of khellin by developing its SEDDS formulation. A combination of castor oil, tetraethylene glycol, and Transcutol HP (10 : 30 : 60 v/v) was identified, inhibiting the drug‘s precipitation post‐dilution in an aqueous media. The optimized formulation, SB‐16KD, was characterized using 1H NMR, DSC, and FTIR to understand khellin‘s physical/chemical interaction with the formulation excipients. The in vitro dissolution studies of khellin in SB‐16KD correlated well with the oral pharmacokinetics in Wistar rats (1.6 vs. 1.7‐fold). The comparative oral pharmacokinetics of formulation against native khellin was performed at 45 mg/kg in Wistar rats. The results were promising, with 1.7‐fold higher plasma exposure by SEDDS formulation. Hence, the results warrant further developmental studies on SEDDS in dose reduction.

Natural microbial surfactant containing self-nanoemulsifying formulation with improved performance of paclitaxel therapy: A newer avenue in breast cancer treatment

Due to the presence of a high concentration of surfactants (e.g., Cremophor EL, Tween 80), paclitaxel (PTX) drug delivery systems administered orally and intravenously demonstrate severe toxicity. In the current research work, a unique self-nanoemulsifying drug delivery system (SNEDDS) comprising surfactin, a microbial biosurfactant was used for reducing the formulation toxicity and improving the biopharmaceutical performance. The preformulation study including solubility analysis indicated suitability of corn oil as the natural lipophile. Nanoemulsion boundaries were delineated by aqueous titration of the lipid phase (ethyl oleate: plurol oleique), surfactants (Tween 80 and Surfactin) and cosolvent (Transcutol HP) to identify the optimum compositions on the basis of formulation quality attributes with globule size <250 nm, emulsification time <3 min and in vitro drug release >85% in 60 min. Biocompatibility evaluation of PTX-Surfactin SNEDDS on rat hepatocytes by H2DCF assay to determine the ROS level indicated an insignificant increase in fluorescence intensity, while PTX Tween 80-SNEDDS showed nearly 20% increase in ROS levels compared to the control cells. Furthermore, histopathology examination showed the absence of any signs of inflammation from intestinal segments treated with PTX Surfactin-SNEDDS, while PTX Tween 80-SNEDDS revealed infiltration of cells and the presence of inflammation on the intestinal villous microstructures. The anticancer activity evaluation by in vitro cytotoxicity on MCF-7 cells showed PTX Surfactin-SNEDDS and PTX Tween 80-SNEDDS with IC50 of 2.65 μM and 11.52 μM, respectively, while PTX suspension showed IC50 of 18.5 μM. Moreover, blank Surfactin-SNEDDS showed IC50 of 15.23 μM, while no cytotoxicity was observed for blank Tween 80-SNEDDS. Overall, the study interpreted high suitability of biosurfactant for developing the self-nanoemulsifying formulation of PTX with enhanced bioavailability, biocompatibility and synergistic improvement in the anticancer activity over the formulations containing synthetic surfactant.

Aceclofenac/Citronellol Oil Nanoemulsion Repurposing Study: Formulation, In Vitro Characterization, and In Silico Evaluation of Their Antiproliferative and Pro-Apoptotic Activity against Melanoma Cell Line.

Aceclofenac (ACF) is a widely used non-steroidal anti-inflammatory drug (NSAID) known for its effectiveness in treating pain and inflammation. Recent studies have demonstrated that ACF possesses antiproliferative properties, inhibiting the growth of cancer cells in various cancer cell lines. Citronellol, a monoterpenoid alcohol found in essential oils, exhibits antioxidant properties and activities such as inhibiting cell growth and acetylcholinesterase inhibition. In this study, the objective was to formulate and evaluate an aceclofenac/citronellol oil nanoemulsion for its antiproliferative effects on melanoma. The optimal concentrations of citronellol oil, Tween 80, and Transcutol HP were determined using a pseudoternary phase diagram. The formulated nanoemulsions were characterized for droplet size, zeta potential, thermophysical stability, and in vitro release. The selected formula (F1) consisted of citronellol oil (1 gm%), Tween 80 (4 gm%), and Transcutol HP (1 gm%). F1 exhibited a spherical appearance with high drug content, small droplet size, and acceptable negative zeta potential. The amorphous state of the drug in the nanoemulsion was confirmed by Differential Scanning Calorimetry, while FTIR analysis indicated its homogenous solubility. The nanoemulsion showed significant antiproliferative activity, with a lower IC50 value compared to aceclofenac or citronellol alone. Flow cytometric analysis revealed cell cycle arrest and increased apoptosis induced by the nanoemulsion. In silico studies provided insights into the molecular mechanism underlying the observed antitumor activity. In conclusion, the developed aceclofenac/citronellol oil nanoemulsion exhibited potent cytotoxicity and pro-apoptotic effects, suggesting its potential as a repurposed antiproliferative agent for melanoma treatment. In a future plan, further animal model research for validation is suggested.

Nanoemulsion-Based Strategy for Maximizing Nitrofurantoin Absorption: In-vitro and In-vivo Investigations.

The main objective of the current research work is to improve the absorption of Nitrofurantoin (NFT) by minimizing gastrointestinal (GI) intolerance and variations in its absorption by formulating the drug into a nanoemulsion (NE). Based on the highest saturation solubility of NFT, soybean oil, transcutol HP, and labrafil M1944CS were selected as oil, co-surfactant, and surfactant, and a Smix ratio of 1:2 was selected based on pseudoternary phase diagrams. The formulation prepared with an equal ratio of oil and Smix exhibited the lowest globule size, highest zeta potential, and higher drug release and hence was selected for further evaluation. Optimized formulation (NF5) showed improved membrane permeability against pure drug suspension (2.30 times) and marketed suspension formulation (1.43 times). NF5 exhibited similar % cell viability and % cell toxicity in Caco-2 cell lines compared to the marketed suspension. The relative bioavailability of NFT-NE was enhanced by 1.10 and 1.17 times compared to the marketed and pure drug suspension, respectively. Thus, it can be concluded that the optimized nanoemulsion formulation of NFT exhibited improved membrane permeability, comparable cell viability, and increased relative bioavailability. These findings suggest the potential of the nanoemulsion approach as a strategy to overcome the variability of oral absorption and GI intolerance of NFT.

Omega-3 fatty acid-based self-microemulsifying drug delivery system (SMEDDS) of pioglitazone: Optimization, in vitro and in vivo studies

Pioglitazone (PGL) is an effective insulin sensitizer, however, side effects such as accumulation of subcutaneous fat, edema, and weight gain as well as poor oral bioavailability limit its therapeutic potential for oral delivery. Recent studies have shown that combination of both, PGL and fish oil significantly reduce fasting plasma glucose,improve insulin resistance, and mitigate pioglitazone-induced subcutaneous fat accumulation and weight gain. Nevertheless, developing an effective oral drug delivery system for administration of both medications have not been explored yet. Thus, this study aimed to develop a self-micro emulsifying drug delivery system (SMEDDS) for the simultaneous oral administration of PGL and fish oil. SMEDDS was developed using concentrated fish oil,Tween® 80, and Transcutol HP and optimized by central composite design (CCD). The reconstituted, optimized PGL-SMEDDS exhibited a globule size of 142 nm, a PDI of 0.232, and a zeta potential of −20.9 mV. The in-vitro drug release study of the PGL-SMEDDS showed a first-order model kinetic release and demonstrated remarkable 15-fold enhancement compared to PGL suspension. Additionally, following oral administration in fasting albino Wistar rats, PGL-SMEDDS exhibited 3.4-fold and 1.4-fold enhancements in the AUC0–24h compared to PGL suspension and PGL marketed product. The accelerated stability testing showed that the optimized SMEDDS formulation was stable over a three-month storage period. Taken together, our findings demonstrate that the developed fish oil-based SMEDDS for PGL could serve as effective nanoplatforms for the oral delivery of PGL, warranting future studies to explore its synergistic therapeutic potential in rats.

Design and Evaluation of Hydrophobic Ion Paired Insulin Loaded Self Micro-Emulsifying Drug Delivery System for Oral Delivery.

Despite several novel and innovative approaches, clinical translation of oral insulin delivery into commercially viable treatment is still challenging due to its poor absorption and rapid degradation in GIT. Thus, an insulin-SDS hydrophobic ion pair loaded self-microemulsifying drug delivery system (SMEDDS) was formulated to exploit the hypoglycemic effects of orally delivered insulin. Insulin was initially hydrophobically ion paired with sodium dodecyl sulphate (SDS) to enhance its lipophilicity. The successful complexation of Insulin-SDS was confirmed by FTIR and surface morphology was evaluated using SEM. Stability of insulin after its release from HIP complex was evaluated using SDS PAGE. Subsequently, Ins-SDS loaded SMEDDS was optimized using two factorial designs. In vitro stability of insulin entrapped in optimized SMEDDS against proteolytic degradation was also assessed. Further, antidiabetic activity of optimized Ins-SDS loaded SMEDDS was evaluated in diabetic rats. Insulin complexed with SDS at 6:1 (SDS/insulin) molar ratio with almost five-fold increased lipophilicity. The SMEDDS was optimized at 10% Labraphil M2125 CS, 70% Cremophore EL, and 20% Transcutol HP with better proteolytic stability and oral antidiabetic activity. An Ins-SDS loaded SMEDDS was successfully optimized. Compared with insulin and Ins-SDS complex, the optimized SMEDDS displayed considerable resistance to GI enzymes. Thus, the SMEDDS showed potential for effective delivery of macromolecular drugs with improved oral bioavailability.