Unlocking the Therapeutic Potential of Piperine- From Ethnopharmacology to Nanodelivery Strategies

This review article aims to develop nanotechnology in novel drug delivery systems using self-nano emulsifying drug delivery systems (SNEDDS). This Article was selected using a database with Prism Guideline diagrams. A total of 18 articles obtained from 2010-2020 were used as the primary reference to be analyzed using a systematic review method in the form of meta-synthesis. This review describes the mechanism of SNEDDS in increasing absorption, the components of the SNEDDS formula, the characterization of self-nano emulsifying drug delivery systems (SNEDDS), the effect of the physicochemical properties of SNEDDS on in vivo activity, and the basis for selecting compounds in the SNEDDS formulation. Self-Nanoemulsifying Drug Delivery System (SNEDDS) is a novel drug delivery system from nanoemulsion used to increase the solubility of lipophilic drugs. SNEDDS is an isotropic mixture consisting of oil, surfactant, and co-surfactant. SNEDDS is considered pre-concentrated nanoemulsions or anhydrous forms of nanoemulsions. In SNEDDS, the formation of nanoemulsions occurs when self-nanoemulsions come into contact with gastrointestinal fluids in the presence of light stirring in the peristaltic motion of the gastrointestinal tract. In general, SNEDDS have small particle sizes in the range of 10-200 nm. The application of the self nanoemulsion development system can be used for BCS Class II lipophilic drug compounds and BCS Class IV drugs. SNEDDS is a novel drug delivery system that can be used for oral drug delivery. In occlusion, a self-nanoemulsifying drug delivery system (SNEDDS) is a new approach for the formulation of drug molecules with poor water solubility. Self Nanoemulsifying drug delivery system (SNEDDS) is an isotropic mixture of oil, surfactant, and co-surfactant.

It was the aim of this study to evaluate the impact of lipases on the release behaviour of a peptide drug from oral self-nanoemulsifying drug delivery systems. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate, oleate and dodecylsulphate. The lipophilic character of these complexes was characterised by determining the n-octanol/buffer pH 7.4 partition coefficient. In the following the most hydrophilic complex was incorporated in a likely lipase degradable self-nanoemulsifying drug delivery systems (SNEDDS) formulation containing a triglyceride (olive oil; Pharm.Eur.) and in a likely not lipase degradable SNEDDS containing lipids and surfactants without any ester bonds. After 1:100 dilutions in artificial intestinal fluid (AIF), the lipid droplets were characterised regarding size distribution. With these SNEDDS, drug release studies were performed in AIF with and without lipase. Results showed that the most hydrophobic complex can be formed with deoxycholate in an octreotide:anionic surfactant ratio of 1:5. Even 73.1 ± 8.1% of it could be quantified in the n-octanol phase. SNEDDS containing octreotide | olive oil | cremophor EL | propylene glycol (2|57|38|3) and octreotide | liquid paraffin | Brij 35 | propylene glycol | ethanol (2|66.5|25|5|1.5) showed after dilution in AIF, a mean droplet size of 232 ± 53 nm and 235 ± 50 nm, respectively. Drug release studies showed a sustained release of octreotide out of these formulations for at least 24 h, whereas > 80% of the drug was released within 2 h in the presence of lipase in the case of the triglyceride containing SNEEDS. In contrast the release profile from ester-free SNEDDS was not significantly altered (p < 0.05) due to the addition of lipase providing evidence for the stability of this formulation towards lipases. According to these results, SNEDDS could be identified as a useful tool for sustained oral peptide delivery taking an enzymatic degradation by intestinal lipases into considerations.

Flavonoids, a diverse group of polyphenolic compounds found abundantly in fruits, vegetables, and medicinal plants, are renowned for their wide-ranging health benefits and therapeutic potential. Among them, myricetin, a naturally occurring flavonol, has emerged as a bioactive compound of significant pharmacological interest. This review provides a consolidated overview of myricetin, beginning with its methods of isolation from various plant sources, such as Diospyros kaki, Myrica rubra, and Rosa canina, and a detailed account of its in vitro and in vivo pharmacological activities, including its antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer, hepatoprotective, cardioprotective, and neuroprotective effects. Despite its promising bioactivities, the poor physicochemical properties of myricetin, such as its low aqueous solubility, stability, and limited bioavailability, pose substantial barriers to its clinical application. To address these challenges, this review highlights recent advancements in nanoformulation strategies, such as liposomes, solid lipid nanoparticles, nanofibers, nanostructured lipid carriers, polymeric nanoparticles, nanogels, micelles, and self-nanoemulsifying drug delivery systems, that enhance the pharmacokinetic profile and therapeutic efficacy of these methods. Furthermore, toxicological evaluations are discussed to assess its safety, supported by findings from preclinical studies. Additionally, the review summarizes the current status of clinical trials and highlights recent advancements in intellectual property through an analysis of granted patents related to myricetin. Notably, there is currently no review that comprehensively integrates all these aspects of myricetin. This study seeks to address this void by providing a unified and current perspective on the progression of myricetin from being a natural bioactive compound to being a viable candidate for therapeutic development.

Objective: Cancer is the deadliest disease affecting the life of the people all around the world. Colon cancer is the cancer which is affecting the colon region it is the last part of the gastrointestinal tract which is mainly responsible for the absorption of water and minerals from the food debris. Colon cancer is the second most cancer creating death in the world. It affects both male and female equally. Curcumin is a flavonoid used from decades for the treatment of various ailments including cancer. This present work is to formulate Self-nanoemulsifying drug delivery (SNEDDS) system with the help of curcumin for colon delivery.&#x0D; Materials and Methods: Nanoemulsion was prepared using the curcumin pre-concentrated self-nanoemulsifying drug delivery system, with which tablets were prepared and coated with pectin followed by the evaluation test such as in vitro dissolution and cell line studies.&#x0D; Results: Solubility profile of curcumin was found with a greater impact using Capmul MCM and Labrafac PG which is then added with the surfactants and co-surfactants and were converted into Nano-droplets. F1 formulation was selected after carrying out the characterisation studies and converted into a tablet dosage form and then coated with pectin, in vitro studies depicted a release of 80% in pH 6.8.&#x0D; Conclusions: Formulation of a solid self-Nano emulsifying drug delivery system using curcumin was successfully carried out. From the results obtained, the formulation (F1) was selected for the formation of the tablets and the further experimental part is carried out. The tablet dosage form is then coated with pectin and used for targeting the colon cancer cells for its treatment.

Self nano-emulsifying system drug delivery system (SNEDDS) is promising for drugs of BCS class II. The objective of present study to develop self nano-emulsifying drug delivery system for Lipophillic drug Telmisartan (TEL) to enhance the oral bioavailability of poorly water-soluble drug. TEL is an angiotensin II receptor blocker (ARB) and antihypertensive drug. Screening of Surfactant, Co-surfactant is done by percent transmittance and is also observed for turbidity or phase separation visually. Pseudo ternary phase diagram are constructed to identify the self-emulsifying regions and also to establish the optimum concentration of oil, surfactant and co-surfactant. For prepared formulation further characterization studies are done. Various studies like FTIR, SEM, Particle size, zeta potential is carried out for prepared SNEDDS. Further they are formulated into tablets and evaluated. All the results obtained are found to be in limits. From the present study it is clear that SNEDDS can be formulated to improve the dissolution and oral bioavailability of poorly water-soluble drug Telmisartan. Keywords: Bioavailability; poor water solubility; self-nanoemulsifying drug delivery system; telmisartan.

Self-nano-emulsifying drug delivery systems (SNEDDS) have gained attention in recent years as an effective approach for improving the solubility and oral bioavailability of poorly water-soluble drugs. However, there have been reports of drawbacks such as low drug loading, limited stability and variability in absorption. Various technologies have been investigated in conjunction with SNEDDS to alleviate such issues such as polymers being used to improve stability and drug loading; phospholipid complexes used to improve absorption and reduce inter and intrasubject variability; SNEDDS for drug targeting improves the targeting of drugs to specific site reducing the dosage required for action. 3D printing is used to create personalized and precise dosages; supersaturated SNEDDS is used to increase drug concentration; and solid SNEDDS are used to improve storage stability and patient compliance. The amalgamation of SNEDDS with these technologies has demonstrated promising results with regard to the improvement of medication delivery and has control over SNEDDS limitations. The present review elucidates the application of blended technologies with SNEDDS and the future potential for such drug delivery.

Formulation and evaluation of hyaluronic acid-based mucoadhesive self nanoemulsifying drug delivery system (SNEDDS) of tamoxifen for targeting breast cancer

This article describes current strategies to enhance aqueous solubility and dissolution rate of poor soluble drugs. Most drugs in the market are lipophilic with low or poor water solubility. There are various methods to enhance solubility: co-solvency, particle size reduction, salt formation and Self Nanoemulsifying drug delivery systems, SEDDS is a novel approach to enhance solubility, dissolution rate and bioavailability of drugs. The study involves formulation and evaluation of solid self-Nano emulsifying drug delivery system (S-SNEDDS) to enhance aqueous solubility and dissolution rate. Oral route is the most convenient route for non-invasive administration. S-SNEDDS has more advantages when compared to the liquid self-emulsifying drug delivery system. Excipients were selected depends upon the drug compatibility oils, surfactants and co surfactants were selected to formulate Liquid SNEDDS these formulated liquid self-nano emulsifying drug delivery system converted into solid by the help of porous carriers, Melted binder or with the help of drying process. Conversion process of liquid to solid involves various techniques; they are spray drying; freeze drying and fluid bed coating technique; extrusion, melting granulation technique. Liquid SNEDDS has a high ability to improve dissolution and solubility of drugs but it also has disadvantages like incompatibility, decreased drug loading, shorter shelf life, ease of manufacturing and ability to deliver peptides that are prone to enzymatic hydrolysis.&#x0D;

Single garlic has been known have various benefits because it contains many active compounds. The active compounds in garlic, like antioxidants are quickly degraded in the digestive tract. Various attempts have been made to maintain the antioxidants content in garlic through drug delivery systems. One of the drug delivery systems that can protect antioxidants is the Self Nanoemulsifying Drug Delivery System (SNEDDS). This study aims to characterize and test the antioxidant activity of SNEDDS single garlic extract (SGE). The methods used include single garlic extraction with ethanol solvent, SNEDDS formulation, SNEDDS preparation, SNEDDS response test, and physical tests. Characterization of SNEDDS size and morphology using Particle Size Analyzer (PSA) and Transmission Electron Microscopy (TEM). An antioxidant activity test was carried out using the DPPH method. The results showed that the mean droplet size of SNEDDS-SGE was 23.10±0.69 nm, the polydispersity index (PDl) was 0,46±0,01 and the Zeta potential was -33.07±0.45 mV. The morphology of SNEDDS is a round droplet. The results of the antioxidant activity test showed that the percentage of antioxidant activity of SNEDDS-SGE was 56.74±1,04 which was higher than the percentage of antioxidant activity of SGE that was not prepared with SNEDDS 17.56 ±0.08.

&#x0D; Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble drugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yielding micro or nanoemulsions containing the solubilized drug. The objective of the present work was to formulate a self nanoemulsifying drug delivery system (SNEDDS) for naproxen. Naproxen SNEDDS were formulated using Labrafac PG (Oil), Span 80 (Surfactant) and propylene glycol (Co surfactant). The developed SNEDDS were evaluated for turbidimetry, droplet size analysis, zeta potential, refractive index, viscosity, drug content and in vitro diffusion profiles. All formulations of naproxen SNEDDS showed globule size in nanometric range, good stability with no phase separation and rapidly formed clear emulsion. All formulations showed more than 95% of drug release at the end of 60 min. The SEDDS showed improved dissolution rate compared to pure naproxen. Anti-inflammatory studies were conducted in Wistar strain male albino rats and ibuprofen SNEDDS showed more significant activity than the pure drug. The study illustrated the potential of naproxen SNEDDS for oral administration and its biopharmaceutical performance.

Self-nanoemulsifying drug delivery systems (SNEDDS) for oral delivery of protein drugs: II. In vitro transport study

To formulate and characterize tablets containing Pitavastatin that have been loaded with a self-nano emulsifying drug delivery system (SNEDDS). Pitavastatin SNEDDS were prepared with a variety of oils, surfactants, co-surfactants, and solvents to improve the dissolution rate and bioavailability of the HMG-CoA reductase inhibitor. The SNEDDS components were preliminarily investigated for drug solubility in various vehicles, excipient miscibility, emulsification rate, and ternary phase diagrams. The tablets were made using a porous carrier made of Aerosil 200 and then loaded with SNEDDS using a simple absorption method. Physical parameters such as tablet hardness, weight variation, disintegration, drug content, and in-vitro drug release were then measured on the tablets. Labrafac Lipophilewl1349 (Oil), Tween 80 (Surfactant) and Egg lecithin (Co-surfactant) were selected for the preparation of SNEDDS. Tablets with high porosity suitable for loading with SNEDDS and containing the super-disintegrants, achieved complete dissolution of Pitavastatin from the tablets. In vitro release of Pitavastatin from SNEDDS and the tablets was similar (p < 0.05). SNEDDS of Pitavastatin is a promising approach to achieving a solid dosage form of the liquid-loaded drug delivery systems for enhancing the solubility and dissolution rate of the drug, and hence also its bioavailability.

Single bulb garlic (SBG) has the potential as an immunomodulator; however, it has low solubility and bioavailability. A lipid-based delivery system, that is, the self-nanoemulsifying drug delivery system (SNEDDS), offers a novel opportunity in drug delivery. SBG can be a suitable candidate for SNEDDS development. This research aims to describe the physical stability, toxicity test of the SNEDDS, and SNEDDS SBG potential as antiinflammation in 3T3-L1 cells. The SNEDDS is made with various ratios of concentrations of carrier oil, surfactants, and cosurfactants, namely, 0.50: 3.45: 0.96, and added with SBG extract (SBGE) of 20 mg/mL. The results of the response test of SNEDDS SBGE formulation indicate an average and standard deviation of emulsification time of 16.38±3.01 (second), pH 7.21±0.08, and transmittance of 98.40±0.23(%). The average nanoemulsion size is 14.333±0.416 nm, polydispersion index of 0.213±0.056, and zeta potential of -14.67±0.72 mV. The results of the physical stability test indicate no segregation, deposition, cracking, or creaming in all nanoemulsion samples and SNEDDS SBG. The MTT test in a dose of 62.5, 125, 250, 500, 100, 2000, and 4000 µg/mL suggests that the highest viability of the 3T3-L1 cells is at a dose of 2000 µg/mL, which is 97.83%±1.55%. Therefore, SNEDDS SBGE can be a potential candidate for oral preparation by increasing bioavailability and reducing toxicity in the 3T3-L1 cells. An antiinflammatory test on the TNF-𝛼 and IL-1𝛽 expressions influences the 3T3-L1 cells. the SNEDDS of SBGE has the potential to reduce the expression of TNF-𝛼 and IL-1𝛽 and increase IL-10 expression in the methylglyoxal-induced 3T3-L1 cells.

Chapter 12 - Self-nanoemulsifying drug delivery systems (SNEDDS) and self-microemulsifying drug delivery systems (SMEDDS) as lipid nanocarriers for improving dissolution rate and bioavailability of poorly soluble drugs

Particulate delivery system can be used for improving the efficacy of protein and peptide drug. In addition to a polymer-based particulate delivery system, self-nanoemulsifying drug delivery system (SNEDDS), a lipid-based delivery system, is currently developed for either less water-soluble or soluble drugs. This study aims to design SNEDDS for oral insulin administration and its in vitro-in vivo study. The SNEDDS template was designed using D-optimal mixture design and was analyzed using software Design Expert 7.1.5. The obtained optimum template was loaded with insulin and evaluated for its transmittance percentage, emulsification time, particle size, zeta potential, stability, the amount of insulin in vitro diffused across rat intestine, and insulin serum concentration after oral administration. The study results revealed that the optimum template of SNEDDS formula consisted of 10% (w/w) Miglyol 812N, 65% (w/w) Tween 80, and 25% (w/w) propylene glycol. These optimum template then was loaded with insulin and characterized. SNEDDS insulin has particle size of 12.0±1.7 nm, zeta potential of +0.16mV, transmittance of >90%, and emulsification time of < 60 seconds. The stability study showed that SNEDDS insulin was stable from both precipitation and phase separation. The amount of insulin transported from SNEDDS formula in vitro was 32.45±2.03% and non-SNEDDS formula was 10.44±5.04%. In vivo study of SNEDDS insulin produced a significantly increased Cmax, AUC, and F value than insulin non SNEDDS (p < 0.05). In brief, SNEDDS formulation in this study is a promising approach to increase the effectiveness of oral insulin. Insulin is better given orally in SNEDDS formulation than in non SNEDDS formulation.