Synthetic extremophiles via species-specific formulations improve microbial therapeutics.

Microorganisms typically used to produce food and pharmaceuticals are now being explored as medicines and agricultural supplements. However, maintaining high viability from manufacturing until use remains an important challenge, requiring sophisticated cold chains and packaging. Here we report synthetic extremophiles of industrially relevant gram-negative bacteria (Escherichia coli Nissle 1917, Ensifer meliloti), gram-positive bacteria (Lactobacillus plantarum) and yeast (Saccharomyces boulardii). We develop a high-throughput pipeline to define species-specific materials that enable survival through drying, elevated temperatures, organic solvents and ionizing radiation. Using this pipeline, we enhance the stability of E. coli Nissle 1917 by more than four orders of magnitude over commercial formulations and demonstrate its capacity to remain viable while undergoing tableting and pharmaceutical processing. We further show, in live animals and plants, that synthetic extremophiles remain functional against enteric pathogens and as nitrogen-fixing plant supplements even after exposure to elevated temperatures. This synthetic, material-based stabilization enhances our capacity to apply microorganisms in extreme environments on Earth and potentially during exploratory space travel.

Drinkable in situ-forming tough hydrogels for gastrointestinal therapeutics.

Pills are a cornerstone of medicine but can be challenging to swallow. While liquid formulations are easier to ingest, they lack the capacity to localize therapeutics with excipients nor act as controlled release devices. Here we describe drug formulations based on liquid in situ-forming tough (LIFT) hydrogels that bridge the advantages of solid and liquid dosage forms. LIFT hydrogels form directly in the stomach through sequential ingestion of a crosslinker solution of calcium and dithiol crosslinkers, followed by a drug-containing polymer solution of alginate and four-arm poly(ethylene glycol)-maleimide. We show that LIFT hydrogels robustly form in the stomachs of live rats and pigs, and are mechanically tough, biocompatible and safely cleared after 24 h. LIFT hydrogels deliver a total drug dose comparable to unencapsulated drug in a controlled manner, and protect encapsulated therapeutic enzymes and bacteria from gastric acid-mediated deactivation. Overall, LIFT hydrogels may expand access to advanced therapeutics for patients with difficulty swallowing.

In vitro and in silico computational methods for assessing vaginal permeability.

OBJECTIVE: Vaginal administration is an important alternative to the oral route for both topical and systemic use. Therefore, the development of reliable in silico methods for the study of drugs permeability is becoming popular in order to avoid time-consuming and costly experiments. METHODS: In the current study, Franz cells and appropriate HPLC or ESI-Q/MS analytical methods were used to experimentally measure the apparent permeability coefficient (Papp) of 108 compounds (drugs and non-drugs). Papp values were then correlate with 75 molecular descriptors (physicochemical, structural, and pharmacokinetic) by developing two Quantitative Structure Permeability Relationship (QSPR) models, a Partial Least Square (PLS) and a Support Vector Machine (SVM). Both were validated by internal, external and cross-validation. RESULTS: Based on the calculated statistical parameters (PLS model A: R2 = 0.673 and Q2 = 0.594, PLS model B: R2 = 0.902 and Q2 = 0.631, SVM: R2 = 0.708 and Q2 = 0.758). SVM presents higher predictability while PLS adequately interprets the theory of permeability. CONCLUSIONS: The most important parameters for vaginal permeability were found to be the relative PSA, logP, logD, water solubility and fraction unbound (FU). Respectively, the combination of both models could be a useful tool for understanding and predicting the vaginal permeability of drug candidates.

In Situ Gelling Electrospun Ocular Films Sustain the Intraocular Pressure-Lowering Effect of Timolol Maleate: In Vitro, Ex Vivo, and Pharmacodynamic Assessment.

Most common intraocular pressure (IOP) reduction regimens for the management of glaucoma include the topical use of eye drops, a dosage form that is associated with short residence time at the site of action, increased dosing frequency, and reduced patient compliance. In situ gelling nanofiber films comprising poly(vinyl alcohol) and Poloxamer 407 were fabricated via electrospinning for the ocular delivery of timolol maleate (TM), aiming to sustain the IOP-lowering effect of the ß-blocker, compared to conventional eye drops. The electrospinning process was optimized, and the physicochemical properties of the developed formulations were thoroughly investigated. The fiber diameters of the drug-loaded films ranged between 123 and 145 nm and the drug content between 5.85 and 7.83% w/w. Total in vitro drug release from the ocular films was attained within 15 min following first-order kinetics, showing higher apparent permeability (Papp) values across porcine corneas compared to the drug's solution. The fabricated films did not induce any ocular irritation as evidenced by both the hen's egg test on chorioallantoic membrane and the in vivo Draize test. In vivo administration of the ocular films in rabbits induced a faster onset of action and a sustained IOP-lowering effect up to 24 h compared to TM solution, suggesting that the proposed ocular films are promising systems for the sustained topical delivery of TM.

A simple and green liquid chromatography method for the determination of ibuprofen in milk-containing simulated gastrointestinal media for monitoring the dissolution studies of three-dimensional-printed formulations.

A fast and green ultra-high-performance liquid chromatographic method was developed for the determination of ibuprofen in milk-containing simulated gastrointestinal media to monitor the dissolution of three-dimensional printed formulations. To remove interfering compounds, protein precipitation using methanol as a precipitation reagent was performed. The separation of the target analyte was performed on a C18 column using a mobile phase consisting of 0.05% v/v aqueous phosphoric acid solution: methanol, 25:75% v/v. Method validation was conducted using the total error concept. The ß-expectation tolerance intervals did not exceed the acceptance criteria of ±15%, meaning that 95% of future results will be included in the defined bias limits. The relative bias ranged between ─1.1 and +3.2% for all analytes, while the relative standard deviation values for repeatability and intermediate precision were less than 2.8% and 3.9%, respectively. The achieved limit of detection was 0.01 µg/ml and the lower limit of quantitation was established as 2 µg/ml. The proposed method was simple, and it required reduced organic solvent consumption following the requirements of Green Analytical Chemistry. The method was successfully employed for the determination of ibuprofen in real biorelevant media obtained from dissolution studies.

Partial Least Square Model (PLS) as a Tool to Predict the Diffusion of Steroids Across Artificial Membranes.

One of the most challenging goals in modern pharmaceutical research is to develop models that can predict drugs' behavior, particularly permeability in human tissues. Since the permeability is closely related to the molecular properties, numerous characteristics are necessary in order to develop a reliable predictive tool. The present study attempts to decode the permeability by correlating the apparent permeability coefficient (Papp) of 33 steroids with their properties (physicochemical and structural). The Papp of the molecules was determined by in vitro experiments and the results were plotted as Y variable on a Partial Least Squares (PLS) model, while 37 pharmacokinetic and structural properties were used as X descriptors. The developed model was subjected to internal validation and it tends to be robust with good predictive potential (R2Y = 0.902, RMSEE = 0.00265379, Q2Y = 0.722, RMSEP = 0.0077). Based on the results specific properties (logS, logP, logD, PSA and VDss) were proved to be more important than others in terms of drugs Papp. The models can be utilized to predict the permeability of a new candidate drug avoiding needless animal experiments, as well as time and material consuming experiments.

Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Rice Bran Oil for Enhanced Fenofibrate Oral Delivery: In Vitro Digestion, Ex Vivo Permeability, and In Vivo Bioavailability Studies.

Lipid-based drug delivery systems (LbDDS), such as self-nanoemulsifying drug delivery systems (SNEDDS), constitute a prominent formulation approach for enhancing the aqueous solubility and oral bioavailability of poorly water-soluble compounds. Utilization of biorefinery wastes, such as oil from rice bran, may prove advantageous to both improving drug solubilization and absorption and to achieving sustainable agri-food waste valorization. Here, we assessed the effect of four SNEDDS compositions differing in the oil (rice bran oil and corn oil) and surfactant type (Kolliphor RH40 and EL) on the oral bioavailability of fenofibrate, a BCS class II compound. Prior to the in vivo oral administration of the SNEDDS in rats, drug solubilization was tested in vitro using the static digestion model, followed by the ex vivo permeability study of the predigested SNEDDS using the non-everted gut sac model. No significant variation was observed in the solubilization capacity within the different SNEDDS formulations. On the other hand, the ex vivo permeability data of the predigested SNEDDS correlated well with the in vivo bioavailability data designating the superiority of rice bran oil with Kolliphor EL as the surfactant, to enhance the oral absorption of fenofibrate. Results indicated that valorization of agro-industrial waste such as rice bran oil may prove useful in enhancing the oral performance of LbDDS in the case of fenofibrate, while at the same time maximizing the use of agricultural by-products via the creation of new sustainable value chains in the pharmaceutical field.

Synergistic Antitumor Potency of a Self-Assembling Peptide Hydrogel for the Local Co-delivery of Doxorubicin and Curcumin in the Treatment of Head and Neck Cancer.

Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve a sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin and curcumin was assessed against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug's aqueous solubility. A significantly enhanced cell growth inhibitory effect was observed after treatment with the combination drug-loaded hydrogel formulations compared to the respective combination drug solution. The synergistic pharmacological effect of selected hydrogel formulations was further confirmed with enhanced apoptotic cell response, interference in cell cycle progression, and significantly altered apoptotic/anti-apoptotic gene expression profiles obtained in dose levels well below the half-maximal inhibitory concentrations of both drugs. The in vivo antitumor efficacy of the drug-loaded peptide hydrogel formulation was confirmed in HSC-3 cell-xenografted severe combined immunodeficient mice and visualized with µCT imaging. Histological and terminal deoxynucleotidyl transferase dUTP nick end labeling assay analyses of major organs were implemented to assess the safety of the topically administered hydrogel formulation. Overall, results demonstrated the therapeutic utility of the dual drug-loaded peptide hydrogel as a pertinent approach for the local treatment of head and neck cancer.

Development and Characterization of a Self-Nanoemulsifying Drug Delivery System Comprised of Rice Bran Oil for Poorly Soluble Drugs.

Poor aqueous solubility and low bioavailability are limiting factors in the oral delivery of lipophilic drugs. In a formulation approach to overcome these limitations, rice bran (RB) oil was evaluated as drug carrier in the development of self-nanoemulsifying drug delivery systems (SNEDDS). The performance of RB in formulations incorporating Kolliphor RH40 or Kolliphor EL as surfactants and Transcutol HP as cosolvent was compared to a common oil vehicle, corn oil (CO). Serial dilutions of the preconcentrates were performed in various media [distilled water and simulated intestinal fluids mimicking fasted state (FaSSIF) and fed state (FeSSIF)] and at different dilution ratios to simulate the in vivo droplets' behavior. The developed SNEDDS were assessed by means of phase separation, droplet size, polydispersity index, and ζ-potential. Complex ternary diagrams were constructed to identify compositions exhibiting monophasic behavior, droplet size < 100 nm, and polydispersity index (PDI) < 0.25. Multifactor analysis and response surface areas intended to determine the factors significantly affecting droplet size. The oil capacity to accommodate lipophilic drugs was assessed via fluorescence spectroscopy based on the solvatochromic behavior of Nile Red. Solubility studies were performed to prepare fenofibrate- and itraconazole-loaded SNEDDS and assess their droplet size, whereas dissolution experiments were conducted in simulated intestinal fluids. Caco-2 cell viability studies confirmed the safety of the SNEDDS formulations at 1:100 and 1:1000 dilutions after cell exposure in culture for 4 h. The obtained results showed similar performance between RB and CO supporting the potential of RB as oil vehicle for the effective oral delivery of lipophilic compounds.

Chemotherapeutic Delivery from a Self-Assembling Peptide Nanofiber Hydrogel for the Management of Glioblastoma.

PURPOSE: Localized chemotherapy has gained significant impetus for the management of malignant brain tumors. In the present study, we appraised the versatility of an in-situ gel forming self-assembling peptide, ac-(RADA)4-CONH2, as a biocompatible delivery depot of the chemotherapeutic drug doxorubicin (DOX) and the anticancer agent curcumin (CUR), respectively. METHODS: The morphology and mechanical properties of ac-(RADA)4-CONH2 were assessed with scanning electron microscopy (SEM) and rheological studies. The in vitro drug release from ac-(RADA)4-CONH2 was monitored in phosphate-buffered saline pH 7.4. Distribution of the fluorescent actives within the peptide matrix was visualized with confocal laser scanning microscopy (CLSM). The in vitro biological performance of the ac-(RADA)4-CONH2-DOX and ac-(RADA)4-CONH2-CUR was evaluated on the human glioblastoma U-87 MG cell line. RESULTS: SEM studies revealed that the ac-(RADA)4-CONH2 hydrogel contains an entangled nanofiber network. Rheology studies showed that the more hydrophobic CUR resulted in a stiffer hydrogel compared with ac-(RADA)4-CONH2 and ac-(RADA)4-CONH2-DOX, due to the interaction of CUR with the hydrophobic domains of the peptide nanofibers as confirmed by CLSM. In vitro release studies showed a complete DOX release from ac-(RADA)4-CONH2 within 4 days and a prolonged release for ac-(RADA)4-CONH2-CUR over 20 days. An increased cellular uptake and a higher cytotoxic effect were observed for ac-(RADA)4-CONH2-DOX, compared with DOX solution. Higher levels of early apoptosis were observed for the cells treated with the ac-(RADA)4-CONH2-CUR, compared to CUR solution. CONCLUSIONS: The current findings highlight the potential utility of the in-situ depot forming ac-(RADA)4-CONH2 hydrogel for the local delivery of both water soluble and insoluble chemotherapeutic drugs.

Controlled Release of 5-Fluorouracil from Alginate Beads Encapsulated in 3D Printed pH-Responsive Solid Dosage Forms.

Three-dimensional printing is being steadily deployed as manufacturing technology for the development of personalized pharmaceutical dosage forms. In the present study, we developed a hollow pH-responsive 3D printed tablet encapsulating drug loaded non-coated and chitosan-coated alginate beads for the targeted colonic delivery of 5-fluorouracil (5-FU). A mixture of Eudragit® L100-55 and Eudragit® S100 was fabricated by means of hot-melt extrusion (HME) and the produced filaments were printed utilizing a fused deposition modeling (FDM) 3D printer to form the pH-responsive layer of the tablet with the rest comprising of a water-insoluble poly-lactic acid (PLA) layer. The filaments and alginate particles were characterized for their physicochemical properties (thermogravimetric analysis, differential scanning calorimetry, X-ray diffraction), their surface topography was visualized by scanning electron microscopy and the filaments' mechanical properties were assessed by instrumented indentation testing and tensile testing. The optimized filament formulation was 3D printed and the structural integrity of the hollow tablet in increasing pH media (pH 1.2 to pH 7.4) was assessed by means of time-lapsed microfocus computed tomography (µCT). In vitro release studies demonstrated controlled release of 5-FU from the alginate beads encapsulated within the hollow pH-sensitive tablet matrix at pH values corresponding to the colonic environment (pH 7.4). The present study highlights the potential of additive manufacturing in fabricating controlled-release dosage forms rendering them pertinent formulations for further in vivo evaluation.

Preparation and characterization of bioadhesive microparticles comprised of low degree of quaternization trimethylated chitosan for nasal administration: effect of concentration and molecular weight.

Toward the development of microparticulate carriers for nasal administration, N-trimethylchitosan chloride (TMC) of low molecular weight (LMW) and high molecular weight (HMW) and low degree of quaternization (16% and 27%, respectively) was co-formulated into microparticles comprising of dipalmatoylphosphatidylcholine (DPPC) and poly(lactic-co-glycolic) acid (PLGA) via the spray-drying technique. The chitosan derivatives were characterized by means of nuclear magnetic resonance (NMR), differential scanning calorimetry (DSC), and Fourier transfrom infrared (FTIR) spectroscopy. The size and morphology of the produced microparticles were assessed by scanning electron microscopy (SEM), whereas their mucoadhesive properties were investigated by means of atomic force microscopy-force spectroscopy (AFM-FS). The results showed that microparticles exhibit mucoadhesion when TMC is present on their surface above a threshold of TMC (>0.3% w/w).

Analytical QbD for the optimization of a multimode HPLC method for the investigation of hydrochlorothiazide, diltiazem and propranolol release from 3D printed formulation.

Since 3D printing technology is an emerging field in pharmaceutical technology, the present study aimed at the development of a mixed-mode liquid chromatographic method for the separation and determination of hydrochlorothiazide, diltiazem, and propranolol to investigate their in-vitro release performance from 3D printed tablets. Due to the unique properties of the mixed-mode stationary phase, the three drugs were separated in less than 8 min under isocratic elution. Method development was accomplished following the Analytical Quality by Design principles and was evaluated using risk assessment and multivariate analysis. The influences of critical method parameters on critical method attributes (were screened using a 2-level fractional factorial design and subsequently optimized through a central composite design. The method operable design region was approved by the establishment of a robust zone using Monte Carlo simulation and capability analysis. The validation of the HPLC method was performed based on the total error concept. The relative bias was varied between ─ 11.6 % and 10.5 % and the RSD values for repeatability and intermediate precision were below 4.4 % in all cases. The limits of detection (LOD) ranged between 0.17 - 0.90 µg/mL and were adequate for the specific application. The developed method was successfully applied to the analysis of the studied drugs in in-vitro drug release samples obtained from 3D-printed tablets combining the above-mentioned active pharmaceutical ingredients (APIs).

Local drug delivery challenges and innovations in spinal neurosurgery.

The development of novel therapeutics in the field of spinal neurosurgery faces a litany of translational challenges. Achieving precise drug targeting within the confined spaces associated with the spinal cord, canal and vertebra requires the development of next generation delivery systems and devices. These must be capable of overcoming inherent barriers related to drug diffusion, whilst concurrently ensuring optimal drug distribution and retention. In this review, we provide an overview of the most recent advances in the therapeutic management of diseases and disorders affecting the spine, including systems and devices capable of releasing small molecules and biopharmaceuticals that help eliminate pain and restore the mechanical function and stability of the spine. We highlight material-based approaches and minimally invasive techniques that can be employed to provide control over drug release kinetics and improve retention. We also seek to explore how the newest advancements in nanotechnology, biomaterials, additive manufacturing technologies and imaging modalities can be employed in this translational pursuit. Finally, we discuss the landscape of clinical trials and recently approved products aimed at overcoming the complexities associated with drug delivery to the spine.

In situ triggered, floating delivery systems of capsaicin for prolonged gastroprotection.

Capsaicin (CAP) has been implicated as a gastroprotective agent in the treatment of peptic ulcers. However, its oral administration is hampered by its poor aqueous solubility and caustic effect at high administered doses. To address these limitations, we describe the development of gastric floating, sustained release electrospun films loaded with CAP. The nanofiber films were formulated using the polymers Eudragit RL/RS and sodium bicarbonate (SB) as the effervescent agent. The films were tested for their physicochemical properties, and film buoyancy and in vitro release of CAP were assessed in simulated gastric fluid. The cytocompatibility and anti-inflammatory properties of the films were evaluated in lipopolysaccharide (LPS)-stimulated Caco-2 cells. The amorphous films showed improved wettability, a short floating lag time (<1 s) and a total floating time of over 24 h accompanied by sustained CAP release for up to 24 h. CAP-loaded films demonstrated biocompatibility with Caco-2 cells and potential cytoprotective effects by attenuating inflammatory cytokine and reactive oxygen species (ROS) production in LPS-stimulated Caco-2 cells. The gastric floating electrospun films could serve as a platform for sustained and stomach-specific drug delivery applications.

A floating 3D printed polypill formulation for the coadministration and sustained release of antihypertensive drugs.

Polypharmacy is a common issue, especially among elderly patients resulting in administration errors and patient inconvenience. Hypertension is a prevalent health condition that frequently leads to polypharmacy, as its treatment typically requires the co-administration of more than one different Active Pharmaceutical Ingredients (API's). To address these issues, floating hollow torus-shaped dosage forms were developed, aiming at providing prolonged gastric retention and sustained drug release. The dosage forms (polypills) containing three anti-hypertensive API's (diltiazem (DIL), propranolol (PRP) and hydrochlorothiazide (HCTZ)) were created via Fused Deposition Modelling 3D printing. A multitude of the dosage forms were loaded into a capsule and the resulting formulation achieved prolonged retention times over a 12-hour period in vitro, by leveraging both the buoyancy of the dosage forms, and the "cheerios effect" that facilitates the aggregation and retention of the dosage forms via a combination of surface tension and shape of the objects. Physicochemical characterization methods and imaging techniques were employed to investigate the properties and the internal and external structure of the dosage forms. Furthermore, an ex vivo porcine stomach model revealed substantial aggregation, adhesion and retention of the 3D printed dosage forms in porcine stomach. In vitro dissolution testing demonstrated almost complete first-order release of PRP and DIL (93.52 % and 99.9 %, respectively) and partial release of HCTZ (65.22 %) in the 12 h timeframe. Finally, a convolution-based single-stage approach was employed in order to predict the pharmacokinetic (PK) parameters of the API's of the formulation and the resemblance of their PK behavior with previously reported data.

Small patients, big challenges: navigating pediatric drug manipulations to prevent medication errors - a comprehensive review.

INTRODUCTION: Medication errors during drug manipulations in pediatric care pose significant challenges to patient safety and optimal medication management. Epidemiological studies have revealed a high prevalenceof medication errors throughout the medication process. Due to the lack of age-appropriate dosage forms, medication manipulation is common in pediatric drug administration. The consequences of these manipulations on drug efficacy and safety could be devastating, highlighting the need for evidence-based guidelines and standardized compounding practices. AREAS COVERED: This review focuses on examining medication errors in pediatric care and delving into the manipulation of medicinal products. EXPERT OPINION: The observed prevalence of medication errors and manipulations underscores the importance of addressing these issues to enhance patient safety and improve medication outcomes in pediatric care. Overall, the development of age-appropriate formulations and the dissemination of comprehensive clinical guidelines are essential steps toward improving medication safety and minimizing manipulations in pediatric healthcare settings.

Modular Titratable Polypills for Personalized Medicine and Simplification of Complex Medication Regimens.

Simplification of complex medication regimens in polypharmacy positively contributes to treatment adherence and cost-effective improved health outcomes. Even though fixed dose combination (FDC) drug products are the only currently available single dose poly-pill regimens, the lack of flexibility in dose adjustment of a single drug in the combination limits their efficacy. To fill the existing gap in drug dose personalization and simplification of complex medication regimens commonly encountered in the treatment of cardiovascular disease, tuberculosis, and tapering of corticosteroid therapy, a modular titratable polypill approach that simultaneously addresses both aspects is proposed. The polypill consists of modular units that contain different drugs at incremental or decremental doses to be assembled in a single titratable polypill at the required dose for each drug through a stacking or interlocking process. The variable dose (VD) modular tablets are subjected to quality control tests and found to comply to pharmacopeia's acceptance criteria and requirements specified in the respective drug monographs. A cost-effectiveness analysis is conducted supporting the VD strategy as cost-effective compared to the FDC strategy and more effective and less expensive than standard of care. The VD approach stands to enable pill burden reduction, ease of administration, enhancement of treatment adherence, and potential cost-saving benefits.

Pediatric and Geriatric-Friendly Buccal Foams: Enhancing Omeprazole Delivery for Patients Encountering Swallowing Difficulties.

Buccal foams containing omeprazole (OME) have been developed as potential drug delivery systems for individuals encountering swallowing difficulties, particularly pediatric and geriatric patients. The buccal foams were formulated from lyophilized aqueous gels of maltodextrin, used as a sweetener, combined with various polymers (alginate, chitosan, gelatin, tragacanth) to fine tune their structural, mechanical, and physicochemical properties. Consistent with the requirements for efficient drug delivery across buccal epithelium, the foam comprised of hydroxypropyl methylcellulose and alginate (HPMC-Alg-OME), exhibited moderate hardness and high mucoadhesion resulting to prolonged residence and increased transport of the active across porcine epithelium. The HPMC-Alg-OME foam induced a 30-fold increase in the drug's apparent permeability across porcine buccal tissue, compared to the drug suspension. The developed buccal foams exhibited excellent stability, as evidenced by the unchanged omeprazole content even after six months of storage under ambient conditions (20 °C and 45% RH). Results indicate that buccal foams of omeprazole may address the stability and ease of administration issues related to oral administration of the drug, particularly for children and elderly patients who have difficulty swallowing solid dosage forms.

Exploring the Role of Self-Nanoemulsifying Systems in Drug Delivery: Challenges, Issues, Applications and Recent Advances.

Nanotechnology has attracted researchers around the globe owing to the small size and targeting properties of the drug delivery vectors. The interest in self-nanoemulsifying drug delivery systems (SNEDDS) has shown an exponential increase from the formulator's point of view. SNEDDS have shown wide applicability in terms of controlled and targeted delivery of various types of drugs. They chemically consist of oil, surfactants and co-surfactants that decrease the emulsion particle size to the range of <100 nm. However, stability issues such as drug precipitation during storage, incompatibility of ingredients in shell, decrease their application for the long run and these issues have been highlighted in this paper. The current review throws limelight on the biological aspects and process parameters. In addition, the process of absorption from GI is also discussed in detail. SNEDDS have been utilized as a treatment option for various diseases like cancer, diabetes, and ocular and pulmonary diseases. Along with this, the authors highlight the advances involving in vivo and in vitro lipolysis studies on SNEDDS, also highlighting recent innovations in this field, such as novel combinations of drug-free solid SNEDDS + solid dispersions, lipid-modified chitosan containing mucoadhesive SNEDDS, pHsensitive SNEDDS and several others.