Lecithin Organogel: A Promising Carrier for the Treatment of Skin Diseases.

Skin is the largest organ of the human body, as it protects the body from the external environment. Nowadays, skin diseases and skin problems are more common, and millions of people are affected daily. Skin diseases are due to numerous infectious pathogens or inflammatory conditions. The increasing demand for theoretical research and practical applications has led to the rising prominence of gel as a semisolid material. To this end, organogels has been widely explored due to their unique composition, which includes organic solvents and mineral or vegetable oils, among others. Organogels can be described as semisolid systems wherein an organic liquid phase is confined within a three-dimensional framework consisting of self-assembled, cross-linked, or entangled gelator fibers. These gels have the ability to undergo significant expansion and retain substantial amounts of the liquid phase, reaching up to 99% swelling capacity. Furthermore, they respond to a range of physical and chemical stimuli, including temperature, light, pH, and mechanical deformation. Notably, due to their distinctive properties, they have aroused significant interest in a variety of practical applications. Organogels favor the significant encapsulation and enhanced permeation of hydrophobic molecules when compared with hydrogels. Accordingly, organogels are characterized into lecithin organogels, pluronic lecithin organogels, sorbitan monostearate-based organogels, and eudragit organogels, among others, based on the nature of their network and the solvent system. Lecithin organogels contain lecithin (natural and safe as a living cell component) as an organogelator. It acts as a good penetration enhancer. In this review, first we have summarized the fundamental concepts related to the elemental structure of organogels, including their various forms, distinctive features, methods of manufacture, and diverse applications. Nonetheless, this review also sheds light on the delivery of therapeutic molecules entrapped in the lecithin organogel system into deep tissue for the management of skin diseases and provides a synopsis of their clinical applications.

Engineered Nano-carrier systems for the oral targeted delivery of follicle stimulating Hormone: Development, characterization, and, assessment of in vitro and in vivo performance and targetability.

Follicle stimulating hormone (FSH) is widely used for the treatment of female infertility, where the level of FSH is suboptimal due to which arrest in follicular development and anovulation takes place. Currently, only parenteral formulations are available for FSH in the market. Due to the drawbacks of parenteral administration and the high market shares of FSH, there is a need for easily accessible oral formulation. Therefore, enteric coated capsules filled with FSH loaded nanostructured lipid carriers (NLCs) or liposomes were prepared. Preliminary studies such as circular dichroism, SDS-PAGE, FTIR and ELISA were conducted to analyze FSH. Prepared formulations were optimized with respect to the size, polydispersity index, zeta potential, and entrapment efficiency using the design of experiments. Optimized formulations were subjected to particle counts and distribution analysis, TEM analysis, in vitro drug release, dissolution of enteric coated capsules, cell line studies, everted sac rat's intestinal uptake study, pharmacokinetics, pharmacodynamics, and stability studies. In the case of liposomes, RGD conjugation was done by carbodiimide chemistry and conjugation was confirmed by FTIR, 1HNMR and Raman spectroscopy. The prepared formulations were discrete and spherical. The release of FSH from enteric coated capsules was slow and sustained. The increased permeability of nano-formulations was observed in Caco-2 monoculture as well as in Caco-2 and Raji-B co-culture models. NLCs and liposomes showed an improvement in oral bioavailability and efficacy of FSH in rats. This may be due to mainly chylomicron-assisted lymphatic uptake of NLCs; whereas, in the case of liposomes, RGD-based targeting of ß1 integrins of M cells on Peyer's patches may be the main reason for the better effect by FSH. FSH was found to be stable chemically and conformationally. Overall, the study reveals the successful development and evaluation of FSH loaded NLCs and liposomes.

Effective Cancer Management: Inimitable Role of Phytochemical Based Nano- Formulations.

BACKGROUND: Global cancer statistics defines the severity of disease even after significant research worldwide. PROBLEM: Failure of the currently available treatment approaches, including surgery, radiation therapy and traditional chemotherapy. AIM: The aim of this review is to discuss the role of phytochemical based nano-formulations for treatment of cancer. DISCUSSION: In the past few decades, phytochemicals have gained popularity for acting as a potential anticancer treatment with low systemic toxicity, especially in terms of cell cycle control and cancer cell killing. Natural resources, with their immense structural variety, serve as a vital source of fresh, therapeutically useful new chemical entities for the treatment of cancer. Vinca alkaloids (VCR), vinblastine, vindesine, vinorelbine, taxanes (PTX), podophyllotoxin and its derivatives (etoposide (ETP), teniposide, camptothecin (CPT) and its derivatives (topotecan, irinotecan), anthracyclines (doxorubicin, daunorubicin, epirubicin, idarubicin, as natural products or their derivatives account for half of all anticancer drugs approved worldwide, and they have been developed utilising the knowledge learned from the natural small molecules or macromolecules. Trabectedin, an epothilone derivative, ixabepilone, and temsirolimus, three new anticancer medications launched in 2007, were derived from microbial origins. Current therapy regimens require selective drug targeting to enhance efficacy against cancer cells while normal cells remain unharmed. Modified medications and systems for drug delivery based on nanotechnology are in the process of being explored and launched in the industry for enhanced therapy and management of cancer, along with promising outcomes. Many obstacles related to cancer cell drug delivery can be overcome by using nano-particulate drug carriers, including enhancing the stability and solubility of the drug, prolonging half-lives of the drug in the blood, decreasing side effects to undesired organs, and increasing medication concentration at the desired site. The scientific initiatives and studies concerning the use of nanotechnology for some selective compounds derived from plants are discussed in this review article. CONCLUSION: The present review highlights the phytochemical-based nanoformulations and their strategies in the development of novel systems of drug delivery such as nano-liposomes, functionalized nanoparticles (NPs), and polymer nano-conjugates, SNEDDS (Self nano emulsifying drug delivery system) as this review paper depicts, as well as their rewards over conventional systems of drug delivery, as evidenced by improved biological activity depicted in their in vitro and in vivo anticancer assays.

Experimental studies on droplet characteristics in a microfluidic flow focusing droplet generator: effect of continuous phase on droplet encapsulation.

The efficacy of droplet-based microfluidic assays depends on droplet size, pattern, generation rate, etc. The size of the droplet is affected by numerous variables as flow rate ratio, viscosity ratio, microchannel geometry, surfactants, nature of fluids and other dimensionless numbers. This work reports rigorous analysis and optimization of the behavior of droplets with change in flow rate ratio and viscosity ratio in a flow-focusing device. Droplets were produced for different flow rate ratios maintaining a constant aqueous phase and varying the continuous phase, to have capillary numbers ranging from 0.01 to 0.1. It was observed that the droplet size decreased with the increase in flow rate ratio, and vice versa. It was noted that as the viscosity ratio was increased, the dispersed phase elongated before the complete breakup and long droplets were formed in the microchannel. Smaller droplets were formed for lower viscosity ratios with a combination of higher flow rate ratios. An empirical relation has been developed to predict the droplet length in terms of capillary number and flow rate ratio for different viscosity ratios. In addition, microparticle encapsulation in individual droplets was attempted to realize the effect of flow rate of the continuous phase for various flow rate ratios on encapsulation efficiency.

Droplet-based lab-on-chip platform integrated with laser ablated graphene heaters to synthesize gold nanoparticles for electrochemical sensing and fuel cell applications.

Controlled, stable and uniform temperature environment with quick response are crucial needs for many lab-on-chip (LOC) applications requiring thermal management. Laser Induced Graphene (LIG) heater is one such mechanism capable of maintaining a wide range of steady state temperature. LIG heaters are thin, flexible, and inexpensive and can be fabricated easily in different geometric configurations. In this perspective, herein, the electro-thermal performance of the LIG heater has been examined for different laser power values and scanning speeds. The experimented laser ablated patterns exhibited varying electrical conductivity corresponding to different combinations of power and speed of the laser. The conductivity of the pattern can be tailored by tuning the parameters which exhibit, a wide range of temperatures making them suitable for diverse lab-on-chip applications. A maximum temperature of 589 °C was observed for a combination of 15% laser power and 5.5% scanning speed. A LOC platform was realized by integrating the developed LIG heaters with a droplet-based microfluidic device. The performance of this LOC platform was analyzed for effective use of LIG heaters to synthesize Gold nanoparticles (GNP). Finally, the functionality of the synthesized GNPs was validated by utilizing them as catalyst in enzymatic glucose biofuel cell and in electrochemical applications.

Organophosphorus pesticide quinalphos (Ekalux 25 E.C.) reduces sperm functional competence and decreases the fertilisation potential in Swiss albino mice.

Quinalphos (QP) is one of the most commonly used organophosphate pesticide for agriculture. In this study, adult Swiss albino male mice were orally administered with 0.25, 0.5 and 1.0 mg/kg of QP (Ekalux 25 E.C.) for ten consecutive days and the reproductive function was assessed at 35 and 70 days after QP treatment. At highest dose (1.0 mg/kg), QP exposure resulted in significant decrease in motility and increase in sperm head defects and DNA damage. Pharmacokinetic data showed a threefold increase in concentration of QP in the testis as compared to serum. QP was detectable in testes even after 24 hr of administration indicating slow clearance from tissue. In addition, high oestradiol, low testosterone level with a parallel increase in aromatase and cytochrome P450 transcript levels was observed. Significant decrease in fertilisation, lower blastocyst rate and poor blastocyst quality was observed when spermatozoa collected from QP exposed mice were subjected to in vitro fertilisation. In conclusion, exposure of QP to male mice decreases the sperm functional competence and fertilising ability, which appears to be mediated through elevated oxidative stress and altered steroidogenesis in testes.

Hot liquid extrusion assisted drug-cyclodextrin complexation: a novel continuous manufacturing method for solubility and bioavailability enhancement of drugs.

In this study, drug-cyclodextrin (CD) complexes were prepared using hot liquid extrusion (HLE) process with an aim to improve solubility and bioavailability of carbamazepine. Saturation solubility studies of CBZ in water and different pH media showed a pH-independent solubility. Phase solubility studies of CBZ at different molar concentrations of beta-cyclodextrin (ß-CD) and hydroxypropyl beta-cyclodextrin (HP-ß-CD) indicated AL-type solubility profile with stability constants of 574 M-1 and 899 M-1 for ß-CD and HP-ß-CD. Drug-ß-CD and drug-HP-ß-CD complexes were prepared using HLE process and conventional methods (such as physical mixture, kneading method, and solvent evaporation) as well. Optimized complexes prepared using HLE viz. CBP-4 and CHP-2 showed a solubility of 4.27 ± 0.09 mg/mL and 6.39 ± 0.09 mg/mL as compared to plain CBZ (0.140 ± 0.007 mg/mL). Formation of drug-CD inclusion complexes was confirmed using DSC, FTIR, and XRD studies. Drug release studies indicated highest release of CBZ from CHP-2 (98.69 ± 2.96%) compared to CBP-4 (82.64 ± 2.45%) and plain drug (13.47 ± 0.54%). Complexes prepared using kneading showed significantly lesser drug release (KMB 75.52 ± 2.68% and KMH 85.59 ± 2.80%) as that of CHP-2 and CBP-4. Pre-clinical pharmacokinetic studies in Wistar rats indicated a significant increase in Cmax, Tmax, AUC, and mean residence time for CHP-2 compared to KMH and plain CBZ. All these results suggest that HLE is an effective method to increase the solubility of poorly water-soluble drugs. Graphical Abstract.

HFR Projector Camera Based Visible Light Communication System for Real-Time Video Streaming.

This study develops a projector-camera-based visible light communication (VLC) system for real-time broadband video streaming, in which a high frame rate (HFR) projector can encode and project a color input video sequence into binary image patterns modulated at thousands of frames per second and an HFR vision system can capture and decode these binary patterns into the input color video sequence with real-time video processing. For maximum utilization of the high-throughput transmission ability of the HFR projector, we introduce a projector-camera VLC protocol, wherein a multi-level color video sequence is binary-modulated with a gray code for encoding and decoding instead of pure-code-based binary modulation. Gray code encoding is introduced to address the ambiguity with mismatched pixel alignments along the gradients between the projector and vision system. Our proposed VLC system consists of an HFR projector, which can project 590 × 1060 binary images at 1041 fps via HDMI streaming and a monochrome HFR camera system, which can capture and process 12-bit 512 × 512 images in real time at 3125 fps; it can simultaneously decode and reconstruct 24-bit RGB video sequences at 31 fps, including an error correction process. The effectiveness of the proposed VLC system was verified via several experiments by streaming offline and live video sequences.

Novel pH-sensitive interpenetrated network polyspheres of polyacrylamide-g-locust bean gum and sodium alginate for intestinal targeting of ketoprofen: In vitro and in vivo evaluation.

In this report, novel pH-sensitive interpenetrated network (IPN) polyspheres were developed utilizing polyacrylamide-g-locust bean gum (PAAm-g-LBG) in combination with sodium alginate (SA) to achieve intestinal targeted delivery of ketoprofen. PAAm-g-LBG was synthesized under microwave irradiation wherein ceric ammonium nitrate was used as reaction initiator and then conversion of PAAm-g-LBG as pH-sensitive copolymer was carried out by alkaline hydrolysis. The PAAm-g-LBG copolymer was characterized through 1H-NMR, FTIR and elemental analysis. The IPN polyspheres exhibited pH-depended swelling or de-swelling with the alteration of surrounding pH. The in-vitro release of drug from IPN polyspheres was found to be higher (≈ 90%) in phosphate buffer of pH 7.4 in comparison with that in pH 1.2 buffer (10.6%). The in-vivo pharmacokinetic, anti-inflammatory screening and stomach histopathology studies performed on Wistar rats revealed pH sensitivity of IPN polyspheres where ketoprofen was successfully targeted to small intestine resulting in reduced side effects of ketoprofen like ulcer formation, erosion of gastric mucosa and hemorrhages.

Asenapine maleate-loaded nanostructured lipid carriers: optimization and in vitro, ex vivo and in vivo evaluations.

AIM: To prepare nanostructured lipid carriers (NLCs) loaded with asenapine maleate (ASPM) to increase its oral bioavailability by intestinal lymphatic uptake. MATERIALS & METHODS: ASPM-NLCs were prepared by ultrasound dispersion technique, by adopting Design of Experiment approach, and characterized. RESULTS: The optimized formulation exhibited good physicochemical parameters. Differential scanning calorimetry and x-ray diffraction studies indicated the amorphized nature of ASPM in lipid matrix. In vitro drug release study indicated the sustained release of drug from NLCs. ASPM-NLCs showed greater permeability across Caco2 cells and everted rat ileum. ASPM-NLCs showed greater cellular uptake, superior preclinical oral bioavailability and higher efficacy in reducing the L-DOPA-carbidopa-induced locomotor count compared with plain drug. CONCLUSION: ASPM-NLCs were successfully developed that showed enhanced performance both in vitro and in vivo.

Cyclodextrins as Carriers in Targeted Delivery of Therapeutic Agents: Focused Review on Traditional and Inimitable Applications.

The objective of the article is to provide a comprehensive review on the application of cyclodextrin complexation in the delivery of drugs, bioactive molecules or macromolecules, with more emphasis on targeted drug delivery. Classically the cyclodextrins have been considered only as a means of improving the solubility of drugs; however, many attempts have been made to use cyclodextrins as drug delivery carriers. The cyclodextrin surface can be modified with various ligands for active targeting of drugs. It can also be passively targeted through various triggering mechanisms like thermal, magnetic, pH dependent, light dependent, ultrasound, etc. A comprehensive literature review has been done in the area of drug delivery using cyclodextrins. Applications of inclusion complexes in the drug delivery through various routes with examples are discussed. This review focuses on receptor mediated active targeting as well as stimuli responsive passive targeting of drugs/genes by using cyclodextrins. The article provides a detailed insight of the use of cyclodextrins and their derivatives on the targeted delivery of the drugs/genes.

Active Targeting of Drugs and Bioactive Molecules via Oral Administration by Ligand-Conjugated Lipidic Nanocarriers: Recent Advances.

The oral route is the most widely accepted and commonly used route for administration. However, this route may not be suitable for certain drug candidates which suffer from the problem of low aqueous solubility and gastrointestinal absorption and extensive first-pass effect. Nanotechnology-based approaches can be taken up as remedies to overcome the disadvantages associated with the oral route. Among the various nanocarriers, lipidic nanocarriers are widely used for oral delivery of bioactive molecules owing to their several advantages. Active targeting of bioactive molecules via lipidic nanocarriers has also been widely attempted to improve oral bioavailability and to avoid first-pass effect. This active targeting approach involves the use of ligands grafted or conjugated onto a nanocarrier that is specific to the receptors. Active targeting increases the therapeutic efficacy as well as reduces the toxic side effects of the drug or bioactive molecules. This review mainly focuses on the challenges involved in the oral delivery of drugs and its approaches to overcome the challenges using nanotechnology, specifically focusing on lipidic nanocarriers like liposomes, solid lipid nanoparticles, and nanostructured lipid carriers and active targeting of drug molecules by making use of ligand-conjugated lipidic nanocarriers.

Targeting the intestinal lymphatic system: a versatile path for enhanced oral bioavailability of drugs.

INTRODUCTION: The major challenge of first pass metabolism in oral drug delivery can be surmounted by directing delivery toward intestinal lymphatic system (ILS). ILS circumvents the liver and transports drug directly into systemic circulation via thoracic duct. Lipid and polymeric nanoparticles are transported into ILS through lacteal and Peyer's patches. Moreover, surface modification of nanoparticles with ligand which is specific for Peyer's patches enhances the uptake of drugs into ILS. Bioavailability enhancement by lymphatic uptake is an advantageous approach adopted by scientists today. Therefore, it is important to understand clear insight of ILS in targeted drug delivery and challenges involved in it. AREAS COVERED: Current review includes an overview of ILS, factors governing lymphatic transport of nanoparticles and absorption mechanism of lipid and polymeric nanoparticles into ILS. Various ligands used to target Peyer's patch and their conjugation strategies to nanoparticles are explained in detail. In vitro and in vivo models used to assess intestinal lymphatic transport of molecules are discussed further. EXPERT OPINION: Although ILS offers a versatile pathway for nanotechnology based targeted drug delivery, extensive investigations on validation of the lymphatic transport models and on the strategies for gastric protection of targeted nanocarriers have to be perceived in for excellent performance of ILS in oral drug delivery.

Skin Delivery of EGCG and Silibinin: Potential of Peptide Dendrimers for Enhanced Skin Permeation and Deposition.

The aim of the present study was to evaluate the ability of the peptide dendrimers to facilitate transdermal delivery of antioxidants, silibinin, and epigallocatechin-3-gallate (EGCG). Drug-peptide dendrimer complexes were prepared and evaluated for their ability to permeate across the skin. The data revealed the ready formation of complexes between drug and peptide dendrimer in a molar ratio of 1:1. In vitro permeation studies using excised rat skin and drug-peptide dendrimer complexes showed highest values for cumulative drug permeation at the end of 12 h (Q12), with corresponding permeability coefficient (Kp) and enhancement ratio values also determined at this time point. With silibinin, 3.96-, 1.81-, and 1.06-fold increase in skin permeation was observed from silibinin-peptide dendrimer complex, simultaneous application of silibinin + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. With EGCG, 9.82-, 2.04-, and 1.72-fold increase in skin permeation was observed from EGCG-peptide dendrimer complex, simultaneous application of EGCG + peptide dendrimer, and pretreatment of skin with peptide dendrimer, respectively, in comparison with passive diffusion. The present study demonstrates the application of peptide dendrimers in effectively delivering antioxidants such as EGCG and silibinin into the skin, thus offering the potential to provide antioxidant effects when delivered via appropriately formulated topical preparations.

Anti-Inflammatory and Antinociceptive Activities of a Hydroethanolic Extract of Tamarindus indica Leaves.

The present study aimed to investigate the anti-inflammatory and anti-nociceptive potential of a hydroethanolic extract of Tamarindus indica L. leaves (HTI) along with its possible mode of action. The anti-inflammatory activity of HTI was estimated by carrageenan-induced hind paw oedema in male Wistar albino rats. Furthermore, HTI was assessed to determine its effects on membrane stabilization. The antinociceptive action was determined by acetic acid-induced writhing, tail-flick, and the hot plate model. Oral administration of HTI at the dose of 500, 750, and 1000 mg/kg body weight produced significant (P< 0.01) anti-inflammatory as well as antinociceptive actions in a dose-dependent manner. Among all tested doses, 1000 mg/kg, p. o. reduced carrageenan-induced rat paw oedema at 1, 2, 3, and 4 h. Moreover, the 1000 mg/kg dose exhibited maximum percentage inhibition of acetic acid-induced writhing (48.9%), whereas standard drug diclofenac (25 mg/kg, p. o.) showed maximum inhibition (50.9%) of writhing. In the hot plate model, HTI (1000 mg/kg, orally) increased mean basal reaction time after 120 min (7.12±0.05 sec). In the tail flick model, HTI increased the maximum percentage of latency (36.06%), whereas the standard drug pethidine (4 mg/kg, intraperitoneally) showed maximum percentage of latency (43.85%) after 60 min. The findings of the present study supported anti-inflammatory and antinociceptive claims of T. indica as were mentioned in Indian traditional and folklore practices.