Collagen loaded nano-sized surfactant based dispersion for topical application: formulation development, characterization and safety study.

Collagen, a high molecular weight, hydrophilic and highly abundant protein is known to have anti-ageing, anti-wrinkle, anti-acne, anti-scar and wound healing properties. High molecular weight and hydrophilic nature hinder its effective topical delivery. So, the objective of present study was to develop effective topical nano-surfactant dispersion (NSD) for collagen delivery. NSD was prepared from sorbitan monostearate (Span60) and cholesterol using ethanol injection method followed by probe sonication. NSD was characterized for entrapment efficiency (%EE), size and size distribution (Z-avg and polydispersity index (PDI)), shape, zeta-potential (ζ), in vitro drug release, skin hydration and skin irritation test and histopathological examination. Optimized NSD (NSD3) had %EE, z-avg, PDI and ζ-potential of 77.56% ± 1.09%, 158.1 ± 2.31 nm, 0.211 and -17.2 ± 0.64 mV, respectively. In in vivo skin hydration test, NSD treatment showed nearly 2.5-fold and 3-fold increase in the thickness of stratum corneum (SC) as compared to the collagen gel treated and untreated skin, respectively. The mean scores of skin irritation test in two animal species, rats and rabbits, were found to be 1.42 ± 1.01 and 1.71 ± 0.29, respectively, indicating the non-irritant nature of collagen loaded NSD. Histopathology of the skin after application of developed NSD showed non-significant changes in skin anatomy indicating its safe nature.

Nanocrystals as an emerging nanocarrier for the management of dermatological diseases.

Skin conditions are amongst the most prevalent health issues in the world and come with a heavy economic, social, and psychological burden. Incurable and chronic skin conditions like eczema, psoriasis, fungal infections are linked to major morbidity in the manner of physical pain and a reduction in quality life of patients. Several drugs have difficulties for penetrating the skin due to the barrier mechanism of the skin layers and the incompatible physicochemical characteristics of the drugs. This has led to the introduction of innovative drug delivery methods. Currently, formulations depend on nanocrystals have indeed been researched for topical administration of drugs and have resulted in enhanced skin penetration. This review focuses on skin penetration barriers, modern methods to enhance topical distribution, and the use of nanocrystals to overcome these barriers. By means of mechanisms such as adherence to skin, creation of diffusional corona, targeting of hair follicles, and the generation of a greater concentration gradient throughout the skin, nanocrystals could enhance transport across the skin. Scientists working on product formulations incorporating chemicals that are "challenging-to-deliver" topically may find the most current findings to be of relevance.

Development and evaluation of nanosized niosomal dispersion for oral delivery of Ganciclovir.

Encapsulation of Ganciclovir in lipophilic vesicular structure may be expected to enhance the oral absorption and prolong the existence of the drug in the systemic circulation. So the purpose of the present study was to improve the oral bioavailability of Ganciclovir by preparing nanosized niosomal dispersion. Niosomes were prepared from Span40, Span60, and Cholesterol in the molar ratio of 1:1, 2:1, 3:1, and 3:2 using reverse evaporation method. The developed niosomal dispersions were characterized for entrapment efficiency, size, shape, in vitro drug release, release kinetic study, and in vivo performance. Optimized formulation (NG8; Span60:Cholesterol 3:2 molar ratio) has shown a significantly high encapsulation of Ganciclovir (89±2.13%) with vesicle size of 144±3.47 nm (polydispersity index [PDI]=0.08). The in vitro release study signifies sustained release profile of niosomal dispersions. Release profile of prepared formulations have shown that more than 85.2±0.015% drug was released in 24 h with zero-order release kinetics. The results obtained also revealed that the types of surfactant and Cholesterol content ratio altered the entrapment efficiency, size, and drug release rate from niosomes. In vivo study on rats reveals five-time increment in bioavailability of Ganciclovir after oral administration of optimized formulation (NG8) as compared with tablet. The effective drug concentration (>0.69 µg/mL in plasma) was also maintained for at least 8 h on administration of the niosomal formulation. In conclusion, niosomes can be proposed as a potential oral delivery system for the effective delivery of Ganciclovir.

Dual approach utilizing self microemulsifying technique and novel P-gp inhibitor for effective delivery of taxanes.

In the present work, concomitant use of self-microemulsifying drug delivery systems (SMEDDS) and a novel third-generation P-gp inhibitor, GF120918 (elacridar), for the effective transport of taxanes (paclitaxel and docetaxel) across an in vitro model of the intestinal epithelium and uptake into tumor cells were investigated. On the basis of solubility studies and ternary phase diagrams, different SMEDDS formulations of taxanes were prepared and characterized. In caco-2 cell permeation study, paclitaxel-loaded SMEDDS along with GF120918 showed a four-fold increase in apparent permeability, while docetaxel-loaded SMEDDS in combination with GF120918 showed a nine-fold increase in permeability, as compared to plain drug solution. Cell uptake studies on A549 cells were performed with microemulsions formed from both SMEDDS formulations loaded with rhodamine 123 dye and showed good uptake than plain dye solution. Confocal laser scanning microscopic images further confirmed the higher uptake of both SMEDDS formulations in the presence of GF120918.

Stability-indicating ultra-performance liquid chromatography method for the estimation of thymoquinone and its application in biopharmaceutical studies.

Thymoquinone (THQ) is known for its neuroprotective and anti-convulsant properties in preclinical studies. We herewith describe a simple, rapid, selective, sensitive and stability-indicating UPLC method for the estimation of THQ and its application to biopharmaceutical studies such as in vitro release from nanoparticulate system and in vivo pharmacokinetic study. The method employed gradient elution using a Waters Acquity HSS-T3 C(18) (100 × 2.1 mm, 1.8 µm) UPLC column. The mobile phase consisted of water and acetonitrile, pumped at a flow rate of 0.5 mL/min. The injection volume was 5 µL and THQ was monitored at 294 nm wavelength with a total run time of 6 min. In solution as well as in plasma, the method was found to be linear (r ≥ 0.998), precise (CV ≤ 2.45%) and accurate (recovery ≥ 84.8%) in the selected concentration range of 0.1-0.8 µg/mL. Forced degradation studies revealed that THQ undergoes degradation under acidic, basic, oxidation and UV light stress conditions. However, the developed UPLC method could effectively resolve degradation product peaks from THQ. Further, no interference was found at the retention time of THQ from any plasma components, indicating selectivity of the developed method. For solutions, the limits of detection and quantitation of the method were found to be 0.001 and 0.0033 µg/mL, respectively; while in plasma they were 0.006 and 0.02 µg/mL, respectively. The validated method was successfully applied to quantify THQ in dissolution medium as well as oral in vivo pharmacokinetic study of THQ suspension and THQ- solid lipid nanoparticle (THQ-SLN) formulation. A 2-fold increase in the relative bioavailability was observed with the THQ-SLN compared with THQ. The results indicate that the SLN significantly increased plasma concentrations and retention within the systemic circulation.

A validated HPTLC method for determination of terbutaline sulfate in biological samples: Application to pharmacokinetic study.

Terbutaline sulfate (TBS) was assayed in biological samples by validated HPTLC method. Densitometric analysis of TBS was carried out at 366 nm on precoated TLC aluminum plates with silica gel 60F254 as a stationary phase and chloroform-methanol (9.0:1.0, v/v) as a mobile phase. TBS was well resolved at RF 0.34 ± 0.02. In all matrices, the calibration curve appeared linear (r (2) â©¾ 0.9943) in the tested range of 100-1000 ng spot(-1) with a limit of quantification of 18.35 ng spot(-1). Drug recovery from biological fluids averaged ⩾95.92%. In both matrices, rapid degradation of drug favored and the T 0.5 of drug ranged from 9.92 to 12.41 h at 4 °C and from 6.31 to 9.13 h at 20 °C. Frozen at -20 °C, this drug was stable for at least 2 months (without losses >10%). The maximum plasma concentration (Cpmax) was found to be 5875.03 ± 114 ng mL(-1), which is significantly higher than the maximum saliva concentration (Csmax, 1501.69 ± 96 ng mL(-1)). Therefore, the validated method could be used to carry out pharmacokinetic studies of the TBS from novel drug delivery systems.

Role of phytoconstituents in the management of COVID-19.

BACKGROUND: COVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas. SCOPE AND APPROACH: This review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry through host cell receptors. The use of medicinal plants containing specific phytomoieties could be seen in providing a safer and long-term solution for the population with lesser side effects. Key Findings and Conclusions: Considering the high cost and time-consuming drug discovery process, therapeutic repositioning of existing drugs was explored as treatment option in COVID-19, however several molecules have been retracted as therapeutics either due to no positive outcomes or the severe side effects. These effects call for exploring the alternate treatment options which are therapeutically effective as well as safe. Keeping this in mind, phytopharmaceuticals derived from medicinal plants could be explored as important resources in the development of COVID-19 treatment, as their role in the past for treatment of viral diseases like HIV, MERS-CoV, and influenza has been well reported. Considering this fact, different phytoconstituents such as flavonoids, alkaloids, tannins and glycosides etc. Possessing antiviral properties against coronaviruses and possessing potential against SARS-CoV-2 have been reviewed in the present work.

Sparfloxacin-loaded PLGA nanoparticles for sustained ocular drug delivery.

Poor ocular bioavailability of drugs (<1%) from conventional eye drops (ie, solution, suspension, and ointments) is mainly due to the physiologic barriers of the eye. In general, ocular efficacy is closely related to ocular drug bioavailability, which may be enhanced by increasing corneal drug penetration and prolonging precorneal drug residence time. In our current work, we develop and evaluate a new colloidal system, that is, poly(dl-lactide-co-glycolide) (PLGA) nanoparticles for sparfloxacin ophthalmic delivery, to improve precorneal residence time and ocular penetration. Nanoparticles were prepared by nanoprecipitation technique and characterized for various properties such as particle size, zeta potential, in vitro drug release, statistical model fitting, stability, and so forth. Microbiological assay was carried out against Pseudomonas aeruginosa using the cup-plate method. Precorneal residence time was studied in albino rabbits by gamma scintigraphy after radiolabeling of sparfloxacin by Tc-99m. Ocular tolerance of the developed nanosuspension was also studied by the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method. The developed nanosuspension showed a mean particle size in the range of 180 to 190 nm, suitable for ophthalmic application with zeta potential of -22 mV. In vitro release from the developed nanosuspension showed an extended release profile of sparfloxacin according to the Peppas model. Acquired gamma camera images showed good retention over the entire precorneal area for the developed nanosuspension compared with that of a marketed formulation. The marketed drug formulation cleared very rapidly from the corneal region and reached the systemic circulation through the nasolacrimal drainage system, as significant radioactivity was recorded in kidney and bladder after 6 hours of ocular administration, whereas the developed nanosuspension cleared at a very slow rate (P < .05) and remained at the corneal surface for longer duration, as no radioactivity was observed in the systemic circulation. HET-CAM assay with 0 score in 8 hours indicates the nonirritant property of the developed nanosuspension. The developed lyophilized nanosuspension was found to be stable for a longer duration of time than the conventional marketed formulation with a good shelf life. FROM THE CLINICAL EDITOR: Poor ocular bioavailability of drugs (<1%) from conventional eye drops is mainly due to the eye physiological barriers. In this study, a new colloidal system, PLGA nanoparticle for sparfloxacin ophthalmic delivery was demonstrated to improve precorneal residence time and ocular penetration. The developed lyophilized nanosuspension was found to be stable for longer duration of time than conventional marketed formulations.

Quantitative analysis of safranal in saffron extract and nanoparticle formulation by a validated high-performance thin-layer chromatographic method.

INTRODUCTION: Safranal is an effective anticonvulsant shown to act as an agonist at GABA(A) receptors. Nose to brain delivery via nanoparticle formulation might improve its brain delivery. A selective and sensitive analytical method is required for evaluation of safranal-based novel drug delivery systems. OBJECTIVE: To develop and validate a high-performance thin-layer chromatographic (HPTLC) method for the quantitative analysis of safranal as bulk, in saffron extract and in developed safranal-loaded nanoparticle formulation. METHODOLOGY: Chromatographic separation was achieved on silica gel pre-coated TLC aluminium plates 60F-254, using n-hexane:ethyl acetate (9 : 1, v/v) as the mobile phase. Quantitative analysis was carried out by densitometry at a wavelength of 310 nm. The method was validated and applied to detect related impurities, to analyse safranal in saffron extract and to evaluate safranal-loaded nanoparticles. RESULTS: Compact spots of safranal were observed at R(f) value 0.51 +/- 0.02. The method was linear (r = 0.9991) between 0.5 and 5.0 ng/spot. The intra- and inter-day precisions were 1.08-2.17 and 1. 86-3.47%, respectively. The limit of detection was 50 ng/spot and the limit of quantification was 150 ng/spot. The method proved to be accurate (recovery 97.4-102.0%) and was selective for safranal. Evaluation of safranal-loaded nanoparticle formulation demonstrated drug loading of 23.0%, encapsulation efficiency of 42.0% and sustained drug release following biphasic pattern. CONCLUSION: The present method is useful for the quantitative and qualitative analysis of safranal and safranal-loaded nanoparticle formulation. It provides significant advantages in terms of greater specificity and rapid analysis.

Emerging significance of flavonoids as P-glycoprotein inhibitors in cancer chemotherapy.

Chemotherapy forms the mainstay of cancer treatment particularly for patients who do not respond to local excision or radiation treatment. However, cancer treatment by drugs is seriously limited by P-glycoprotein (P-gp) associated multi-drug resistance (MDR) in various tumor cells. On the other hand, it is now widely recognized that P-gp also influences drug transport across various biological membranes. P-gp transporter is widely present in the luminal surface of enterocytes, biliary canalicular surface of hepatocytes, apical surface of proximal tubular cells of kidney, endothelial cells of blood brain barrier, etc. thus affecting absorption, distribution, metabolism and excretion of xenobiotics. Clinical significance of above mentioned carrier is appreciated from the fact that more than fifty percent of existing anti-cancer drugs undergo inhibitable and saturable P-gp mediated efflux. Consequently, there is an increasing trend to optimize pharmacokinetics, enhance antitumour activity and reduce systemic toxicity of existing anti-cancer drugs by inhibiting P-gp mediated transport. Although a wide variety of P-gp inhibitors have been discovered, research efforts are underway to identify the most appropriate one. Flavonoids (polyphenolic herbal constituents) form the third generation, non-pharmaceutical category of P-gp inhibitors. The effects produced by some of these components are found to be comparable to those of well-known P-gp inhibitors verapamil and cyclosporine. Identification of effective P-gp modulator among herbal compounds have an added advantage of being safe, thereby making them ideal candidates for bioavailability enhancement, tissue-penetration (e.g. blood brain barrier (BBB)), decreasing biliary excretion and multi-drug resistance modulating agents. The dual effects, i.e. P-gp modulation and antitumor activity, of these herbal derivatives may synergistically act in cancer chemotherapy. This paper presents an overview of the investigations on the feasibility and application of flavonoids as P-gp modulators for improved efficacy of anti-cancer drugs like taxanes, anthracyclines, epipodophyllotoxins, camptothecins and vinca alkaloids. The review also focuses on flavonoid-drug interactions as well as the reversal activity of flavonoids useful against MDR. In addition, the experimental models which could be used for investigation on P-gp mediated efflux are also discussed.

Development and clinical trial of nano-atropine sulfate dry powder inhaler as a novel organophosphorous poisoning antidote.

The aim of the work was to develop, characterize, and carry out a clinical trial with nano-atropine sulfate (nano-AS) dry powder inhaler (DPI), because this route may offer several advantages over the conventional intramuscular route as an emergency treatment, including ease of administration and more rapid bioavailability. Different batches of nanoparticles of AS were produced using variants of nanoprecipitation method. The influence of the process parameters, such as the types and quantity of solvent and nonsolvent, the stirring speed, the solvent-to-nonsolvent volume ratio, and the drug concentration, was investigated. The methodology resulted in optimally sized particles. Bulk properties of the particles made by the chosen methodology were evaluated. A clinical trial was conducted in six healthy individuals using a single DPI capsule containing 6 mg nano-AS DPI in lactose. Early blood bioavailability and atropinization pattern confirmed its value as a potential replacement to parenteral atropine in field conditions. The formulation seems to have the advantage of early therapeutic drug concentration in blood due to absorption through the lungs as well as sustained action due to absorption from the gut of the remaining portion of the drug.

Studies on in vitro and in vivo transdermal flux enhancement of methotrexate by a combinational approach in comparison to oral delivery.

BACKGROUND: Methotrexate (MTX) causes systemic toxicity thereby limiting its use; hence, transdermal delivery would be a possible alternative. METHOD: A comparative in vitro/in vivo study was done to see the effect of the two-tier system of chemical and physical enhancers. MTX was loaded into polyacrylamide-based hydrogel patch to see the effect of enhancers. RESULT: Flux enhancement (161%) of MTX was achieved when ternary mixture of ethyl acetate:menthol:ethanol (1:1:1) was used in combination with square-wave iontophoresis for 1 hour. Lower flux enhancement of 71%, 83%, and 93.5% was obtained in vitro with neat ethyl acetate, its binary composition with ethanol, and its ternary composition with ethanol and menthol, respectively, as compared to passive. However, with square-wave iontophoresis, it increased to 126%, 140%, and 161%, respectively. The mechanism of flux enhancement was supported by biophysical tools such as attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), and histopathology. ATR-FTIR studies demonstrated split in the asymmetric C-H vibration and amide II band with terpenes and iontophoresis, respectively. Additionally binary and ternary mixture of ethyl acetate demonstrated absence of ester peak accounting for lipid extraction. SEM of the skin samples treated with chemical enhancers in combination with square-wave iontophoresis showed both swelling and increased pore size of hair follicles, thus supporting higher permeation. Histopathological studies on treated skin samples of albino mice demonstrated epidermal thinning and focal disruptions, spongiosis, dermal edema, and appendageal dilatations. In vivo studies on mice demonstrated plasma concentration of 18.79 microg/mL with ternary mixture of ethyl acetate in combination with square wave, which is twofold higher to oral delivery. The reversibility studies conducted in vivo on mice demonstrated that the histological changes induced by the above-mentioned enhancers were transient and reversible in 48 hours. CONCLUSION: The above results indicate that the above-mentioned enhancers are safe and well tolerated by the skin.

Gelatin microspheres of rifampicin cross-linked with sucrose using thermal gelation method for the treatment of tuberculosis.

Oral controlled release microspheres of rifampicin (RIF) were prepared in order to circumvent the required regular high dose of the conventional dosage forms for the treatment of tuberculosis. Rifampicin containing microspheres were designed by using a biodegradable and biocompatible polymer, gelatin B, using a thermal gelation method. The microspheres were cross-linked with natural cross-linker, sucrose, to avoid the toxicities due to the synthetic di- and poly-aldehydes. This formulation was found to be controlled release for drug in the gastro-intestinal tract. Drug encapsulation efficiency was found to be in the range of 52-83%. These microspheres were characterized for; particle size analysis by optical microscopy and scanning electron microscopy; in vitro release study by USP paddle apparatus and drug polymer interaction study using DSC and FT-IR. The results suggested that microspheres prepared by the above method were smaller in size, i.e. less than 60 microm and sucrose could be used as an interesting means to cross-link gelatin B microspheres, allowing the use of this formulation for controlled release of rifampicin. Microspheres could be observed in the intestinal lumen at 4 h and were detectable in the intestine 24 h post-oral administration, although the percentage of radioactivity had significantly decreased (t(1/2) of (99m)Tc = 4-5 h). Dissolution and scintigraphy studies have shown promising results, proving the utility of the formulation for the whole intestine.

Nanocarrier for the transdermal delivery of an antiparkinsonian drug.

The purpose of the present study was to investigate the potential of nanoemulsions as nanodrug carrier systems for the percutaneous delivery of ropinirole. Nanoemulsions comprised Capryol 90 as the oil phase, Tween 20 as the surfactant, Carbitol as the cosurfactant, and water as an external phase. The effects of composition of nanoemulsion, including the ratio of surfactant and cosurfactant (Smix) and their concentration on skin permeation, were evaluated. All the prepared nanoemulsions showed a significant increase in permeation parameters such as steady state flux (Jss) and permeability coefficient (Kp) when compared to the control (p<0.01). Nanoemulsion composition (NEL3) comprising ropinirole (0.5% w/w), Capryol 90 (5% w/w), Smix 2:1 (35% w/w), and water (59.5% w/w) showed the highest flux (51.81+/-5.03 microg/cm2/h) and was selected for formulation into nanoemulsion gel. The gel was further optimized with respect to oil concentration (Capryol 90), polymer concentration (Carbopol), and drug content by employing the Box-Behnken design, which statistically evaluated the effects of these components on ropinirole permeation. Oil and polymer concentrations were found to have a negative influence on permeation, while the drug content had a positive effect. Nanoemulsion gel showed a 7.5-fold increase in skin permeation rate when compared to the conventional hydrogel. In conclusion, the results of the present investigation suggested a promising role of nanoemulsions in enhancing the transdermal permeation of ropinirole.

Oral bioavailability enhancement of exemestane from self-microemulsifying drug delivery system (SMEDDS).

Limited aqueous solubility of exemestane leads to high variability in absorption after oral administration. To improve the solubility and bioavailability of exemestane, the self-microemulsifying drug delivery system (SMEDDS) was developed. SMEDDS comprises of isotropic mixture of natural or synthetic oil, surfactant, and cosurfactant, which, upon dilution with aqueous media, spontaneously form fine o/w microemulsion with less than 100 nm in droplet size. Solubility of exemestane were determined in various vehicles. Ternary phase diagrams were plotted to identify the efficient self-emulsification region. Dilution studies, droplet size, and zeta potential of the formulations were investigated. The release of exemestane from SMEDDS capsules was studied using USP dissolution apparatus in different dissolution media and compared the release of exemestane from a conventional tablet. Oral pharmacokinetic study was performed in female Wistar rats (n = 8) at the dose of 30 mg kg(-1). The absorption of exemestane from SMEDDS form resulted in about 2.9-fold increase in bioavailability compared with the suspension. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as exemestane by the oral route.

Antimicrobial activity of a novel polyherbal combination for the treatment of vaginal infection.

The present study evaluated the antimicrobial activity of Azadirachta indica (AI), Cichorium intybus (CI), and Trigonella foenum-graecum (TFG) against bacterial and fungal pathogens responsible for the vaginal infections. The AI, CI, and TFG were selected to include antimicrobial and antifungal action against wide range of microbes. The different extracts of the herbs were evaluated for antibacterial and antifungal activity by well diffusion assays. Based on the results, the combination was selected and evaluated, "polyherbal antimicrobial (PHA)." The developed PHA extract demonstrated synergistic broad-spectrum antimicrobial activities including antibacterial and antifungal activity (minimum inhibition concentration: 5-7 mg/ml).

Recent approaches for the treatment of periodontitis.

Periodontal disease is a localised inflammatory response caused by the infection of a periodontal pocket arising from the accumulation of subgingival plaque. Periodontal disease has been considered as a possible risk factor for other systemic diseases such as cardiovascular diseases and pre-term low birth weight infants. Advances in understanding the aetiology, epidemiology and microbiology of periodontal pocket flora have revolutionised the therapeutic strategies for the management of periodontal disease progression. This review summarises the recent developments in the field of intra-pocket drug delivery systems and identifies areas where further research may lead to a clinically effective intra-pocket delivery system.

Solid self-nanoemulsifying delivery systems as a platform technology for formulation of poorly soluble drugs.

New drug discovery programs produce molecules with poor physico-chemical properties, making delivery of these molecules at the right proportion into the body a big challenge to the formulation scientist. The various options available to overcome the hurdle include solvent precipitation, micronisation/nanonization using high-pressure homogenization or jet milling, salt formation, use of microspheres, solid dispersions, cogrinding, complexation, and many others. Self-nanoemulsifying systems (SNES) form one of the most popular and commercially viable approaches for delivery of poorly soluble drugs exhibiting dissolution rate limited absorption, especially those belonging to the Biopharmaceutics Classification System II/IV. SNES are essentially an isotropic blend of oils, surfactants, and/or cosolvents that emulsify spontaneously to produce oil in water nanoemulsion when introduced into aqueous phase under gentle agitation. Conventional SNES consist of liquid forms filled in hard or soft gelatin capsules, which are least preferred due to leaching and leakage phenomenon, interaction with capsule shell components, handling difficulties, machinability, and stability problems. Solidification of these liquid systems to yield solid self-nanoemulsifying systems (SSNES) offer a possible solution to the mentioned complications, and that is why these systems have attracted wide attention. Other than the advantages and wide application of SSNEDS, the present paper focuses on formulation considerations, selection, and function of solidifying excipients; techniques of preparation; and case studies of drugs selected from different therapeutic categories. Developments in the techniques for in vitro evaluation of SSNEDS have also been discussed.

Pre-clinical evidence for altered absorption and biliary excretion of irinotecan (CPT-11) in combination with quercetin: possible contribution of P-glycoprotein.

P-glycoprotein (P-gp) is found to play a very significant role in intestinal and biliary transport of irinotecan and its active metabolite, SN-38. This makes P-gp inhibition a logical strategy for improving irinotecan's oral efficacy and reducing its toxicity. The objective of the present study was to identify the most suitable P-gp inhibitor, amongst various commonly used herbal components via in vitro screening; followed by determination of in vivo effects in rats. Caco-2 cell monolayers were used to investigate the influence of various components (quercetin, hesperitin, piperine, curcumin and naringenin) on the transport of irinotecan. The secretory transport (basolateral-to-apical) was significantly decreased by all components (p<0.05) except piperine. In the apical-to-basolateral transport, quercetin showed the highest absorptive permeability enhancement and P-gp interaction potential making it an appropriate candidate for further in vivo studies in female Wistar rats. Quercetin pre-treatment resulted in increased irinotecan C(max) and area under curve (AUC) with a concomitant decrease in t(max), plasma clearance and volume of distribution (p<0.05). The absolute bioavailability (F) of irinotecan control was 33%, which was increased to 43% (1.3 fold) by quercetin administration. The amounts of irinotecan and SN-38 eliminated in bile in control rats, is reduced to almost half when treated with quercetin. Our studies not only propose a safe approach for bioavailability enhancement and reducing toxicity of irinotecan by P-gp inhibition but in another way also reiterate the significance of elucidating herb-drug interactions for future insights.

Effective insulin delivery using starch nanoparticles as a potential trans-nasal mucoadhesive carrier.

Mucoadhesive nanoparticles (NPs) could be an exciting prospect for trans-nasal insulin delivery as they have higher surface area to cover highly vascularised nasal absorptive area providing a greater concentration gradient; hence the present study makes an attempt in this regard. Starch NPs were prepared by different crosslinkers using various methodologies and were loaded with insulin. Emulsion crosslinked particles were smaller in size compared to gel method (351 vs 997 nm), and size is further reduced when epichlorohydrin is used as crosslinking agent compared to POCl3 (194 vs 810 nm). NPs of epichlorohydrin emulsion were further optimized with variable crosslinking to evaluate the effect of degree of crosslinking on in vivo performance. In vitro, a size dependent first order diffusion controlled insulin release with an initial burst effect was found, which is higher with NPs of small size and least crosslinking. Formulation of EE-NPs with Na glycocholate showed a superior hypoglycemic action compared to other NPs formulations containing the former and lysophosphatidylcholine as permeation enhancers. The hypoglycemic effects were more pronounced with medium crosslinked NPs (EE-L2-NPs), which showed a nadir of 70% reduction of plasma glucose and significant effects until 6h. The peak plasma insulin level (Cmax) of medium crosslinked EE-L2-NPs (258 muIU/ml at 1h) vindicates the pharmacodynamic effect, which was found to be superior compared to all other formulations. The release rate and higher associated surface area might work in tandem, and could be greatly amplified when combined with permeation enhancers to make starch NPs an efficient trans-nasal mucoadhesive carrier of insulin.