Solid lipid nanoparticles as vesicles for oral delivery of olmesartan medoxomil: formulation,optimization and in vivo evaluation

Objective: Olmesartan medoxomil (OLM) is an antihypertensive drug with low oral bioavailability (28%) resulting from poor aqueous solubility, presystemic metabolism and P-glycoprotein mediated efflux. The present investigation studies the role of lipid nanocarriers in enhancing the OLM bioavailability through oral delivery.

Materials and methods: Solid lipid nanoparticles (SLN) were prepared by solvent emulsion-evaporation method. Statistical tools like regression analysis and Pareto charts were used to detect the important factors effecting the formulations. Formulation and process parameters were then optimized using mean effect plot and contour plots. The formulations were characterized for particle size, size distribution, surface charge, percentage of drug entrapped in nanoparticles, drug–excipients interactions, powder X-ray diffraction analysis and drug release in vitro.

Results and discussion: The optimized formulation comprised glyceryl monostearate, soya phosphatidylcholine and Tween 80 as lipid, co-emulsifier and surfactant, respectively, with an average particle size of 100?nm, PDI 0.291, zeta potential of ?23.4?mV and 78% entrapment efficiency. Pharmacokinetic evaluation in male Sprague Dawley rats revealed 2.32-fold enhancement in relative bioavailability of drug from SLN when compared to that of OLM plain drug on oral administration.

Conclusion: In conclusion, SLN show promising approaches as a vehicle for oral delivery of drugs like OLM.     

Formulation and optimisation of lamivudine‐loaded Eudragit® S 100 polymer‐coated pectin microspheres for colon‐specific delivery

This investigation is to find a prolonged or delayed drug release system, exclusively for the treatment of hepatitis‐B to reduce the side effects, which arise when conventional solid dose forms are administered. To pursue this goal, lamivudine‐loaded Eudragit‐coated pectin microspheres have been formulated employing water/oil (W/O) emulsion evaporation strategy. The formulation was optimised using a 3⁴ factorial design. A drug to polymer ratio of 1:2, the surfactant of 1 ml, the volume of 50 ml of processing medium with a stirring speed of 2500 rpm were found to be the optimal parameters to obtain the lamivudine‐loaded Eudragit‐coated pectin microspheres formulation with a high drug entrapment efficiency of 89.44% ± 1.44%. The in vitro release kinetics of lamivudine was a suitable fit to the Higuchi model, indicating a diffusion‐controlled release with anomalous transport. The obtained microspheres were then subjected to different characterisation studies, including scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X‐ray diffraction (XRD). The results of this study clearly indicate that Eudragit‐coated pectin microspheres could be the promising controlled release carriers for colon‐specific delivery of lamivudine in the presence of rat cecal content.     

Phyto‐fabrication,purification, characterisation,optimisation, and biological competence of nano‐silver

Published studies indicate that virtually any kind of botanical material can be exploited to make biocompatible, safe, and cost‐effective silver nanoparticles. This hypothesis is supported by the fact that plants possess active bio‐ingredients that function as powerful reducing and coating agents for Ag+. In this respect, a phytomediation method provides favourable monodisperse, crystalline, and spherical particles that can be easily purified by ultra‐centrifugation. However, the characteristics of the particles depend on the reaction conditions. Optimal reaction conditions observed in different experiments were 70–95 °C and pH 5.5–8.0. Green silver nanoparticles (AgNPs) have remarkable physical, chemical, optical, and biological properties. Research findings revealed the versatility of silver particles, ranging from exploitation in topical antimicrobial ointments to in vivo prosthetic/organ implants. Advances in research on biogenic silver nanoparticles have led to the development of sophisticated optical and electronic materials with improved efficiency in a compact configuration. So far, eco‐toxicity of these nanoparticles is a big challenge, and no reliable method to improve the toxicity has been reported. Therefore, there is a need for reliable models to evaluate the effect of these nanoparticles on living organisms.     

Docetaxel‐loaded solid lipid nanoparticles: a novel drug delivery system

Over the past few years, taxanes have emerged as a new class of anticancer drugs. Docetaxel (DTX) the prototype of this class has been approved for the treatment of broad range of cancers. However, to date the commercial preparation of DTX (Taxotere^®) is accompanying adverse side effects, intolerance, and poor solubility, which can be overcome by encapsulating them using solid lipid nanoparticles (SLNs). SLNs represent versatile delivery system of drugs with newer forms such as polymer–solid lipid hybrid, surface modified and long circulating nanoparticles bringing forth improved prospects for cancer chemotherapy. In this review, the authors have discussed the current uses of various SLNs formulations of DTX with key emphasis on controlled and site‐specific drug delivery along with enhanced antitumour activity elucidated via in vitro and in vivo studies. Furthermore, the review article highlights few approaches that can be used in combination with existing DTX‐loaded SLNs to supplement DTX drug delivery.Inspec keywords: nanoparticles, nanomedicine, drug delivery systems, biomedical materials, cancer, reviews, tumoursOther keywords: docetaxel‐loaded solid lipid nanoparticles, drug delivery system, taxanes, anticancer drugs, Taxotere, SLN encapsulation, polymer‐solid lipid hybrid, surface modified nanoparticles, long circulating nanoparticles, chemotherapy, review     

Liposome nano‐formulation with cationic polar lipid DOTAP and cholesterol as a suitable pH‐responsive carrier for molecular therapeutic drug (all‐trans retinoic acid) delivery to lung cancer cells

The molecular targeted drug ATRA demands a suitable carrier that delivers to the cancer site due to its poor bioavailability and drug resistance. ATRA, being a lipid with carboxylic acid, has been nano‐formulated as a cationic lipo‐ATRA with DOTAP:cholesterol:ATRA (5:4:1) and its pH‐responsive release, intracellular drug accumulation, and anticancer effect on human lung cancer (A549) cell line analysed. The analysis of the physicochemical characteristics of the developed lipo‐ATRA (0.8 µmol) revealed that the size of 231 ± 2.35 d.nm had a zeta potential of 6.4 ± 1.19 and an encapsulation efficiency of 93.7 ± 3.6%. The ATRA release from lipo‐ATRA in vitro was significantly (p ≤ 0.05) higher at acidic pH 6 compared to pH 7.5. The intracellular uptake of ATRA into lipo‐ATRA‐treated A549 cells was seven‐fold higher (0.007 ± 0.001 mg/ml) while only three‐fold uptake was observed in free ATRA treatment (0.003 ± 0.002 mg/ml). The lipo‐ATRA treatment caused a highly significant (p ≤ 0.001) decrease in percent cell viability at 48 h when compared with the free ATRA treatment. Overall, the results proved that the developed lipo‐ATRA has suitable physicochemical properties with enhanced ATRA release at acidic pH, while maintaining stability at physiologic pH and temperature. This resulted in an increased ATRA uptake by lung cancer cells with enhanced treatment efficiency. Hence, it is concluded that DOTAP lipo‐ATRA is a suitable carrier for ATRA delivery to solid cancer cells.     

Ketoconazole‐conjugated ZnO nanoparticles based semi‐solid formulation and study their impacts on skin disease

In this study, the ketoconazole‐conjugated zinc oxide (ZnO) nanoparticles were prepared in a single‐step approach using dextrose as an intermediate compound. The physical parameters confirmed the drug conjugation with ZnO and their size was around 70–75 nm. The drug loading and in vivo drug release studies indicated that the –CHO group from the dextrose increase the drug loading up to 65% and their release kinetics were also studied. The anti‐fungal studies indicated that the prepared nanoparticles exhibit strong anti‐fungal activity and the minimum concentration needed is 10 mg/ml. The nanoparticles loaded semi‐solid gel was prepared using carbopol, methylparaben, propyl paraben and propylene glycol. The in vitro penetration of the ketoconazole‐conjugated nanoparticles was studied using the skin. The results indicated that the semi‐solid gel preparations influenced the penetration and also favoured the accumulation into the skin membrane. The veterinary clinical studies indicated that the prepared gel is highly suitable for treatment of Malassezia.Inspec keywords: II‐VI semiconductors, skin, biomedical materials, antibacterial activity, wide band gap semiconductors, drug delivery systems, nanomedicine, drugs, diseases, gels, nanofabrication, nanoparticles, zinc compounds, biomembranes, veterinary medicineOther keywords: strong anti‐fungal activity, propyl paraben, propylene glycol, semisolid gel preparations, skin membrane, veterinary clinical studies, semisolid formulation, skin disease, ketoconazole‐conjugated zinc oxide nanoparticles, single‐step approach, physical parameters, drug conjugation, drug loading, release kinetics, dextrose, in vivo drug release studies, carbopol, methylparaben, in vitro penetration, Malassezia, ZnO     

Development of tamoxifen‐loaded surface‐modified nanostructured lipid carrier using experimental design: in vitro and ex vivo characterisation

The present study aimed to develop a surface‐modified biocompatible nanostructured lipid carrier (NLCs) system using polyoxyethylene (40) stearate (POE‐40‐S) to improve the oral bioavailability of poorly water‐soluble Biopharmaceutics Classification System class‐II drug like tamoxifen (TMX). Also aimed to screen the most influential factors affecting the particle size (PS) using Taguchi (L₁₂ (2¹¹)) orthogonal array design (TgL₁₂ OA). Then, to optimize the TMX loaded POE‐40‐S (P) surface‐modified NLCs (TMX‐loaded‐PEG‐40‐S coated NLC (PNLCs) or PNLCs) by central composite design (CCD) using a four‐factor, five‐level model. The most influential factors affecting the PS was screened and optimized. The in‐vitro study showed that increased drug‐loading (DL) and encapsulation efficiency (EE), decreased PS and charge, sustained drug release for the prolonged period of the time with good stability and suppressed protein adsorption. The Ex‐vivo study showed that decreased mucous binding with five‐fold enhanced permeability of PNLC formulation after surface modification with POE‐40‐S. The in‐vitro cytotoxicity study showed that the blank carrier is biocompatible and cytotoxicity of the formulation was dependent on the concentration of the drug. Finally, it can be concluded that the surface‐modified PNLCs formulation was an effective, biocompatible, stable formulation in the enhancement of dissolution rate, solubility, stability with reduced mucus adhesion and increased permeability thereby which indicates its enhanced oral bioavailability.Inspec keywords: nanoparticles, cellular biophysics, solubility, drug delivery systems, toxicology, adsorption, adhesion, dissolving, biomedical materials, encapsulation, polymers, proteins, nanomedicine, permeability, particle size, electrokinetic effectsOther keywords: water‐soluble BCS class‐II, TgL₁₂ OA, TMX‐loaded POE‐40‐S surface‐modified NLC, surface‐modified PNLC formulation, lipid‐based NLC system, oral bioavailability, stable formulation, biocompatible formulation, blank carrier, in vitro cytotoxicity, surface modification, PNLC formulation, drug release, central composite design, orthogonal array design, encapsulation efficiency, steric stabilisation effect, particle size, dissolution rate, polyoxyethylene stearate, surface‐modified biocompatible carrier system, systemic toxicity, water‐soluble drug, tamoxifen‐loaded surface‐modified nanostructured lipid carrier     

Chitosan nanoparticles for the oral delivery of tenofovir disoproxil fumarate: formulation optimization,characterization and ex vivo and in vivo evaluation for uptake mechanism in rats

Objective: Design chitosan based nanoparticles for tenofovir disoproxil fumarate (TDF) with the purpose of enhancing its oral absorption.

Significance: TDF is a prodrug that has limited intestinal absorption because of its susceptibility to gut wall esterases. Hence, design of chitosan based polymeric novel nanocarrier systems can protect TDF from getting metabolized and also enhance the oral absorption.

Methods: The nanoparticles were prepared using the ionic gelation technique. The factors impacting the particle size and entrapment efficiency of the nanoparticles were evaluated using design of experiments approach. The optimized nanoparticles were characterized and evaluated for their ability to protect TDF from esterase metabolism. The nanoparticles were then studied for the involvement of active transport in their uptake during the oral absorption process. Further, in vivo pharmacokinetic studies were carried out for the designed nanoparticles.

Results: The application of design of experiments in the optimization process was useful to determine the critical parameters and evaluate their interaction effects. The optimized nanoparticles had a particle size of 156?±?5?nm with an entrapment efficiency of 48.2?±?1%. The nanoparticles were well characterized and provided metabolic protection for TDF in the presence of intestinal esterases. The nanoparticles were able to increase the AUC of tenofovir by 380%. The active uptake mechanisms mainly involving clathrin-mediated uptake played a key role in increasing the oral absorption of tenofovir.

Conclusions: These results show the ability of the designed chitosan based nanoparticles in enhancing the oral absorption of TDF along the oral route by utilizing the active endocytic uptake pathways.     

Nanoparticles as tool for enhanced ophthalmic delivery of vancomycin: a multidistrict-based microbiological study,solid lipid nanoparticles formulation and evaluation

Context: A microbiological multidistrict-based survey from different Egyptian governorates was conducted to determine the most prevalent causative agents of ocular infections in the Egyptian population. Antibiotic sensitivity testing was then performed to identify the most potent antimicrobial agent. Vancomycin (VCM) proved the highest activity against gram-positive Staphylococcus bacteria, which are the most commonly isolated causative agents of ocular infection. However, topically applied VCM suffers from poor ocular bioavailability because of its high molecular weight and hydrophilicity. Objective: The aim of the present study was to develop VCM-loaded solid lipid nanoparticles (SLNs) using water-in-oil-in-water (W/O/W) double emulsion, solvent evaporation technique to enhance ocular penetration and prolong ophthalmic residence of VCM. Method: Two consecutive full factorial designs (2⁴ followed by 3²) were adopted to study the effect of different formulation and process parameters on SLN formulation. The lipid type and structure, polyvinyl alcohol (PVA) molecular weight and concentration, sonication time, as well as lipid:drug ratio were studied as independent variables. The formulated SLN formulae were evaluated for encapsulation efficiency (EE%), particle size (PS), and zeta potential as dependent variables. Results: The statistically-optimized SLN formula (1:1 ratio of glyceryltripalmitate:VCM with 1% low molecular weight PVA and 1?min sonication time) had average PS of 277.25?nm, zeta potential of ?20.45, and 19.99% drug encapsulation. Scanning and transmission electron micrographs showed well-defined, spherical, homogenously distributed particles. Conclusion: The present study suggests that VCM incorporation into SLNs is successfully achievable; however, further studies with different nanoencapsulation materials and techniques would be valuable for improving VCM encapsulation.     

Nanoethosomes for transdermal delivery of tropisetron HCl: multi-factorial predictive modeling,characterization, and ex vivo skin permeation

Objective: The aim of the present work is to exclusively optimize and model the effect of phospholipid type either egg phosphatidylcholine (EPC) or soybean phosphatidylcholine (SPC), together with other formulation variables, on the development of nano-ethosomal systems for transdermal delivery of a water-soluble antiemetic drug. Tropisetron HCl (TRO) is available as hard gelatin capsules and IV injections. The transdermal delivery of TRO is considered as a novel alternative route supposing to improve BAV as well as patient convenience.

Methods: TRO-loaded ethanolic vesicular systems were prepared by hot technique. The effect of formulation variables were optimized through a response surface methodology using 3?×?2²-level full factorial design. The concentrations of both PC (A) and ethanol (B) and PC type (C) were the factors, while entrapment efficiency (Y₁), vesicle size (Y₂), polydispersity index (Y₃), and zeta potential (Y₄) were the responses. The drug permeation across rat skin from selected formulae was studied. Particle morphology, drug–excipient interactions, and vesicle stability were also investigated.

Results: The results proved the critical role of all formulation variables on ethosomal characteristics. The suggested models for all responses showed good predictability. Only the concentration of phospholipid, irrespective to PC type, had a significant effect on the transdermal flux (p?Conclusion: The study suggests the applicability of statistical modeling as a promising tool for prediction of ethosomal characteristics. The ethanolic vesicles were considered as novel potential nanocarriers for accentuated transdermal TRO delivery.     

Fabrication of microcapsules with core‐shell structure for oral delivery of dual drugs and real‐time computed tomography imaging

Although multidrug combinations are an effective therapeutic strategy for serious disease in clinical practice, their therapeutic effect may be reduced because they conflict with each other medicinally in certain cases. Hence, there is an urgent need to develop a single drug carrier for precise multidrug delivery to avoid this interference. A reverse coordination method is reported that fabricates a double‐layer barium sulphate microcapsule (DL@BS MS) for two drugs separately loading simultaneously. In addition, BS nanoclusters were synthesised in situ inside the DL@BS MSs for real‐time computed tomography (CT) imaging. The results showed that the DL@BS MSs with a particle size of approximately 2 mm exhibited a uniform sphere. Because BS nanoclusters have a high X‐ray attenuation coefficient, the retention of DL@BS MSs in the digestive tract could be monitored through CT imaging in real time. More important, the core‐shell structure of DL@BS MSs encapsulating two different drugs could be released in spatiotemporal order in an acidic stomach environment. The as‐synthesis DL@BS MSs with a core‐shell structure and real‐time imaging performance provide an ideal carrier for the oral administration of multiple drugs simultaneously loaded but sequentially released.     

Lamivudine‐conjugated and efavirenz‐loaded G2 dendrimers: Novel anti‐retroviral nano drug delivery systems

Infection with human immunodeficiency virus (HIV)‐1 causes immunological disorders and death worldwide which needs to be further assisted by novel anti‐retroviral drug delivery systems. Consequently, finding newer anti‐retroviral pharmaceuticals by using biocompatible, biodegradable nanomaterials comprising a nanoparticle as core and a therapeutic agent is of high global interest. In this experiment, a second generation of a negatively charged nano‐biopolymer linear globular G2 dendrimer was carefully conjugated and loaded with well‐known anti‐HIV drugs lamivudine and efavirenz, respectively. They were characterised by a variety of analytical methods such as Zetasizer, Fourier‐transform infrared spectroscopy, elemental analysis and liquid chromatography‐mass spectroscopy. Additionally, conjugated lamivudine and loaded efazirenz with globular PEGylated G2 dendrimer were tested on an HEK293 T cell infected by single‐cycle replicable HIV‐1 virion and evaluated using XTT test and HIV‐1 P24 protein load. The results showed that lamivudine‐conjugated G2 significantly decreased retroviral activity without any cell toxicity. This effect was more or less observed by efavirenz‐loaded G2. These nano‐constructs are strongly suggested for further in vivo anti‐HIV assays.     

Solid lipid nanoparticles of anticancer drug andrographolide: formulation,in vitro and in vivo studies

Diterpenoidal anti-cancer drug andrographolide (AD) was encapsulated into solid lipid nanoparticle (SLN) because of poor aqueous solubility and high lipophilicity. AD-SLNs were prepared by solvent injection method and characterized for droplet size, surface morphology, zeta potential, etc. In vitro drug release was carried out by dialysis-membrane method. A pharmacokinetic study was performed by UPLC/Q-TOF-MS method to determine the maximum plasma concentration (C_max), area under the curve (AUC), etc. There was an improvement in C_max and AUC of AD-SLNs when compared with AD, thereby enhancing the bioavailability of AD. The t_max was increased than that of AD suspension, indicating the sustained release pattern of AD-SLNs. The antitumor activity was carried out on Balb/c mice showing better results with AD-SLNs as compared to AD. Thus, the AD-loaded SLNs would be useful for delivering poorly water-soluble AD with enhanced bioavailability and improved antitumor activity.     

DOC‐LS,a new liposome for dermal delivery,and its endocytosis by HaCaT and CCC‐ESF‐1 cells

The main objective of this work was to investigate the uptake channels of skin cells through which coumarin 6, transported by deoxycholate‐mediated liposomes (DOC‐LS), was internalised; this was also compared against the action of conventional LS. Coumarin 6‐loaded DOC‐LS and LS were characterised for size distribution, zeta potential, and shape, and analysed in vitro in human epidermal immortal keratinocyte (HaCaT) (epidermal) and human embryonic skin fibroblast (CCC‐ESF‐1) (dermal) cell lines. Various endocytosis inhibitors were incubated with cells treated with the nanocarriers. Flow cytometry results indicated that HaCaT and CCC‐ESF‐1 cells internalise the tested preparations through pinocytotic vesicles, macropinocytosis, clathrin‐mediated endocytic pathways, and via lysosomes, which consume a considerable amount of energy. The endocytosis pathways of DOC‐LS and LS showed no difference. This study provides a basis for the application of LS being combined with a microneedle system for efficient intracellular drug delivery, targeting cutaneous histocyte disorders.Inspec keywords: drugs, nanoparticles, lipid bilayers, nanomedicine, biomedical materials, electrokinetic effects, biomembrane transport, drug delivery systems, skin, organic compoundsOther keywords: dermal delivery, CCC‐ESF‐1 cells, skin cells, deoxycholate‐mediated liposomes, coumarin 6‐loaded DOC‐LS, endocytosis inhibitors, clathrin‐mediated endocytic pathways, endocytosis pathways, HaCaT cell lines, size distribution, zeta potential, nanocarriers, flow cytometry, pinocytotic vesicles, macropinocytosis, microneedle system, efficient intracellular drug delivery, targeting cutaneous histocyte disorders     

Anti-hyperuricemic property of 6-shogaol via self-micro emulsifying drug delivery system in model rats: formulation design,in vitro and in vivo evaluation

The prevalence of hyperuricemia is relatively high worldwide, and a great number of patients are suffering from its complications. 6-shogaol, an alkylphenol compound purified from the root of ginger (Zingiber officinale Roscoe), has been proved to possess diverse pharmacological activities. However, its poor aqueous solubility usually leads to low bioavailability, and further clinical applications will be greatly discounted. The current study aimed to formulate a 6-shogaol-loaded-Self Microemulsifying Drug Delivery System (SMEDDS) to amend low aqueous solubility and bioavailability orally, as well as, potentiate the hyperuricemic activity of the 6-shogaol. SMEDDS was developed with central composite design established on a two system components viz., 18.62% W/W ethyl oleate (oil phase) and ratio of tween 80 (surfactant) to PEG 400 (co-surfactant) (1.73:1, W/W). Based on quadratic model, the navigation of the design space could generate spherically-shaped and homogenous droplets with respective mean particle diameter, polydispersity and of 20.00?±?0.26?nm and 0.18?±?0.02. The 6-shogaol-SMEDDS showed significant elevation of cumulative release compared with the free 6-shogaol and more importantly a 571.18% increment in the relative oral bioavailability of the drug. The predominant accumulation of 6-shogaol-SMEDDS in the liver suggested hepatic-targeting potentiality of the drug. Oral administration of 6-shogaol-SMEDDS in hyperuricemic rats also significantly decreased uric acid level and xanthine oxidase activity. Histological studies confirmed formulation groups indeed could provide better protection of kidney than free drug groups. Collectively, these findings indicated that the SMEDDS hold much promise in enhancing the oral delivery and therapeutic efficacy of 6-shogaol.     

Sugar coated ceramic nanocarriers for the oral delivery of hydrophobic drugs: formulation, optimization and evaluation

In order to enhance the delivery of poorly-soluble drugs, we have explored aquasomes (three-layered, ceramic core based, oligosaccharide coated nanoparticles) as potential carriers for the delivery of model hydrophobic drug piroxicam (log P = 3.1). Ceramic nanoparticles were prepared using two techniques; namely, co-precipitation by refluxing and co-precipitation by sonication. Core preparation was finally done using sonication approach; based on the higher % yield (42.4 ± 0.4%) and shorter duration (1 day) compared to the reflux method (27.4 ± 2.05%, 6 days). Lactose loading onto ceramic core was achieved using adsorption. Colorimetric analysis of lactose coating was done using Anthrone method. Optimization of process variables namely, incubation time and core to coat ratio (for sugar loading) was carried out. Optimum time of incubation was 3 h and the core to coat ratio was 4:1. The drug loading was achieved by incubating the sugar loaded cores in different concentrations of piroxicam solution and it was found that 1.5% w/v piroxicam was optimal. Structural characterization using Fourier-Transform Infra Red Spectroscopy (FTIR) confirmed the presence of sugar coating onto the core. Morphological evaluation using transmission electron microscopy (TEM) revealed spherical nanoparticles (size 56.56 ± 5.93 nm for lactose coated core and 184.75 ± 13.78 nm for piroxicam loaded aquasomes) confirming the nanometric dimensions.     

Cubosomal based oral tablet for controlled drug delivery of telmisartan: formulation,in-vitro evaluation and in-vivo comparative pharmacokinetic study in rabbits

A nanoparticulate system; cubosomes has been suggested to support the controlled release of Telmisartan (TEL), a poorly water-soluble medication. Four distinctive formulae were selected according to the results of three estimated responses. The liquid cubosomes were successfully adsorbed onto Aerosil 380 to form granules. The formulae were evaluated for their flow properties. The best granules were compressed into tablets suitable for oral administration. The tablets were evaluated for its performance. The in vivo study of the best selected cubosomal tablets was checked after oral administration in the blood of albino rabbits utilizing an HPLC method. Results revealed that the highest EE was shown in formulae C5 (59.68?±?1.3). All the prepared formulae had particle size less than 500?nm with PDI < 0.5 and the highest zeta potential results were observed in C5, C7, C9, C11 and C12 (>30?mv). A7 and A9 prepared using Aerosil 380 showed a perfect flowability. After 1?h of dissolution testing, the commercial product showed a 66% drug release while the release of all cubosomal formulae didn’t exceed 35% during the first hour reaching a 85% of the drug released at the end of 24?h. A7 was selected for the in vivo study; T_max of TEL absorption is increased for cubosomal formula by three folds indicating sustained release pattern. The relative bioavailability is also increased by 2.6 fold. The investigation proposed the rationality of cubosome to figure an effective controlled release tablets to improve its bioavailability and expand its activity.     

Topical delivery of tetrahydrocurcumin lipid nanoparticles effectively inhibits skin inflammation: in vitro and in vivo study

Tetrahydrocurcumin (THC) also referred to as ‘white curcumin’, is a stable colorless hydrogenated product of curcumin with superior antioxidant and anti-inflammatory properties. The present study is an attempt to elevate the topical bioavailability of THC, post-incorporation into a nano-carrier system with its final dosage as a hydrogel. Lipid nanoparticles of THC (THC-SLNs) prepared by microemulsification technique were ellipsoidal in shape (revealed in transmission electron microscopy) with a mean particle size of 96.6?nm and zeta potential of ?22?mV. Total drug content and entrapment efficiency of THC-SLNs was 94.51%?±?2.15% and 69.56%?±?1.35%, respectively. Differential scanning calorimetry and X-ray diffraction studies confirmed the formation of THC-SLNs. In vitro drug release studies showed the drug release from THC-SLNs gel to follow Higuchi’s equation revealing a Fickian diffusion. Ex vivo permeation studies indicated a 17 times (approximately) higher skin permeation of THC-SLNs gel as compared with the free THC gel. Skin irritation, occlusion, and stability studies indicated the formulation to be nonirritating, and stable with a desired occlusivity. Pharmacodynamic evaluation in an excision wound mice model clearly revealed the enhanced anti-inflammatory activity of THC-SLNs gel and was further confirmed using biochemical and histopathological studies. It is noteworthy to report here that THC-SLNs gel showed significantly better (p?≤?0.001) activity than free THC in gel. As inflammation is innate to all the skin disorders, the developed product opens up new therapeutic avenues for several skin diseases. To the best of our knowledge, this is the first paper elaborating the therapeutic usefulness of white curcumin-loaded lipidic nanoparticles for skin inflammation.     

Preparation and characterisation of atorvastatin and curcumin‐loaded chitosan nanoformulations for oral delivery in atherosclerosis

Atorvastatin known to be a potential inhibitor of HMG‐CoA reductase involved in the synthesis of cholesterol. It is touted as miracle drug due to its profound effect in decreasing the low‐density lipoproteins in blood. Unfortunately, the high dosage used poses side‐effects relatively in comparison to other statins. On the other hand, curcumin has a diverse therapeutic potential in health and disease. However, the poor aqueous solubility and low bioavailability hinders the therapeutic potential of it when administrated orally. Therefore, it was thought to minimise the frequency of atorvastatin doses to avoid the possibility of drug resistance and also to overcome the limitations of curcumin for desirable therapeutic effects by using nanocarriers in drug delivery. In this investigation, synergistic effect of atorvastatin and curcumin nanocarriers was encapsulated by chitosan polymer. The chitosan nanocarriers prepared by ionic gelation method were characterised for their particle size, zeta potential, and other parameters. The drug‐loaded nanocarriers exhibited good encapsulation efficiency (74.25%) and showed a slow and sustained release of atorvastatin and curcumin 60.36 and 61.44%, respectively, in a span of 48 h. The drug‐loaded nanocarriers found to be haemocompatible and qualified for drug delivery in atherosclerosis.Inspec keywords: nanomedicine, drug delivery systems, diseases, cardiovascular system, enzymes, nanofabricationOther keywords: atorvastatin chitosan nanoformulation, curcumin‐loaded chitosan nanoformulation, oral delivery, atherosclerosis, potential inhibitor, HMG‐CoA reductase, cholesterol synthesis, miracle drug, low‐density lipoproteins, blood, diverse therapeutic potential, poor aqueous solubility, low bioavailability, drug resistance, nanocarriers, ionic gelation method, particle size, zeta potential, encapsulation efficiency     

Chitosan nanocapsules as carriers for oral peptide delivery: effect of chitosan molecular weight and type of salt on the in vitro behaviour and in vivo effectiveness

We have recently reported preliminary data showing the efficacy of chitosan nanocapsules as carriers for oral peptide delivery. In the present work, our aim was to investigate the influence of some chitosan properties, such as the molecular weight and type of salt, on the interaction of these nanocapsules with the Caco-2 cells and also on their in vivo effectiveness. Chitosan nanocapsules were prepared by the solvent displacement technique using high (450 kDa) and medium (160 kDa) molecular weight chitosan glutamate as well as high molecular weight chitosan hydrochloride (270 kDa). The results indicated that the size of the nanocapsules was dependent on the chitosan molecular weight, whereas the zeta potential and the association efficiency of salmon calcitonin were not affected by the chitosan properties. Upon incubation with the Caco-2 cells, chitosan nanocapsules exhibited a dose-dependent cellular viability, which was hardly affected by, either the chitosan molecular weight or, the type of salt. In addition, it was observed that the transepithelial electrical resistance of the Caco-2 monolayer was not significantly modified upon their exposure to chitosan nanocapsules. The results of the in vivo studies, following oral administration to rats, indicated that chitosan nanocapsules were able to reduce significantly the serum calcium levels, and to prolong this reduction for at least 24 hours, irrespective of the type of chitosan salt and molecular weight of chitosan. Consequently, the performance of chitosan nanocapsules as oral carriers for salmon calcitonin was not affected by the characteristics of chitosan.