Spanlastics: a novel elastic drug delivery system with potential applications via multifarious routes of administration.

Drug delivery systems (DDS) based on nanocarriers are designed to transport therapeutic agents to specific areas of the body where they are required to exhibit pharmacodynamic effect. These agents rely on an appropriate carrier to protect them from rapid degradation or clearance and enhance their concentration in target tissues. Spanlastics, an elastic, deformable surfactant-based nanovesicles have the potential to be used as a drug delivery vehicle for wide array of drug molecules. Spanlastics are formed by the self-association of non-ionic surfactants and edge activators in an aqueous phase and have gained attention as promising drug carriers due to their biodegradable, biocompatible, and non-immunogenic structure. In recent years, numerous scientific journals have published research articles exploring the potential of spanlastics to serve as a DDS for various types of drugs as they offer targeted delivery and regulated release of the drugs. Following brief introduction to spanlastics, their structure and methods of preparation, this review focuses on the delivery of various drugs using spanlastics as a carrier via various routes viz. topical, transdermal, ototopical, ocular, oral and nasal. Work carried out by various researchers by employing spanlastics as a carrier for enhancing therapeutic activity of different moieties has been discussed in detail.

Levofloxacin loaded clove oil nanoscale emulgel promotes wound healing in Pseudomonas aeruginosa biofilm infected burn wound in mice.

Owing to their tolerance to antibiotics, bacterial biofilms continue to pose a threat to mankind and are leading cause for non-healing of burn wounds. Within the biofilm matrix, antibiotics become functionally inactive due to restricted penetration and enzymatic degradation leading to rise of antimicrobial resistance. The objective of present investigation was to develop and characterize levofloxacin (LFX) loaded clove oil nanoscale emulgel (LFX-NE gel) and evaluate its in vivo therapeutic efficacy in Pseudomonas aeruginosa biofilm infected burn wound in mice. The optimized emulgel was found to possess good texture profile and showed shear thinning behavior. In vitro release study demonstrated complete drug release in 8 h and emulgel was found to be stable for 3 months at 25 °C and 40 °C. In vivo study revealed biofilm dispersal, complete wound closure, re-epithelialization and collagen deposition by LFX-NE gel in comparison to various control groups. LFX-NE gel was able to clear the infection within 7 days of treatment and promote wound healing as well. Therefore, administration of LFX-incorporated NE gel could be a beneficial treatment strategy for P. aeruginosa biofilm-infected burn wounds.

Engineered Site-specific Vesicular Systems for Colonic Delivery: Trends and Implications.

Steering drug-loaded, site-specific, coated lipid vesicles to the target receptor sites have the potential of plummeting adverse effects and improving the pharmacological response in diverse pathologies of the large bowel, especially the colon. Colonic delivery via oral route has its own challenges, often governed by several glitches such as drug degradation or absorption in the upper GIT, instability of proteins/peptides due to high molecular weight, and peptidase activity in the stomach. Consequently, colon-specific coated liposomal systems (CSLS) offer a potential alternate for not only site-specificity, but protection from proteolytic activity, and prolonged residence time for greater systemic bioavailability. On the other hand, liposomal delivery via the oral route is also cumbersome owing to several barriers such as instability in GIT, difficulty in crossing membranes, and issues related to production at the pilot scale. New advancements in the field of CSLS have successfully improved the stability and permeability of liposomes for oral delivery via modulating the compositions of lipid bilayers, adding polymers or ligands. Despite this ostensible propitiousness, no commercial oral CSLS has advanced from bench to bedside for targeted delivery to the colon as yet. Nevertheless, CSLS has quite fascinated the manufacturers owing to its potential industrial viability, simplistic and low-cost design. Hence, this review aims to decipher the convolutions involved in the engineering process of industrially viable CSLS for colonic delivery.

In Situ Forming Depot as Sustained-Release Drug Delivery Systems.

In situ forming systems can serve as promising alternative to existing long acting injectables like disperse systems and microspheres, owing to their biocompatibility, stability, ease of administration and scale up. Microspheres based on long-acting parenteral systems pose challenges in scaling up and process changes with the drug and polymer selected. In situ gelling systems are having low viscosity which is very conducive during various manufacturing unit operations and passing the formulation through hypodermic needle with lower applied pressure. Different mechanisms such as physical or physiological stimuli and cross linking reactions are involved in the gelling of in situ forming systems at the site of injection. Drug release from in situ forming systems can be altered according to the need by using different polymers, lipids and fatty acids. In situ forming systems can be evaluated by sol-gel transition time, temperature and pH, rheology, gel strength, texture analysis, syringeability and injectability. The present paper is an overview of the various in situ gelling polymers and their application in the preparation of depot formulations. Numerous products based on in situ forming systems such as Eligard®, Atridox® are available in market.

A New Therapeutic Approach for Brain Delivery of Epigallocatechin Gallate: Development and Characterization Studies.

BACKGROUND: Blood-brain permeability is the primary concern when dealing with the biodistribution of drugs to the brain in neurological diseases. OBJECTIVE: The purpose of the study is to develop the nanoformulation of Epigallocatechin gallate (EGCG) in order to improve its bioavailability and penetration into the brain. METHODS: EGCG loaded Solid Lipid Nanoparticles (SLNs) have been developed using microemulsification method and pharmacological assessments were performed. RESULTS: Surface morphology and micromeritics analysis showed the successful development of EGCG loaded solid lipid nanoparticles with an average size of 162.4 nm and spherical in shape. In vitro release studies indicated a consistent and slow drug release. Pharmacological evaluation of SLN-EGCG demonstrated a significant improvement in cerebral ischemia-induced memory impairment. CONCLUSION: The results indicate that the EGCG loaded SLNs provide a potential drug delivery system for improved delivery of EGCG to the brain, hence, enhancing its brain bioavailability.

Enhancement of In Vivo Efficacy and Oral Bioavailability of Aripiprazole with Solid Lipid Nanoparticles.

Aripiprazole (ARP), a second-generation or atypical antipsychotic, is poorly soluble and undergoes extensive hepatic metabolism and P-glycoprotein efflux which lead to reduced in vivo efficacy and increased dose-related side effects. To enhance in vivo efficacy and oral bioavailability of aripiprazole, aripiprazole-loaded solid lipid nanoparticles (SLNs) were developed using tristearin as solid lipid. Tween 80 and sodium taurocholate were used as surfactants to prepare SLNs using microemulsification method. SLNs were characterized for particle size, zeta potential, entrapment efficiency, and crystallinity of lipid and drug. In vitro release studies were performed in water containing 0.5% sodium dodecyl sulfate. Pharmacodynamic evaluation was carried out in laca mice using dizocilpine-induced schizophrenic model where behavioral evaluation revealed better in vivo efficacy of SLNs. Pharmacokinetics of aripiprazole-loaded SLNs after oral administration to conscious male Wistar rats was studied. Bioavailability of aripiprazole was increased 1.6-fold after formulation of aripiprazole into SLNs as compared to plain drug suspension. The results indicated that solid lipid nanoparticles can improve the bioavailability of lipophilic drugs like aripiprazole by enhancement of absorption and minimizing first-pass metabolism.

Liquid Nanosize Emulsion-Filled Enteric-Coated Capsules for Colon Delivery of Immunosuppressant Peptide.

Present study aims at solubilizing slightly water-soluble peptide into a nanosize emulsion which is filled into a hard gelatin capsule in the form of preconcentrate. Further, liquid-filled capsule was dip-coated with ethyl cellulose and Eudragit S100 for colon targeting. An in vitro release profile was studied for selected formulations, i.e., Formulation A (5 mg ethyl cellulose and 40 mg Eudragit S100), Formulation B (10 mg ethyl cellulose and 30 mg Eudragit S100), and Formulation C (10 mg ethyl cellulose and 20 mg Eudragit S100). Formulations B and A showed an immediate release after 5 and 6 h, respectively, which represents ileo-ceacal transit time. The nanosize of emulsion, i.e., below 100 nm, was confirmed by transmission electron microscopy. Also, a phase transition of nanosize emulsion from water in oil to oil in water on dilution with water was observed through TEM. This novel approach of filling poorly water-soluble protein in solubilized form of nanosize emulsion preconcentrate into coated hard gelatin capsules for colon targeting has been reported first time. This approach could be a breakthrough for the better management of local intestinal pathologies.

Evaluation of Ocular Irritation and Bioavailability of Voriconazole Loaded Microemulsion.

BACKGROUND: Voriconazole (VCZ), a second-generation antifungal with excellent attributes like, broad-spectrum activity, targeted delivery, and tolerability. VCZ loaded microemulsion could be an effective strategy for efficient ocular delivery of the drug. OBJECTIVE: To perform corneal irritation studies and in vivo delivery of VCZ microemulsion to establish its potential as an efficient ocular delivery system. METHODS: Ocular irritancy was performed by HETCAM (Hen's Egg Test Chorio Allantoic Membrane) assay, corneal histopathology and Draize test. Ex vivo and in vivo studies were performed to determine permeation efficiency of VCZ microemulsion. RESULTS: The irritation studies suggested the non-irritant nature of the microemulsion. The ex vivo studies performed on excised cornea displayed significant enhancement in drug permeation/penetration from microemulsion in contrast to the drug suspension. Further, the in vivo study confirmed the higher availability of VCZ (from microemulsion) in aqueous humor with minimal nasolacrimal drainage (lower plasma drug content) when compared with the drug suspension. CONCLUSION: The non-irritant nature and high corneal permeation of VCZ encourages the role of microemulsion as a potential ocular delivery system.

Effect of mesenchymal stem cells and galantamine nanoparticles in rat model of Alzheimer's disease.

AIM: The present study investigated the efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in combination with galantamine hydrobromide-loaded solid lipid nanoparticles (GH-SLNs) in intracerebroventricular (ICV)-isoproterenol-induced rat model of Alzheimer's disease. MATERIALS & METHODS: BM-MSCs were harvested by dissecting femur and tibia of 8-10-week-old Wistar rats. 1 × 10(6) cells were administered intravenously once in ICV-isoproterenol-induced rats followed by GH-SLNs (5 mg/kg) for 3 weeks. RESULTS & CONCLUSION: ICV-isoproterenol resulted in significant memory deficit. The results demonstrated rapid regain of memory in isoproterenol-induced amnesic rats, following single intravenous administration of BM-MSCs and oral administration of GH-SLNs for 21 days. The combination of BM-MSCs and GH-SLNs produced a more pronounced protective effect, therefore, could be explored for the management of Alzheimer's disease.

Solid lipid nanoparticle: an efficient carrier for improved ocular permeation of voriconazole.

This research focuses on the fabrication and evaluation of solid lipid nanoparticles (SLNs) for improved ocular delivery of voriconazole (VCZ). Compritol and palmitic acid were selected as lipid carriers based on drug solubility and partitioning behavior. Poloxamer and soya lecithin were the choice for surfactant, while sodium taurocholate was used as a co-surfactant. The particle sizes of the SLNs determined by zetasizer and transmission electron microscopy (TEM) were found within the desired range. The in vitro release study of SLNs exhibited a sustained-release property of the drug. The ex vivo studies displayed enhanced corneal drug permeation from SLNs in comparison to the drug suspension. Further, the corneal hydration studies, histopathology and Hen's Egg Test Chorio Allantoic Membrane (HETCAM) assay confirmed the non-irritancy of the nano-formulation. The in vivo study confirmed the higher availability of VCZ (from SLN) in aqueous humor with minimal nasolacrymal drainage in contrast to the drug suspension. A good in-vitro in-vivo correlation (IVIVC) further confirmed the potential of SLN as an effective carrier for ocular delivery.

Emerging Potential of Nanosuspension-Enabled Drug Delivery: An Overview.

Poor aqueous solubility is one of the key concerns of the majority of new drug molecules. One of the important problems associated with such drugs is that they often lead to low bioavailability. Researchers have used various techniques, but little success has been achieved due to poor stability and industrial viability, including technique cost. Of the numerous techniques, nanosuspensions (NSs) have drawn interest in improving solubility. NSs are dispersions of nanosized drug particles stabilized with the aid of appropriate agents. Stabilizers for NSs are generally recognized as safe (GRAS) excipients that can be chosen from a number of surfactants and/or polymers to food proteins. The commonly used techniques for preparation of NSs including top-down and bottom-up methods, along with new fabrication techniques based on supercritical (SC) fluids, are reviewed. This review also includes preparatory techniques, characterization, potential applications, and recent advancements in the field of NSs.

Design, Development and Characterization of Topical Microemulsions of 5-Fluorouracil for the Treatment of Non Melanoma Skin Cancer and its Precursor Lesions.

Treatment of non melanoma skin cancer and its precancerous skin lesions is associated with severe topical and systemic toxicity. So, it has become necessary to develop an efficient novel delivery system with less side effects and better patient compliance. Topical w/o microemulsion of 5-FU were prepared using sorbitan monooleate (Span 80), sorbitan trioleate (Span 85), polysorbate 80 (Tween 80), isopropyl alcohol (IPA) with different oils such as oleic acid, triacetin and isopropyl myristate (IPM). Evaluation tests of microemulsions like determination of thermodynamic stability, droplet size, viscosity, pH, conductivity and ex vivo release studies were performed. Spherical shape and Droplet size of microemulsion, which was around 100nm, was supported by Transmission electron microscopy. The lesser flux across skin for all microemulsion batches and higher skin retention of 5-FU loaded in microemulsion in comparison to topical 5-FU marketed cream resulted in better control over the drug release. Skin irritation studies on rats were performed to evaluate chronic toxicity of optimized microemulsion formulation on skin for 21 days and were compared with control group. Formalin (0.8%) was taken as standard irritant. Rat skin was observed for erythema and edema and the formulation was found safe for chronic use (p˃0.01). Histopathology studies showed the epidermal and dermal layers to be normal, showing the 5-FU microemulsion formulation to be safe for topical use. Better control of the drug release through skin can curtail topical and systemic toxicity which is supported by the skin irritation and histopathology studies.

Pioglitazone hydrochloride: chemopreventive potential and development of site-specific drug delivery systems.

The aim of this study was to investigate the potential of pioglitazone hydrochloride as a promising anticancer agent and then to design and evaluate the colon-targeted delivery system. The role of pioglitazone hydrochloride as a promising anticancer agent was evaluated by in vitro cell line studies and in vivo 1,2-dimethylhydrazine-induced colon carcinogenesis in rats. In order to deliver the drug at site of action, i.e. colon, drug embedded in matrices containing a release retarding polymer (HPMC K4M) and a polysaccharide (locust bean gum) were prepared. These matrix systems were further enteric coated with Eudragit®S100 to minimize the premature drug release in the upper segments of the GIT. In vitro dissolution studies were performed in absence and presence of rat caecal contents on selected batches and samples were analyzed using a validated RP-HPLC method. Hence, the studies led to the conclusion that successful site-specific delivery systems of pioglitazone hydrochloride were developed to improve its therapeutic efficacy in the management of colorectal cancer.

Emergence of nanomedicine as cancer targeted magic bullets: recent development and need to address the toxicity apprehension.

Multi drug resistance and non specific targeting is a major problem with conventional therapy. To overcome this problem, nanoparticles (NPs) have emerged as an important tool to deliver conventional drugs, recombinant proteins, vaccines and more recently, nucleotides. NPs modify the drug release pattern, absorption, distribution, metabolism, excretion (ADME) and therapeutic response. This review focuses on the potential of nanotechnology in cancer and discusses the different nanoparticulate drug-delivery systems including quantum dot, iron oxide nanoparticles, gold nanoparticles, carbon nanotubes, silica nanoparticles, dendrimer, graphene and polymeric nanoparticles with their applications in therapeutics, diagnostics, and imaging pattern. Further, the recent development and progress of theranostic nanoparticles in the treatment of cancer and toxicity associated with nanoparticles is also covered here.

Utility of an oxidation reaction for the spectrophotometric determination of acarbose in controlled release tablets at various simulated gastrointestinal media.

A sensitive kinetic method for spectrophotometric determination of acarbose is developed and validated for the determination of the drug in bulk and pharmaceutical formulations. The drug was estimated in simulated gastrointestinal media i.e., 0.1 M HCl (pH 1.2) and phosphate buffer (pH 6.8). The method involves the oxidation of acarbose by treating it with a strong oxidizing agent (potassium permanganate (1 x 10(-2) M)) in alkaline media. The reaction kinetics was determined for 20 min at room temperature. The reaction followed first order kinetics and the absorbance of the corresponding manganate ions produced was determined at 610 nm. The absorbance-concentration plot was found to be rectilinear over the concentration range of 2-20 microg/mL. The proposed method was used for estimation of the drug in a novel controlled release dosage form. Thus, the method developed was simple, reproducible and can be successfully applied for the determination of the drug in simulated gastrointestinal fluid.

Newer insights into the drug delivery approaches of α-glucosidase inhibitors.

INTRODUCTION: α-Glucosidase inhibitors (AGIs) are an important category of oral antidiabetic agents being extensively exploited for the effective management of type 2 diabetes and associated disorders. These drugs significantly reduce the postprandial rise in glycemic and plasma insulin levels both in nondiabetics and in type 2 diabetic patients. Currently only three drugs belonging to this category, viz, acarbose, miglitol and voglibose are in the market. The major limitations associated with the administration of AGIs are the stringent repetitive dosing schedule at specified time intervals, along with a high incidence of gastrointestinal disturbances that mainly include flatulence, abdominal distension, borborygmus and diarrhea. All these factors tend to decrease patient compliance. AREAS COVERED: This review focuses on the various formulation approaches being targeted for the effective delivery of AGIs, viz, unit matrix systems, bioadhesive pellets, hydrogels and lipid-based granules. EXPERT OPINION: It is concluded that development of a successful controlled-release delivery system for these drugs will obviate the need of repeated administration, which in turn will improve patient compliance.

A novel synergistic galactomannan-based unit dosage form for sustained release of acarbose.

In the current study, the potential of a novel combination of a galactomannan with acarbose (100 mg) was evaluated for attaining a desired hypoglycaemic effect over a prolonged period of time. Three major antidiabetic galactomannans viz., fenugreek gum, Boswellia gum, and locust bean gum were selected in order to achieve a synergistic effect in the treatment along with retardation in drug release. In vitro studies indicated that batches containing various proportions of fenugreek gum (AF40-60) were able to control drug release for a longer duration of approximately 10-12 h. In contrast, the matrices prepared using Boswellia and locust bean gum were able to sustain the release for relatively shorter durations. Drug release mainly followed first-order release kinetics owing to the highly soluble nature of the drug. In vivo study depicted a significant reduction (p < 0.001) in the postprandial blood glucose and triglyceride levels in the diabetic rats on treatment with formulation AF40. Thus, the developed system provides a better control of the postprandial glycaemic levels and it also obviates the need of conventional multiple dosing of acarbose. Furthermore, it also reduces the occurrence of side effects like diarrhea and loss of appetite.

Nanoemulsions as self-emulsified drug delivery carriers for enhanced permeability of the poorly water-soluble selective ß1-adrenoreceptor blocker Talinolol.

To enhance the bioavailability of the poorly water-soluble drug talinolol, a self-nanoemulsifying drug delivery system (SNEDDS) comprising 5% (w/v) Brij-721 ethanolic solution (Smix), triacetin, and water, in the ratio of 40:20:40 (% w/w) was developed by constructing pseudo-ternary phase diagrams and evaluated for droplet size, polydispersity index, and surface morphology of nanoemulsions. The effect of nanodrug carriers on drug release and permeability was assessed using stripped porcine jejunum and everted rat gut sac method and compared with hydroalcoholic drug solution, oily solution, and conventional emulsion and suspension. The SNEDDS showed a significant (P < 0.001) increase in drug release, permeability, and in vivo bioavailability as compared to drug suspension. This may be attributed to increased solubility and enhanced permeability of the drug from nanosized emulsion. FROM THE CLINICAL EDITOR: In this study, a self-nanoemulsifying drug delivery system was utilized to enhance the bioavailability of the poorly water-soluble beta-blocker talinolol. Significant increase in drug release, permeability, and in vivo bioavailability were demonstrated as compared to standard drug suspension.

Tailoring of drug delivery of 5-fluorouracil to the colon via a mixed film coated unit system.

The study was carried out to establish the effectiveness of a mixed film composed of ethylcellulose/Eudragit S100 for colonic delivery of 5-flourouracil (5-FU). Tablets cores containing 5-FU were prepared by direct compression method by coating at different levels (2-9%, m/m) with a non-aqueous solution containing ethylcellulose/Eudragit S100. Coated tablets were studied for the in vitro release of 5-FU and the samples were analyzed spectrophotometrically at 266 nm. Drug release from coated systems depended on the thickness of the mixed film and the composition of the core. Channel formation was initiated in the coat by dissolution of the Eudragit S100 fraction at higher pH in the colonic region. The release was found to be higher in tablets containing Avicel as filler owing to its wicking action compared to that from lactose containing cores. Furthermore, batches containing superdisintegrant (1%, m/m Cross-PVP) along with Avicel in the core released approximately 81.1% drug during the colonic transit time. Kinetic studies indicated that all the formulations followed first-order release kinetics. The developed delivery system will expectedly deliver the drug to the colon.

Molecular simulation of hydroxypropyl-beta-cyclodextrin with hydrophobic selective Cox-II chemopreventive agent using host-guest phenomena.

The present investigation outlays the host-guest penetration of hydrophobic selective Cox-II chemopreventive agent, celecoxib (CXB), with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) using inclusion complexation phenomena. Phase solubility studies conducted at 37 degrees C and 25 degrees C revealed typical A(L)-type curve for the HP-beta-CD indicating the formation of soluble complexes. The inclusion complexes in the molar ratio of 1:1 and 2:1 (CXB-HP-beta-CD) were prepared by kneading technique. The formation of inclusion complexes and the molecular simulation of CXB protons with HP-beta-CD cavity in all samples were testified by 1H-NMR, DSC, powder-XRD, SEM and FTIR and UV/visible spectroscopy. The results of these studies indicated that complex (prepared by kneading method) in molar ratio of 1:1 exhibited better improvement in in vitro dissolution profiles as compared to 1:2 complex. Mean in vitro dissolution time indicated significant difference in the release profiles of CXB from complexes and physical mixtures as compared to pure CXB.