Role of nanocarriers in photodynamic therapy.

Photodynamic therapy (PDT) is an important tool for the treatment of various cutaneous malignant and non-malignant diseases. This therapy involves the application of a photosensitizer to the affected area which is followed by illumination with the light of a particular wavelength resulting in the death of cancerous cells. This review encompasses a brief description of the mechanism of photodynamic therapy and different photosensitizers used clinically. However, the major obstacle with a majority of photosensitizers is its limited bioavailability and long-term photosensitivity which limits its use. To overcome these limitations different nanocarriers systems has been developed and studied for their efficacy in PDT, which forms the focal point of the review.

Recent Advances in Nanotherapeutic Interventions for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD), with impairment of learning and memory as the common clinical manifestations, is one of the most challenging diseases affecting individuals, their families and society as a whole. The fact that its prevalence is escalating rapidly, with the total number of AD patients estimated to reach 115.4 million by 2050, has made the disease a very challenging ailment worldwide. Several biological barriers like the bloodbrain barrier (BBB), drug efflux by P-glycoprotein and the blood-cerebrospinal fluid barrier restrict the delivery of conventional AD drugs to the central nervous system (CNS), thereby limiting their effectiveness. In order to overcome the above physiological barriers, the development of nanomedicines has been extensively explored. The present review provides an insight into the pathophysiology of AD and risk factors associated with AD. Besides, various nanoformulations reported in the literature for the diagnosis and treatments of AD have been classified and summarised. The patented nanoformulations for AD and details of nanoformulations which are in clinical trials are also mentioned. The review would be helpful to researchers and scientific community by providing them with information related to the recent advances in nanointerventions for the diagnosis and treatment of AD, which they can further explore for better management of the disease. However, although the nanotherapeutics for managing AD have been extensively explored, the factors which hinder their commercialisation, the toxicity concern being one of them, need to be addressed so that effective nanotherapeutics for AD can be developed for clinical use.

Ligand Conjugated Targeted Nanotherapeutics for Treatment of Neurological Disorders.

BACKGROUND: Human brain is amongst the most complex organs in human body, and delivery of therapeutic agents across the brain is a tedious task. Existence of blood brain barrier (BBB) protects the brain from invasion of undesirable substances; therefore it hinders the transport of various drugs used for the treatment of different neurological diseases including glioma, Parkinson's disease, Alzheimer's disease, etc. To surmount this barrier, various approaches have been used such as the use of carrier mediated drug delivery; use of intranasal route, to avoid first pass metabolism; and use of ligands (lactoferrin, apolipoprotein) to transport the drug across the BBB. Ligands bind with proteins present on the cell and facilitate the transport of drug across the cell membrane via. receptor mediated, transporter mediated or adsorptive mediated transcytosis. OBJECTIVE: The main focus of this review article is to illustrate various studies performed using ligands for delivering drug across BBB; it also describes the procedure used by various researchers for conjugating the ligands to the formulation to achieve targeted action. METHODS: Research articles that focused on the used of ligand conjugation for brain delivery and compared the outcome with unconjugated formulation were collected from various search engines like PubMed, Science Direct and Google Scholar, using keywords like ligands, neurological disorders, conjugation, etc. Results and Conclusion: Ligands have shown great potential in delivering drug across BBB for treatment of various diseases, yet extensive research is required so that the ligands can be used clinically for treating neurological diseases.

Role of Rutin Nanoemulsion in Ameliorating Oxidative Stress: Pharmacokinetic and Pharmacodynamics Studies.

Parkinson's disease is caused due to free radical generation in dopamine neurons leading to oxidative stress induced damage. The aim of this work was to ameliorate the free radical induced oxidative stress in rats by using TPGS (Tocopheryl polyethylene glycol 1000 succinate) loaded rutin nanoemulsion after oral administration. For this purpose, pharmacokinetic and pharmacodynamics studies were performed in albino wistar rats. Various behavioural tests (photoactometer test, rota rod, akinesia and catalepsy) and biochemical estimations for determination of GSH, TBARS and SOD were carried out. The results showed an increase in relative bioavailability of rutin after oral administration of nanoemulsion as compared to pure drug suspension. The AUC and Cmax of rutin nanoemulsion after oral administration were 1.8-fold and 1.9-fold higher than those of drug suspension respectively. Pharmacodynamic studies have shown good results with the rutin nanoemulsion than pure drug suspension. The rats treated with the rutin nanoemulsion exhibited significantly greater locomotor activity, better muscle coordination and improvement in cataleptic behaviour than the normal and haloperidol-induced rats (p < 0.001).Treatment with rutin suspension and rutin nanoemulsion helped in improving the stressed condition by increasing the levels of GSH, SOD and decrease in MDA levels in the brain. Anticancer activity was observed in a dose-dependent manner from 1 to 100 µg/ml. IC50 values for rutin suspension and rutin NE were found to be 36.7 and 25.4 µg/ml respectively. The rutin nanoemulsion has proven to be beneficial in ameliorating oxidative stress.

Nanoemulsions for Improved Efficacy of Phytotherapeutics- A Patent Perspective.

BACKGROUND: Phytoceuticals have been used extensively worldwide due to their reduced toxicity and therapeutic efficacy. The major drawback associated with their delivery which includes lack of sustained action and lipophilicity has been overcome by applications of scientific approach by scientists and researchers. Novel drug delivery systems aimed at enhancing bioavailability, reducing toxicity and in turn improving the patient compliance have been developed with success in recent times. Recent developments in the modern phytopharmaceutical research methods have also solved the major hurdles related to the extraction, identification of constituents in polyherbal systems, and standardisation thereby further facilitating the formulation of improved dosage forms like nanoemulsions with better efficacy of the herbal drugs. METHOD: We did extensive literature review, which included an in depth study and collection of both peer reviewed research and review manuscripts as well as patents related to phytonanoemulsions, which were included in the manuscript. RESULTS: In this article, an attempt has been made to compile the therapeutic and non therapeutic applications of herbal drugs formulated as nanoemulsions, patented phytonanoemulsions, with a discussion on the toxicity and future aspects of the nanoemulsion based delivery of phytotherapeutics. CONCLUSION: The findings of the review confirm that phytonanoemulsions are novel formulations which can be utilized both for therapeutic as well as nontherapeutic applications.

Synergistic antioxidant action of vitamin E and rutin SNEDDS in ameliorating oxidative stress in a Parkinson's disease model.

PURPOSE: Oxidative stress is the leading cause in the pathogenesis of Parkinson's disease. Rutin is a naturally occurring strong antioxidant molecule with wide therapeutic applications. It suffers from the problem of low oral bioavailability which is due to its poor aqueous solubility. METHODS: In order to increase the solubility self-nanoemulsifying drug delivery systems (SNEDDS) of rutin were prepared. The oil, surfactant and co-surfactant were selected based on solubility/miscibility studies. Optimization was done by a three-factor, four-level (34) Box-Behnken design. The independent factors were oil, surfactant and co-surfactant concentration and the dependent variables were globule size, self-emulsification time, % transmittance and cumulative percentage of drug release. The optimized SNEDDS formulation (RSE6) was evaluated for various release studies. Antioxidant activity was assessed by various in vitro tests such as 2,2-diphenyl-1-picrylhydrazyl and reducing power assay. Oxidative stress models which had Parkinson's-type symptoms were used to determine the antioxidant potential of rutin SNEDDS in vivo. Permeation was assessed through confocal laser scanning microscopy. RESULTS: An optimized SNEDDS formulation consisting of Sefsol + vitamin E-Solutol HS 15-Transcutol P at proportions of 25:35:17.5 (w/w) was prepared and characterized. The globule size and polydispersity index of the optimized formulation was found to be 16.08 ± 0.02 nm and 0.124 ± 0.01, respectively. A significant (p < 0.05) increase in the percentage of drug release was achieved in the case of the optimized formulation as compared to rutin suspension. Pharmacokinetic study showed a 2.3-fold increase in relative oral bioavailability. The optimized formulation had significant in vitro and in vivo antioxidant activity. CONCLUSION: Rutin SNEDDS have been successfully prepared and they can serve as an effective tool in enhancing the oral bioavailability and efficacy of rutin, thus helping in ameliorating oxidative stress in neurodegenerative disorders like Parkinson's disease.

Nanostructured lipid carrier in photodynamic therapy for the treatment of basal-cell carcinoma.

Topical photodynamic therapy (PDT) is a promising alternative for malignant skin diseases such as basal-cell carcinoma (BCC), due to its simplicity, enhanced patient compliance, and localization of the residual photosensitivity to the site of application. However, insufficient photosensitizer penetration into the skin is the major issue of concern with topical PDT. Therefore, the aim of the present study was to enable penetration of photosensitizer to the different strata of the skin using a lipid nanocarrier system. We have attempted to develop a nanostructured lipid carrier (NLC) for the topical delivery of second-generation photosensitizer, 5-amino levulinic acid (5-ALA), whose hydrophilicity and charge characteristic limit its percutaneous absorption. The microemulsion technique was used for preparing 5-ALA-loaded NLC. The mean particle size, polydispersity index, and entrapment efficiency of the optimized NLC of 5-ALA were found to be 185.2 ± 1.20, 0.156 ± 0.02, and 76.8 ± 2.58%, respectively. The results of in vitro release and in vitro skin permeation studies showed controlled drug release and enhanced penetration into the skin, respectively. Confocal laser scanning microscopy and cell line studies respectively demonstrated that encapsulation of 5-ALA in NLC enhanced its ability to reach deeper skin layers and consequently, increased cytotoxicity.

Chlorogenic acid stabilized nanostructured lipid carriers (NLC) of atorvastatin: formulation, design and in vivo evaluation.

The present work was aimed at developing an optimized oral nanostructured lipid carrier (NLC) formulation of poorly soluble atorvastatin Ca (AT Ca) and assessing its in vitro release, oral bioavailability and pharmacodynamic activity. In this study, chlorogenic acid, a novel excipient having synergistic cholesterol lowering activity was utilized and explored in NLC formulation development. The drug-loaded NLC formulations were prepared using a high pressure homogenization technique and optimized by the Box-Behnken statistical design using the Design-Expert software. The optimized NLC formulation was composed of oleic acid and stearic acid as lipid phase (0.9% w/v), poloxamer 188 as surfactant (1% w/v) and chlorogenic acid (0.05% w/v). The mean particle size, polydispersity index (PDI) and % drug entrapment efficiency of optimized NLC were 203.56 ± 8.57 nm, 0.27 ± 0.028 and 83.66 ± 5.69, respectively. In vitro release studies showed that the release of drug from optimized NLC formulations were markedly enhanced as compared to solid lipid nanoparticles (SLN) and drug suspension. The plasma concentration time profile of AT Ca in rats showed 3.08- and 4.89-fold increase in relative bioavailability of developed NLC with respect to marketed preparation (ATORVA® tablet) and drug suspension, respectively. Pharmacodynamic study suggested highly significant (**p < 0.01) reduction in the cholesterol and triglyceride values by NLC in comparison with ATORVA® tablet. Therefore, the results of in vivo studies demonstrated promising prospects for successful oral delivery of AT Ca by means of its chlorogenic acid integrated NLC.

Brain delivery of buspirone hydrochloride chitosan nanoparticles for the treatment of general anxiety disorder.

The present work discusses the preparation, characterization and in vivo evaluation of thiolated chitosan nanoparticles (TCS-NPs) of buspirone hydrochloride (BUH) for brain delivery through intranasal route. TCS NPs were prepared by ionic gelation method and characterized for various parameters. The NPs formed were having particle size of 226.7±2.52nm with PDI 0.483±0.031. Drug entrapment efficiency (EE) and loading capacity (LC) were found to be 81.13±2.8 and 49.67±5.5%. The cumulative percentage drug permeation through nasal mucosa was 76.21%. Bioadhesion study carried out on porcine mucin and showed a bioadhesion efficiency of 90.218±0.134%. Nose-to-brain delivery of placebo NPs was investigated by confocal laser scanning microscopy (CLSM) technique using rhodamine-123 as a marker. The brain concentration achieved after intranasal administration of TCS-NPs was 797.46±35.76ng/ml with tmax 120min which was significantly higher than achieved after intravenous administration on BUH solution 384.15±13.42ng/ml and tmax of 120min and intranasal administration of BUH solution 417.77±19.24ng/ml and tmax 60min.