Jasjeet Kaur Narang

Nanostructured lipid carriers: An emerging platform for improving oral bioavailability of lipophilic drugs

Nowadays exploration of novel lipid-based formulations is akin to a magnet for researchers worldwide for improving the in vivo performance of highly lipophilic drugs. Over the last few years, new compositions of lipids have been developed, and the probable bioavailability enhancement has been investigated. We reviewed the most recent data dealing with backlogs of conventional lipid-based formulations such as physical instability, limited drug loading capacities, drug expulsion during storage along with all the possible hindrances resulting in poor absorption of highly lipophilic drugs such as P-glycoprotein efflux, extensive metabolism by cytochrome P450 etc. In tandem with these aspects, an exclusive formulation approach has been discussed in detail in this paper. Therefore, this review focuses on resolving the concerned ambiguity with successful oral administration of highly lipophilic drugs through designing novel lipidic formulations (nanostructured lipid carriers [NLC]) that constitute a blend of solid and liquid lipids. The article highlights the potential role of such formulation in normalizing the in vivo fate of poorly soluble drugs. Finally, the present manuscript discusses the dominance of NLC over other lipid-based formulations and provides a perspective of how they defeat and overcome the barriers that lead to the poor bioavailability of hydrophobic drugs.

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

Abstract 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.

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

Abstract 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.

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 Parkinsons 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 Parkinsons-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 Parkinsons disease.

Nanomedicines for dental applications-scope and future perspective

Nanotechnology is directed at manipulating matter at the nanometer level and the application of the same to medicine is called nanomedicine. Over the past few years researchers have developed various nanomedicines for diagnosis, prevention as well as cure of various ailments both locally and systemically. In dentistry, drug loaded nanopharmaceuticals based on nanomaterials have been utilized extensively over the past few years to cure dental problems and facilitate attainment of a near-perfect oral hygiene. Although various drug delivery systems have already been investigated for treating periodontitis, research is currently focused on nanodelivery systems for efficient targeted delivery of drugs to the periodontal pocket. In this context a few nanodelivery systems explored include nanocomposite hydrogels, nanoparticles, nanoemulsion etc. A number of herbal and synthetic drugs examples of which include trichlosan, tetracycline, Harungana madagascariensis leaf extract, minocycline, metronidazole, chlorhexidine have been encapsulated into nanodelivery systems for treating periodontitis. A few examples of polymers investigated as matrices for the delivery of drugs to the periodontal pocket include chitosan, Poly lactic-co-glycolic acid copolymer, poly e caprolactone, polylactic acid, polypropylene, cellulose acetate propionate and ethyl vinyl acetate. In the near future also nanotechnology is expected to find its application in all the specializations of dentistry ranging from diagnosis and treatment of oral cancers to development of colloidal suspension containing millions of active analgesic micron-size dental robots resulting in anesthesia in patients. In the light of the above facts the current editorial focuses on the applications of nanotechnology based nanomedicines which cannot be undermined in the improvement of dental health and hygiene both, in the current as well as in future scenario.

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.