Evaluation of solubility, photostability and antioxidant activity of ellagic acid cyclodextrin nanosponges fabricated by melt method and microwave-assisted synthesis.

Ellagic acid (EA) is a polyphenolic bioactive with a wide range of pharmacological activities. Regrettably, it possesses poor solubility, stability and permeability (in the gastrointestinal tract); and first-pass metabolism. Therefore, to address these challenges, the present research was aimed to encapsulate EA in cyclodextrin nanosponges (CDNS). Herein, the melt method and microwave-assisted technique have been employed for crafting CDNS. EA was loaded in CDNS via freeze-drying, followed by appropriate characterization. EA-CDNS were also assessed for encapsulation, particle size, zeta potential, and polydispersity index, which presented satisfactory results. In vitro, antioxidant activity was conducted using the DPPH (2, 2-diphenyl-1-picrylhydrazyl) assay. The solubilization efficacy of EA was analyzed in distilled water and compared with CDNS, which demonstrated ten folds augmentation for the selected batch. A remarkable improvement in the photostability of EA was also observed after its inclusion. In nutshell, the results demonstrated the superiority of the melt method in terms of solubility, entrapment, photostability, and antioxidant potential.

Insights into the mechanism of Cymbopogan martinii essential oil in topical therapy of acne vulgaris.

Aim: The present study investigated the essential oil of Cymbopogan martinii (palmarosa oil; PRO) as a potential topical therapy in acne vulgaris. Materials & methods: GC-MS profiling and biocompatibility studies of PRO were undertaken. The antimicrobial potential was assessed against Cutibacterium acnes. anti-inflammatory, antityrosinase activity and lipid peroxidation were also evaluated. Results: Geraniol was identified as the major phytoconstituent, and the oil was found to be safe for topical application. The minimum inhibitory concentration and minimum bactericidal concentration values were noted as 16 µl/ml. PRO reduced the cytokine levels of TNF-α, IL-12 and IL-8 and inhibited tyrosinase. A low concentration of the oil (up to 0.5 µl/ml) produced malondialdehyde levels equivalent to that of untreated cells. Conclusion: PRO may prove useful as a natural topical agent in the management of acne.

Lay abstract Acne vulgaris is a highly prevalent skin condition among adolescents, associated with much psychological distress in the affected individuals. The disease primarily affects the hair follicles and sebaceous glands of the face, neck, chest and back. Hormonal imbalance leads to increased production of sebum. Abnormal cellular processes cause swelling of the follicles and create an environment that is conducive to the growth of Cutibacterum acnes. The bacteria are known to initiate an immune response, rupturing the wall of hair follicles and dispersing the contents into the surrounding skin tissues. Inflammation occurs, further laying the ground for skin blemishes. Although a number of drugs are reported for the topical management of this condition, they do not address all the factors contributing to the development of acne lesions and are also reported to have several adverse effects. Therefore, the existing drugs do not offer a satisfactory solution to the problem. The growing bacterial resistance to antimicrobial drugs is another cause of concern. An agent that effectively counters the various causative factors of acne, is safe for application on human skin and is devoid of the risk of bacterial resistance, would be an ideal anti-acne agent. In this study, the essential oil derived from the plant Cymbopogan martinii (palmarosa oil) was evaluated for its potential to inhibit the growth of C. acnes, and control inflammation and blemishes associated with acne. It was also checked for its compatibility with human skin. The results were promising, advocating the essential oil as a natural and holistic solution for treating acne.

Microsponges for dermatological applications: Perspectives and challenges.

Dermatological disorders have a huge psychosocial impact, causing significant impairment of patient's life. Topical therapy plays a pivotal role in management of such disorders. Conventional topical delivery systems result in overmedication/undermedication, leading to adverse effects and reduction in therapeutic efficacy. Consequently, researchers have been striving towards the development of alternative delivery systems for dermatological applications. In the last decade, microsponges emerged as an attractive option for topical delivery. Their characteristic particle size offers enhanced benefits, making them superior to the contemporary microcarriers. The present review furnishes a comprehensive account of state of the art, important factors affecting the performance and mechanism of drug release from topically applied microsponges, along with characterization techniques. Further, a list of marketed products and their applications for common dermatological disorders has been presented. All in all, this paper is an attempt to lay a bibliographic foundation for researchers working in this field and foster further investigations in this arena.

Natural Ergot Alkaloids in Ocular Pharmacotherapy: Known Molecules for Novel Nanoparticle-Based Delivery Systems.

Several pharmacological properties are attributed to ergot alkaloids as a result of their antibacterial, antiproliferative, and antioxidant effects. Although known for their biomedical applications (e.g., for the treatment of glaucoma), most ergot alkaloids exhibit high toxicological risk and may even be lethal to humans and animals. Their pharmacological profile results from the structural similarity between lysergic acid-derived compounds and noradrenalin, dopamine, and serotonin neurotransmitters. To reduce their toxicological risk, while increasing their bioavailability, improved delivery systems were proposed. This review discusses the safety aspects of using ergot alkaloids in ocular pharmacology and proposes the development of lipid and polymeric nanoparticles for the topical administration of these drugs to enhance their therapeutic efficacy for the treatment of glaucoma.

Analytical tools and evaluation strategies for nanostructured lipid carrier-based topical delivery systems.

INTRODUCTION: The inception of nanostructured lipid carriers (NLCs) proved to be a revolutionary step toward the treatment of dermatological disorders. To uncover its true potential, it is imperative that the system be characterized and evaluated comprehensively. AREAS COVERED: The present review has been written to furnish an in-depth account of analytical tools and evaluation procedures under one roof. Besides discussing the challenges of topical delivery and benefits of NLCs, the paper elaborates on their physicochemical characterization. Further, in vitro evaluation of NLCs for dermatological benefits, followed by their evaluation in a hydrogel/cream base is covered. Lastly, disease-specific evaluation of NLC-based formulations is presented. EXPERT OPINION: The research endeavors for NLCs have largely focused on the fabrication of NLCs for different bioactives. However, scientific efforts should be aimed toward the lesser explored realm of NLCs, i.e. exploitation of analytical techniques, such as Parelectric spectroscopy, Electron Spin Resonance, and Nuclear Magnetic Resonance spectroscopy. NLCs have been proven for their potential to foster the therapeutic modalities applicable to cutaneous disorders. More attention needs to be devoted to their evaluation for disease-specific parameters. The futuristic steps must involve clinical studies, to lay the path for their commercialization.

SLN and NLC for topical, dermal, and transdermal drug delivery.

Introduction: From a biopharmaceutical standpoint, the skin is recognized as an interesting route for drug delivery. In general, small molecules are able to penetrate the stratum corneum, the outermost layer of the skin. In contrast, the delivery of larger molecules, such as peptides and proteins, remains a challenge. Nanoparticles have been exploited not only to enhance skin penetration of drugs but also to expand the range of molecules to be clinically used.Areas covered: This review focus on Solid lipid nanoparticles (SLN) and Nanostructured lipid carriers (NLC) for skin administration. We discuss the selection criteria for lipids, surfactants, and surface modifiers commonly in use in SLN/NLC, their production techniques, and the range of drugs loaded in these lipid nanoparticles for the treatment of skin disorders.Expert opinion: Depending on the lipid and surfactant composition, different nanoparticle morphologies can be generated. Both SLN and NLC are composed of lipids that resemble those of the skin and sebum, which contribute to their enhanced biocompatibility, with limited toxicological risk. SLN and NLC can be loaded with very chemically different drugs, may provide a tunable release profile, can be produced in a sterilized environment, and be scaled-up without the need for organic solvents.

Therapeutic Interventions for Countering Leishmaniasis and Chagas's Disease: From Traditional Sources to Nanotechnological Systems.

The incidence of neglected diseases in tropical countries, such as Leishmaniasis and Chagas's disease, is attributed to a set of biological and ecological factors associated with the socioeconomic context of developing countries and with a significant burden to health care systems. Both Leishmaniasis and Chagas's disease are caused by different protozoa and develop diverse symptoms, which depend on the specific species infecting man. Currently available drugs to treat these disorders have limited therapeutic outcomes, frequently due to microorganisms' drug resistance. In recent years, significant efforts have been made towards the development of innovative drug delivery systems aiming to improve bioavailability and pharmacokinetic profiles of classical drug therapy. This paper discusses the key facts of Leishmaniasis and Chagas's disease, the currently available pharmacological therapies and the new drug delivery systems for conventional drugs.

Therapeutic Potential of Citronella Essential Oil: A Review.

Mosquito-borne diseases such as malaria, filariasis, chikunguniya, yellow fever, dengue and Japanese encephalitis are the major cause of remarkable morbidity and mortality in livestock and humans worldwide. Since ancient times, aromatic plants are used for their medicinal value. Essential oils derived from these plants may be used as effective alternatives/adjuvants in pharmaceuticals, biomedical, cosmetic, food, veterinary and agriculture applications. These oils have also gained popularity and interest for prevention and treatment of various disorders. However, several reports on adverse effects including skin eruption, contact artricaria or toxic encephalopathy in children are available for synthetic repellent in the literature. Thus, natural insect repellents like essential oils have been explored recently as an alternative. One such essential oil studied widely, is citronella oil, extracted mainly from Cymbopogon nardus. This essential oil has exhibited good efficacy against mosquitoes. It is a mixture of components including citronellal, citronellol, geraniol as major constituents contributing to various activities (antimicrobial, anthelmintic, antioxidant, anticonvulsant antitrypanosomal and wound healing), besides mosquito repellent action. Citronella essential oil is registered in US EPA (Environmental protection agency) as insect repellent due to its high efficacy, low toxicity and customer satisfaction. However, poor stability in the presence of air and high temperature limits its practical applications. Since specific knowledge on properties and chemical composition of oil is fundamental for its effective application, the present review compiles and discusses biological properties of citronella oil. It also sheds light on various formulations and applications of this essential oil.

Nanotherapeutics: An insight into healthcare and multi-dimensional applications in medical sector of the modern world.

In recent years nanotechnology has revolutionized the healthcare strategies and envisioned to have a tremendous impact to offer better health facilities. In this context, medical nanotechnology involves design, fabrication, regulation, and application of therapeutic drugs and devices having a size in nano-range (1-100 nm). Owing to the revolutionary implications in drug delivery and gene therapy, nanotherapeutics has gained increasing research interest in the current medical sector of the modern world. The areas which anticipate benefits from nano-based drug delivery systems are cancer, diabetes, infectious diseases, neurodegenerative diseases, blood disorders and orthopedic problems. The development of nanotherapeutics with multi-functionalities has considerable potential to fill the lacunae existing in the present therapeutic domain. Nanomedicines in the field of cancer management have enhanced permeability and retention of drugs thereby effectively targeting the affected tissues. Polymeric conjugates of asparaginase, polymeric micelles of paclitaxel have been recmended for various types of cancer treatment .The advancement of nano therapeutics and diagnostics can provide the improved effectiveness of the drug with less or no toxicity concerns. Similarly, diagnostic imaging is having potential future applications with newer imaging elements at nano level. The newly emerging field of nanorobotics can provide new directions in the field of healthcare. In this article, an attempt has been made to highlight the novel nanotherapeutic potentialities of polymeric nanoparticles, nanoemulsion, solid lipid nanoparticle, nanostructured lipid carriers, dendrimers, nanocapsules and nanosponges based approaches. The useful applications of these nano-medicines in the field of cancer, nutrition, and health have been discussed in details. Regulatory and safety concerns along with the commercial status of nanosystems have also been presented. In summary, a successful translation of emerging nanotherapeutics into commercial products may lead to an expansion of biomedical science. Towards the end of the review, future perspectives of this important field have been introduced briefly.

Novel Carriers for Coenzyme Q10 Delivery.

BACKGROUND: Coenzyme Q10, a natural yellow benzoquinone, is a vitamin-like substance commonly found in blood and inner mitochondrial and cellular membranes. It is a natural antioxidant principle which plays an essential role in maintaining several biochemical pathways of body. It has exhibited many pharmacological activities in chronic heart failure, cardiofaciocutaneous syndrome, diabetes mellitus, carcinomas, autoimmune disease, cataract, asthma, periodontal disease and thyroid disorders. Moreover, it has demonstrated efficacy as nutritional supplement, in addition to its relevance in cosmetics. OBJECTIVE: Coenzyme Q10 is a potent molecule but its high molecular weight and low aqueous solubility hamper its use as a therapeutic agent. Therefore, various novel drug delivery systems have been explored and developed to overcome these limitations in literature. Hence, objective of this review is to summarize the recent works on design and development of novel drug delivery systems for CoQ10, which include liposomes, polymeric nanoparticles, polymeric micelles, solid lipid nanoparticles, nanostructured lipid carriers, self-emulsifying drug delivery systems, nanoemulsions, solid and aqueous dispersions. Further, an account of pharmaceutical studies has also been given. RESULTS & CONCLUSION: The reported studies indicate the promise of nanotechnology in enhancing the therapeutic value of CoQ10, promoting its usage as first line therapeutic agent, thus, revolutionizing its role in current medical therapy. The application of CoQ10 in pharmaceutical industry has grown tremendously in the past decade, due to its versatile nature. The successful application of this molecule in medicine, cosmetics and nutraceuticals points the way for its future development.

Transdermal innovations in diabetes management.

Diabetes mellitus, an endocrine disorder affecting glucose metabolism, has been crippling mankind for the past two centuries. Despite the advancements in the understanding pertaining to its pathogenesis and treatment, the currently available therapeutic options are far from satisfactory. The growing diabetic population increases the gravity of the situation. The shortcomings of the conventional drug delivery systems necessitate the need to delve into other routes. On account of its merits over other routes, the transdermal approach has drawn the interest of the researchers around the world. The transdermal drug delivery systems are aimed to achieve therapeutic concentrations of the drug through skin. These systems are designed so that the drug can be delivered at a pre-determined and controlled rate. This makes it particularly conducive to treat chronic disorders like diabetes. Correspondingly, the adverse effects and inconvenience concomitant with oral and parentral route are circumvented. This article attempts to outline the development of transdermal drug delivery systems to optimize diabetes pharmacotherapy. It not only covers the transdermal approaches adopted to fine-tune insulin delivery, but also, discusses various transdermal drug delivery systems fabricated to improve the therapeutic performance of oral hypoglycaemic agents. Such formulations include the advanced drug delivery systems, namely, transferosomal gels, microemulsions, self-dissolving micropiles, nanoparticles, insulin pumps, biphasic lipid systems, calcium carbonate nanoparticles, lecithin nanoparticles; physical techniques such as iontophoresis and microneedles and, drugs formulated as transdermal patches. In addition to this, the authors have also shed light on the future prospects and patented and commercial formulations of antidiabetic agents.

Formulation and characterization of benzoyl peroxide gellified emulsions.

The present investigation was carried out with the objective of formulating a gellified emulsion of benzoyl peroxide, an anti-acne agent. The formulations were prepared using four different vegetable oils, viz. almond oil, jojoba oil, sesame oil, and wheat germ oil, owing to their emollient properties. The idea was to overcome the skin irritation and dryness caused by benzoyl peroxide, making the formulation more tolerable. The gellified emulsions were characterized for their homogeneity, rheology, spreadability, drug content, and stability. In vitro permeation studies were performed to check the drug permeation through rat skin. The formulations were evaluated for their antimicrobial activity, as well as their acute skin irritation potential. The results were compared with those obtained for the marketed formulation. Later, the histopathological examination of the skin treated with various formulations was carried out. Formulation F3 was found to have caused a very mild dysplastic change to the epidermis. On the other hand, the marketed formulation led to the greatest dysplastic change. Hence, it was concluded that formulation F3, containing sesame oil (6%w/w), was the optimized formulation. It exhibited the maximum drug release and anti-microbial activity, in addition to the least skin irritation potential.