Breast cancer (BC) is the most common cancer among women worldwide. BC begins with an uncontrollable growth of breast cells. It is the second leading cause of disease associated with death in the United States. In India, more than 100,000 females are diagnosed annually with BC. Traditionally, several cancer treatments have been developed which include surgery, radiotherapy, chemotherapy, and hormone therapies that are not fully sufficient to treat the disease and cause more harms than benefits to patients. However, there are numbers of natural agents present but not fully explored to treat the disease. Natural agents provide an effective and efficient alternative for the chemoprevention and therapeutic treatment against BC. The natural agents can also be used in combination with other treatments such as chemotherapy and radiation to prevent from their side effects. Therefore this chapter is an attempt to highlight the potential role of natural agents in the management of BC. Further, it discusses the various nanocarriers that have been developed for these natural agents alone or in combination for increasing their activity against BC.

Objective of study was to develop and optimize nanoemulsion gel of terbinafine using Melaleuca alternifolia (tea tree) oil for synergistic antifungal activity against Candida albicans. Permeation coefficient of nanoemulsion gel and marketed cream was found to be 2.54 x 10(-3 )cm/h and 1.64 x 10(-3 )cm/h, respectively. C-skin max, AUC(0-5h), AUC(0-infinity), and penetration constant (K-p) were found to be significantly more in the skin treated with nanoemulsion gel (p < 0.0001). Confocal studies depicted deeper penetration of terbinafine from nanoemulsion gel. Moreover, FTIR and DSC analysis indicated lipid bilayer fluidization mechanism of epidermal drug deposition enhancement. Zone of inhibition for tea tree oil, nanoemulsion gel and marketed cream of terbinafine hydrochloride was found to be 10.00 +/- 1.12 mm, 43.20 +/- 1.88 mm, and 34.70 +/- 1.59 mm, respectively. These findings demonstrated that nanoemulsion gel of terbinafine containing tea tree oil could be used as promising approach to treat skin fungal infection.

Natural products are increasing used in preventing and treating various diseases. Mangiferin belongs to the xanthone family, and has potential antiangiogenic, anticancer, immunomodulatory and anti-inflammatory activity along with the antioxidant activity. It is also used in the treatment of cardiac problem, diabetes and neurodegenerative disease. Finding of various researchers proves that mangiferin has a broad spectrum therapeutic application. Motive of this review is to describe the various studies performed on mangiferin for its different pharmacological activities. It also discusses various challenges associated with mangiferin such as stability and bioavailability. Strategies and approaches to improve bioavailability of mangiferin have also been discussed. Both research and review articles were used to write the manuscript. They were collected from various search engines like Pub Med, Science Direct and Google Scholar, using keywords like mangiferin, polyphenol, bioavailability enhancement, solubility enhancement, and antioxidant. Mangiferin being a potent antioxidant is effective in the treatment of various diseases. With novel drug delivery approaches we can overcome poor solubility and bioavailability problem which eventually can result to better utilisation of mangiferin in treating a variety of diseases and make mangiferin a revolutionary drug.

In the present study resveratrol nanoemulsion gel was developed and optimized with the aim of enhancing the permeability and antioxidant activity against ultraviolet (UV)-induced oxidative skin damage. Droplet size, polydispersity index, drug permeation flux, permeability coefficient and drug deposition in skin of resveratrol-loaded nanoemulsion were found to be 65.00 ± 5.00 nm, 0.171 ± 0.082, 144.50 μg/cm2/h, 2.90 × 10–2 cm/h and 45.65 ± 4.76%, respectively, whereas drug permeation flux, permeability coefficient and drug deposition in skin from nanoemulsion gel were found to be 107.70 μg/cm2/h, 2.06 × 10–2 cm/h and 62.65 ± 4.98%, respectively. Confocal studies depicted deeper penetration of resveratrol from nanoemulsion gel. Differential scanning calorimetry and Fourier-transform infrared spectrophotometer studies confirmed that nanoemulsion gel enhanced fluidization of stratum corneum lipids and conformational disruption of lipid bilayer, thereby enhancing skin permeation of resveratrol. Histopathology study of skin revealed that resveratrol-loaded nanoemulsion gel inhibited UV-induced spongosis, edema and epidermal hyperplasia response. Levels of glutathione, superoxide dismutase, catalase and protein carbonyl in the skin of UV-irradiated rats were significantly (p < 0.01) improved in the skin of animals treated with nanoemulsion gel. Experimental results suggested that nanoemulsion gel could be explored as a promising carrier for topical delivery of resveratrol for prevention of UV-induced oxidative skin damage owing to its enhanced permeability and retention effect.

Aim: The present study was aimed at determining the antiproliferative, antioxidant, anti-inflammatory and antitumor activity of developed silymarin-nanostructured lipid carrier (NLC) gel. Materials & methods: B16 melanoma cell line and albino mice were used as ex vivo and in vivo models, respectively, to evaluate the aforementioned pharmacological activities. Results: The volume of large tumors significantly (p<0.05) reduced from 5.02 to 3.05mm(3), levels of IL-1 and TNF- were significantly (p<0.001) lower and levels of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) significantly (p<0.0001) increased in the group treated with silymarin-NLC gel. Furthermore, in skin treated with placebo and conventional gels, a basosquamous carcinoma and squamous cell carcinoma were noticed, respectively. Conclusion: Silymarin-NLC gel presented better treatment outcomes compared with silymarin-conventional gel.

Skin is the largest and easily accessible organ of the body. Increases in incidences of dermatological disorders, demand for drug targeting, and patient compliance have increased the popularity of topical drug delivery amongst the people. However, drug delivery across the skin is still a challenge for researchers because permeation of maximum drugs is hindered by the upper layer of the epidermis (stratum corneum). Several approaches like use of chemical permeation enhancers and physical methods such as sonophoresis, iontophoresis, electroporation, microneedles, etc., have been used to deliver the drugs topically. These methods of topical drug delivery have some limitations and drawbacks. Therefore new techniques based on nano drug delivery system such as ultradeformable liposomes, nanostructured lipid carriers, nanoemulsions, solid lipid nanoparticles, lipospheres, nanoparticles, and ethosomes have been exploited for enhancing epidermal and dermal drug deposition. Development of these nanosytems requires a good understanding of mechanism of drug permeation, physicochemical properties of drug and carriers, and technological advancements in methodology. Therefore, this article covers recent advances in epidermal and dermal drug deposition enhancement approaches, biopharmaceutical challenges with dermal drug delivery, issues in formulation development, and regulatory aspects of nanosystem. This review article also discusses the concern of topical drug delivery in immunization, gene delivery, and cosmeceuticals.

Duloxetine is a well-known antidepressant molecule which is used in the treatment of depression but due to poor solubility it suffers with the drawback of low oral bioavailability. The objective of present work was to formulate and characterize duloxetine loaded microemulsion to enhance the oral bioavailability. Prepared microemulsion was studied for droplet size, zeta potential, refractive index, polydispersity index (PDI), percentage transmittance, viscosity and in vitro release study. Optimized microemulsion (D1) showed spherical droplets with mean diameter of 35.40 +/- 3.11 nm, PDI of 0.170 and zeta potential values of -25.8 mV. Formulation showed good transmittance (greater than 99%), viscosity (0.205 Pa s) and refractive index (1.43 +/- 0.01). Increased duloxetine release was obtained with microemulsion in comparison to drug suspension. Behavioral tests like mobility test, tail suspension test and forced swimming test performed in depressed and treated rats with duloxetine microemulsion significantly improved the behavioral activities in comparison to duloxetine suspension. Pharmacokinetic studies showed that microemulsion exhibited 1.8 times increment in bioavailability in comparison to duloxetine suspension.

Abstract The present study was conducted for the optimization of transethosomes formulation for dermal fisetin delivery. The optimization of the formulation was carried out using “Box–Behnken design”. The independent variables were Lipoid S 100, ethanol and sodium cholate. The prepared formulations were characterized for vesicle size, entrapment efficiency and in vitro skin penetration study. The vesicles–skin interaction, confocal laser scanning microscopy and dermatokinetic studies were performed with optimized formulation. Results of the present study demonstrated that the optimized formulation presented vesicle size of 74.21 ± 2.65 nm, zeta potential of −11.0 mV, entrapment efficiency of 68.31 ± 1.48% and flux of 4.13 ± 0.17 µg/cm2/h. The TEM image of optimized formulation exhibited sealed and spherical shape vesicles. Results of thermoanalytical techniques demonstrated that the prepared transethosomes vesicles formulation had fluidized the rigid membrane of rat’s skin for smoother penetration of fisetin transethosomes. The confocal study results presented well distribution and penetration of Rhodamine B loaded transethosomes vesicles formulation up to deeper layers of the rat’s skin as compared to the Rhodamine B-hydro alcoholic solution. Present study data revealed that the developed transethosomes vesicles formulation was found to be a potentially useful drug carrier for fisetin dermal delivery.

This investigation aimed to develop nanostructured lipid carrier (NLC) gel of silymarin for epidermal tissue deposition enhancement. Binary mixture of solid lipid and liquid lipid was optimized in term of crystallinity, enthalpy of fusion and width of thermal event using DSC. NLC formulation was optimized using central composite rotatable design (CCRD). Optimized freeze dried NLC dispersion containing Sefsol® 218 (0.5% w/w), Geleol® (1.4% w/w), bile salt (1.3% w/w), Cremophor® RH40 (2.7% w/w) and mannitol (3.0% w/w) was characterized for mean particle size (PS), polydispersability index (PDI), zeta potential (ZP) and entrapment efficiency (EE). PS, PDI, ZP and EE were found to be 126.1 ± 0.4 nm, 0.33 ± 0.03, −28.8 ± 0.7 mV and 85.0 ± 2.9%, respectively. In vitro (Strat-M™ membrane) and ex vivo (rat skin) permeation studies showed close correlation (r2 = 0.98). The flux and permeability coefficient of NLC gel in ex vivo permeation studies were found to be 23.6 μg/cm2/h and 23.6 × 10−3 cm/h respectively. Dermatokinetic study showed a significant (p < 0.001) increase in CSkin max and AUC0–8h in skin treated with NLC gel as compared to skin treated with conventional gel. Confocal microscopic (CLMS) studies depicted maximum silymarin deposition in viable epidermis (30 μm). FTIR and DSC analysis indicated lipid bilayer fluidization mechanism of epidermal drug deposition enhancement. Skin irritation studies confirmed the nonirritant behavior of NLC gel to skin. These findings show that NLC gel can be used as a potential carrier for topical delivery of silymarin.

Silymarin has been approved as a safe herbal hepatoprotective drug as well as drug of choice for several hepatic disorders. However it suffers from the problem of poor oral bioavailability. In current work silymarin loaded nanoemulsions were prepared using high pressure homogenization (HPH) technique. Capryol 90, Solutol HS 15 and Transcutol HP were selected as oil phase, surfactant and co-surfactant, respectively. Quality by design was employed to optimize nanoemulsion in terms of amount of surfactant/co-surfactant mixture (S-mix), processing pressure and number of cycles. Globule size, poly-dispersity index (PDI), zeta potential, transmittance and percentage in vitro drug release of optimized formulation were found as 50.02 +/- 4.5 nm, 0.45 +/- 0.02, -31.49 mV, 100.00 +/- 2.21% and 90.00 +/- 1.83%, respectively. The everted gut sac studies showed that the nanoemulsion facilitated the improvement of the apparent permeability coefficient (P-app). P-app of silymarin in nanoemulsion and oral suspension was 1.00 x 10(-5) cm/h with flux of 0.422 mu g/cm(2)/h and 630 x 10(-6) cm/h with flux of 0.254 mu g/cm(2)/h at 2 h, respectively. Pharmacokinetic study showed significantly (p < 0.05) enhanced bioavailability of silymarin in nanoemulsion as compared to oral suspension thus nanoemulsion can be a promising oral delivery system for silymarin with enhanced oral bioavailability. (C) 2017 Elsevier B.V. All rights reserved.