Development and Evaluation of Dutasteride Nanoemulgel for the Topical Delivery against Androgenic Alopecia.

BACKGROUND: Dutasteride is approximately three times more potent than finasteride in treating alopecia. For reducing systemic exposure to dihydrotestosterone (DHT), researchers have shown special interest in developing topical formulations for treating androgenic alopecia. Dutasteride emulsification may lead to good skin penetration and improved availability in different lipophilic skin environments. OBJECTIVES: This study aimed to encapsulate the drug into the lipidic carrier system for better local availability in the scalp skin, develop and evaluate nanoemulgel of dutasteride to ensure efficient topical administration, and perform the in-vivo activity of the developed gel for improved efficacy against alopecia. METHODS: Dutasteride-loaded nanoemulsion was prepared by a high-speed homogenizer, followed by thickening of the dispersion using Carbopol 934. Skin permeation and accumulation were investigated in the excised skin of male Swiss albino mice. The nanoemulgel was characterized based on pH, stress stability, viscosity, and hardness. RESULTS: The optimized dutasteride-loaded nanoemulsion had a size of 252.33 ± 8.59 nm, PDI of 0.205 ± 0.60, and drug content of 98.65 ± 1.78%. Stress stability was performed was well observed in nanoemulsion formulation. Nanoemulgel evaluation results were as follows: pH 5-6 was desirable for topical application, hardness was 43 gm, and spreadability was 79 gm with in vitro release of nanoemulgel at 91.98% and permeation study at 13.67%. CONCLUSION: The in vivo studies demonstrated the growth of newer hair follicles and increased hair diameter and length in dutasteride-loaded nanoemulgel-treated alopecia animals compared to the marketed sample and testosterone-treated group. Provided with the same and long-term storage stability, the developed formulation is supposed to offer a good option for the topical administration of dutasteride in treating androgenic alopecia.

An Update on Pharmacological and Phytochemical Aspects of Costus pictus D. Don - A Promising Anti-diabetic Plant.

BACKGROUND: The genus Costus is the largest genus in the family Costaceae and encompasses about 150 known species. Among these, Costus pictus D. Don (Synonym: Costus mexicanus) is a traditional medicinal herb used to treat diabetes and other ailments. Currently, available treatment options in modern medicine have several adverse effects. Herbal medicines are gaining importance as they are cost-effective and display improved therapeutic effects with fewer side effects. Scientists have been seeking therapeutic compounds in plants, and various in vitro and in vivo studies report Costus pictus D. Don as a potential source in treating various diseases. Phytochemicals with various pharmacological properties of Costus pictus D. Don, viz. anticancer, anti-oxidant, diuretic, analgesic, and anti-microbial have been worked out and reported in the literature. OBJECTIVE: The aim of the review is to categorize and summarize the available information on phytochemicals and pharmacological properties of Costus pictus D. Don and suggest outlooks for future research. METHODS: This review combined scientific data regarding the use of Costus pictus D. Don plant for the management of diabetes and other ailments. A systematic search was performed on Costus pictus plant with anti-diabetic, anti-cancer, anti-microbial, anti-oxidant, and other pharmacological properties using several search engines such as Google Scholar, PubMed, Science Direct, SciFinder, other online journals and books for detailed analysis. RESULTS: Research data compilation and critical review of the information would be beneficial for further exploration of its pharmacological and phytochemical aspects and, consequently, new drug development. Bioactivity-guided fractionation, isolation, and purification of new chemical entities from the plant as well as pharmacological evaluation of the same will lead to the search for safe and effective novel drugs for better healthcare. CONCLUSION: This review critically summarizes the reports on natural compounds, and different extract of Costus pictus D. Don with their potent anti-diabetic activity along with other pharmacological activity. Since this review has been presented in a very interactive manner showing the geographical region of availability, parts of plant used, mechanism of action and phytoconstituents in different extracts of Costus pictus responsible for particular action, it will be of great importance to the interested readers to focus on the development of the new drug leads for the treatment of diseases.

PVP-microneedle array for drug delivery: mechanical insight, biodegradation, and recent advances.

Microneedle arrays are micron-sized needles usually attached to a supporting base or patch facilitated drug delivery for systemic effects. Polyvinylpyrrolidone (PVP) is a lactam polymer containing an internal amide linkage. Because of its versatility and biocompatibility, it has been widely utilized to treat several skin, bone and eye problems. Due to its specific and unique properties, the researchers realize its utility as a polymer of tremendous potential. PVP-based dissolvable microneedles have widely been utilized as a carrier for delivering DNAs, proteins, vitamins, and several biological macromolecules transdermally. However, it does not get biodegraded into the body. Therefore, the presence of its fragments in the body post-treatment needs proper justification. The adequate justification for the fate of the fragment's end products in the body will allow even better utilization of PVP. This review analyses and illustrates various experimental findings to highlight the most recent advancements and applications of PVP microneedles in drug delivery systems and cosmetology and the potential for PVP microneedles in treating dermal and systemic disorders. This review presents the expected mode of PVP biodegradation in aqueous and soil environments as a waste material, its inertness, biocompatibility, and the importance of PVP as a fabricating material, pharmaceutical uses, and non-toxic profile.

Cliv-92-Loaded Glycyrrhetinic Acid-Modified Chitosan Nanoparticles for Enhanced Hepatoprotection-Preparation, Characterization, and In Vivo Evaluation.

Cliv-92 is a mixture of three structurally similar coumarinolignoids and a proven hepatoprotective agent. Low aqueous solubility and poor bioavailability are notable hindrances for its further use. Therefore, glycyrrhetinic acid-linked chitosan nanoparticles loaded with Cliv-92 were prepared for active targeting to the liver. The nanoparticles were prepared by the ionic gelation method to avoid the use of toxic solvents/rigorous agitation. The method of preparation was optimized using a central composite design with independent variables, namely polymer: drug ratio (3:1, w/w), crosslinker concentration (0.5%), and stirring speed (750 rpm). The optimized nanoparticles had a mean particle size of 185.17 nm, a polydispersity index of 0.41, a zeta potential of 30.93 mV, and a drug loading of 16.30%. The prepared formulation showed sustained release of approximately 63% of loaded Cliv-92 over 72 h. The nanoparticles were freeze-dried for long-term storage and further characterized. The formulation was found to be biocompatible for parenteral delivery. In vivo imaging study showed that optimized nanoparticles were preferentially accumulated in the liver and successfully targeting the liver. The present study successfully demonstrated the improved pharmacokinetic properties (≈12% relative bioavailability) and efficacy profile (evidenced by in vivo and histopathological studies) of fabricated Cliv-92 nanoparticles.

A study of thyroid profile in patients suffering from the first episode of mania: A cross-sectional study.

BACKGROUND: Thyroid function is commonly considered in the assessment of mood disorders. Reports of thyroid dysregulation in patients with mania are associated with several confounding factors. To eliminate confounding factors, studies of first-episode mania are desirable. This study tried to find out any relationship between thyroid disorders and mania. AIM: The aim of this study is to assess and compare the thyroid profile between first-episode mania and healthy controls and to ascertain the correlation between severity and duration of the manic episode with FT3, FT4, and thyroid-stimulating hormone (TSH) levels. MATERIALS AND METHODS: This was a cross-sectional study conducted in the psychiatry department of a tertiary care hospital. Forty consecutive drug-naïve patients with first-episode mania, diagnosed according to the International Classification of Disease-10 (study group), were matched with 40 healthy controls (control group). Both the groups were compared on the basis of thyroid profile and thyroid levels were correlated with duration and severity of illness in the study group. RESULTS: Nearly 7.5% of cases in the study group had hyperthyroidism, whereas 5% had subclinical hyperthyroidism. In contrast, normal controls showed 5% and 10% prevalence of hypothyroidism and subclinical hypothyroidism, respectively. A statistically significant lower level of TSH was observed in the study group (P < 0.001), whereas the mean serum levels of FT3 and FT4 were higher in the study group, but the difference was statistically nonsignificant. No significant correlation of thyroid hormones level with duration and severity of illness was noted. CONCLUSION: Our findings highlight a higher prevalence of hyperthyroidism in patients with mania and suggest the role of thyroid hormones in mania.

Anti-psoriatic effect of Lavandula angustifolia essential oil and its major components linalool and linalyl acetate.

ETHNO-PHARMACOLOGICAL RELEVANCE: Lavender oil (LO) is an aromatic/essential oil extracted from Lavandula angustifolia and traditionally used as an aromatherapy massage oil due to its anti-inflammatory and wound healing property and also for providing the relief in other skin conditions such as psoriasis, dermatitis and eczema. However, LO has not been evaluated scientifically for psoriasis like skin inflammation. AIM OF THE STUDY: This study was aimed to investigate the LO and its major components linalool (L) and linalyl acetate (LA) against psoriasis like skin inflammation. MATERIALS AND METHODS: Anti-psoriatic activity was done using Imiquimod (IMQ) induced psoriasis like skin inflammation in BALB/c mice. Assessment of anti-psoriatic effect of LO, L and LA was done on the basis of change in ear thickness, psoriasis area severity index (PASI) scoring at alternative day, CosCam scoring using skin analyzer equipped with SkinSys software, biochemical, immunohistochemical and histological investigations. Level of effectiveness against psoriasis was investigated by percent reduction in PASI scores, CosCam scores and level of Th-1 and Th-17 cell expressing cytokines, as compared to the diseased mice. RESULTS: Topical application of LO 10% showed 73.67% recovery in PASI and 87% in Th-17 cell-specific cytokines towards normal as compared to disease group. L and LA were identified as the major components of LO and favoured ligands for selected psoriasis targets. At 2% topical dose, L and LA showed 64% and 47.61% recovery in PASI scores, respectively. Both, L and LA showed significant recovery in Th-1 specific TNF-α and IL-1ß however, only L showed significant recovery of Th-17 cytokines (IL-17 and IL-22). In contrast to LA (which restored granulosis), L restored epidermal hyperplasia and parakeratosis toward the normal condition. On the other hand, L also reduced the expression of NF-κß, ccr6 and IL-17, while LA reduced the expression of NF-κß only. At 10% topical dose, LO was observed to be slight irritant while at 2% topical dose, L and LA were found non-irritant to the skin. CONCLUSION: This study proves the effectiveness of LO and its major phytoconstituents linalool and linalyl acetate against IMQ induced psoriasis like skin inflammation and provides the scientific evidence for topical use of lavender oil.

Nanoemulsion as pharmaceutical carrier for dermal and transdermal drug delivery: Formulation development, stability issues, basic considerations and applications.

The use of nanoemulsion in augmenting dermal and transdermal effectiveness of drugs has now well established. The development of nanoemulsion based semisolid dosage forms is an active area of present research. However, thickening or liquid-to-semisolid conversion of the nanoemulsions provides opportunities to the formulation scientist to explore novel means of solving instability issues during transformation. Extending knowledge about the explicit role of nature/magnitude of zeta potential, types of emulsifiers and selection of appropriate semisolid bases could place these versatile carriers from laboratory to industrial scale. This article reviews the progressive advancement in the delivery of medicament via nanoemulsion with special reference to the dermal and transdermal administration. It is attempted to explore the most suitable semi solid dosage form for the particular type of nanoemulsion (o/w, w/o and others) and effect of particle size and zeta potential on the delivery of drugs through dermal or transdermal route. Finally, this review also highlights the basic principles and fundamental considerations of nanoemulsion manufacture, application of nanoemulsion based semisolid dosage forms in the dermal/transdermal administration and basic considerations during the nanoemulsion absorption into and through skin.

Wound Healing Activity of Azadirachta indica A. Juss Stem Bark in Mice.

BACKGROUND: The paste of stem bark of Azadirachta indica (AI) has been traditionally used on wound and scar for rapid healing in Bundelkhand region of India. OBJECTIVE: In the present investigation, wound healing potential of different extracts of stem bark of AI was explored in mice model. MATERIALS AND METHODS: To study the wound healing properties in small animal model, the excision and incision wound models were used and water, ethanol-water (1:1, v/v) and ethanol extracts were applied topically (15% w/w in ointment base). In the excision wound model, wound contraction, hydroxyproline content, DNA content, protein content, and nitric oxide levels were estimated after 14 days of topical treatment along with histopathological examinations. In the incision wound model, wound breaking strength was determined after 10 days of topical application of different extracts of AI. RESULTS: The animals treated with water extract of AI exhibited significant increment in rate of wound contraction (93.39%, P < 0.01), hydroxyproline content (13.31 ± 6.65 mg/g of dry tissue, P < 0.001), DNA content (20.99 ± 0.68 µg/100 mg of tissue, P < 0.01), protein content (100.53 ± 7.88 mg/g of wet tissue, P < 0.01) and nitric oxide level (3.05 ± 0.03 mMol/g of tissue, P < 0.001) as well as in wound breaking strength (289.40 ± 29.45 g, P < 0.01) when compared with vehicle control group which was also supported by histopathological studies. CONCLUSION: The water extract of stem bark of AI possesses significant wound healing property, validating its traditional use.

Polysaccharide Encrusted Multilayered Nano-Colloidal System of Andrographolide for Improved Hepatoprotection.

Andrographolide (AP), a phytoconstituent of Andrographis paniculata is reported as a potent hepatoprotective agent. However, utility of this molecule is restricted due to its low aqueous solubility, gastric instability and hence low bioavailability. It was aimed to formulate and characterize AP-loaded, natural biopolymer stabilized, multilayered nano-hydrocolloid delivery system. Nanoemulsion (NE) was formulated using layer-by-layer (LbL) technology via electrostatic deposition of chitosan over alginate encrusted o/w NE by ultra-sonication. Improved transparency and stability of NE were observed with increasing sonication time. Best stability was obtained after 20 min sonication and particle size of the multilayered NE was measured in the range of 90.8-167.8 nm. Transmission electron microscopy confirmed the progressive layering of nanosized NE. Higher magnitude of zeta potential (i.e., 22.9 to 31.01 mV) confirmed higher stability and coating of alginate layer over NE surface for the period of 3 months. NE showed strategic release pattern when assessed in vitro in various simulated biological fluids of GIT in timed pattern. Multilayered NE showed significant modulation in liver function test (ALT, ALP, AST, TBIL, DBIL, and liver glycogen) and serum cytokines (TNF-α, IL-6, IL-10, and IL-ß) when assessed in vivo in galactosamine-lipopolysaccharide intoxicated mice. In conclusion, the andrographolide engrained multi-layered NE enhanced the solubility, stability and henceforth assured the increased availability in simulated biological fluids. The in vivo study exhibited the significantly improved hepatoprotection by andrographolide when delivered in stable multi-layered NE carrier systems.

Encapsulation of Mentha Oil in Chitosan Polymer Matrix Alleviates Skin Irritation.

Mentha spicata L. var. viridis oil (MVO) is a potent antifungal agent, but its application in the topical treatment is limited due to its irritancy and volatility. It was aimed to develop more efficient, chitosan-incrusted MVO microspheres with reduced volatility and lesser irritancy and to dispense it in the form of ointment. Simple coacervation technique was employed to microencapsulate MVO in chitosan matrix. Morphological properties and polymer cross-linking were characterized by scanning electron microscopy and differential scanning calorimetry, respectively. Optimization was carried out on the basis of entrapment efficiency (EE) using response surface methodology. Well-designed microspheres having smooth surface and spherical shape were observed. EE (81.20%) of optimum batch (R21) was found at 1.62% w/v of cross-linker, 5.4:5 of MVO to chitosan ratio and at 1000 rpm. R21 showed 69.38 ± 1.29% in vitro MVO release in 12 h and 96.92% retention of MVO in microspheres even after 8 week. Ointments of PEG 4000 and PEG 400 comprising MVO (F1) and R21 (F2) were developed separately. F2 showed comparatively broader zone of growth inhibition (13.33 ± 1.76-18.67 ± 0.88 mm) and less irritancy (PII 0.5833, irritation barely perceptible) than that of F1. F2 was able to avoid the direct contact of mild irritant MVO with the skin and to reduce its rapid volatility. Controlled release of MVO helped in lengthening the duration of availability of MVO in agar media and hence improved its therapeutic efficacy. In conclusion, a stable and non-irritant formulation with improved therapeutic potential was developed.

An assessment of wound healing potential of Argyreia speciosa leaves.

In North India, poultice of young unfolded leaves of Argyreia speciosa Linn. (Convolvulaceae) is used for healing wounds. In order to find scientific evidence for the traditional utilization of leaves of A. speciosa in wound healing, this investigation was carried out. A linear incision wound of about 3 cm in length and 2 mm in depth and circular excision wound of 177 mm(2) full thickness were made on the dorsal region of separate groups (n = 5) of anesthetized Swiss albino mice. A simple ointment, developed by including ethanol, ethanol-water, and water extracts (10% each, separately) of A. speciosa, was applied topically to mice once daily for 14 days after wounding. To evaluate the effect of each extract, wound contraction, epithelization period, wound breaking strength, and hydroxyproline content were determined. The water extract of A. speciosa showed accelerated wound healing activity as evidenced by fast wound contraction (96.30 ± 0.52%; P < 0.01), rapid epithelization period (11.40 ± 0.60 days; P < 0.001), greater wound breaking strength (376.56 ± 21.16 g; P < 0.001), and higher hydroxyproline content (16.49 ± 1.12 mg/g; P < 0.05) of granulation tissue. The present report supports the traditional use of Argyreia speciosa leaves for wound healing and signify its relevant therapeutic potential.

In vivo anti-diabetic activity of derivatives of isoliquiritigenin and liquiritigenin.

Isoliquiritigenin (ISL), a chalcone and liquiritigenin (LTG), a flavonoid found in licorice roots and several other plants. ISL displays antioxidant, anti-inflammatory, antitumor and hepatoprotective activities whereas LTG is an estrogenic compound, acts as an agonist selective for the ß-subtype of the oestrogen receptor. Both the phenolics were isolated from the rhizomes of Glycyrrhiza glabra. Five derivatives from ISL and four derivatives from LTG were synthesized. All the compounds were established by extensive spectroscopic analyses and screened through oral glucose tolerance test to gain preliminary information regarding the antihyperglycemic effect in normal Swiss albino male mice. ISL (1), ISL derivatives 3, 4, 5, 7 and LTG derivatives 9 and 10 showed significant blood glucose lowering effect. The structure-activity relationship indicated that the presence of ether and ester groups in ISL and LTG analogues are important for exhibiting the activity. Compounds 1, 4 and 10 were selected for in vivo antidiabetic activity and found to be potential candidates for treatment of diabetes. It is the first report on antidiabetic activity of ISL derivative 4 and LTG derivative 10.

Efficient hepatic delivery of drugs: novel strategies and their significance.

Liver is a vital organ responsible for plethora of functions including detoxification, protein synthesis, and the production of biochemicals necessary for the sustenance of life. Therefore, patients with chronic liver diseases such as viral hepatitis, liver cirrhosis, and hepatocellular carcinoma need immediate attention to sustain life and as a result are often exposed to the prolonged treatment with drugs/herbal medications. Lack of site-specific delivery of these medications to the hepatocytes/nonparenchymal cells and adverse effects associated with their off-target interactions limit their continuous use. This calls for the development and fabrication of targeted delivery systems which can deliver the drug payload at the desired site of action for defined period of time. The primary aim of drug targeting is to manipulate the whole body distribution of drugs, that is, to prevent distribution to non-target cells and concomitantly increase the drug concentration at the targeted site. Carrier molecules are designed for their selective cellular uptake, taking advantage of specific receptors or binding sites present on the surface membrane of the target cell. In this review, various aspects of liver targeting of drug molecules and herbal medications have been discussed which elucidate the importance of delivering the drugs/herbal medications at their desired site of action.

Enrichment, development, and assessment of Indian basil oil based antiseptic cream formulation utilizing hydrophilic-lipophilic balance approach.

The present work was aimed to develop an antiseptic cream formulation of Indian basil oil utilizing hydrophilic-lipophilic balance approach. In order to determine the required-hydrophilic lipophilic balance (rHLB) of basil oil, emulsions of basil oil were prepared by phase inversion temperature technique using water, Tween 80, and Span 80. Formulated emulsions were assessed for creaming (BE9; 9.8, BE10; 10.2), droplet size (BE18; 3.22 ± 0.09 µ m), and turbidity (BE18; 86.12 ± 2.1%). To ensure correctness of the applied methodology, rHLB of light liquid paraffin was also determined. After rHLB determination, basil oil creams were prepared with two different combinations of surfactants, namely, GMS : Tween 80 (1 : 3.45) and SLS : GMS (1 : 3.68), and evaluated for in vitro antimicrobial activity, skin irritation test, viscosity and consistency. The rHLB of basil oil and light liquid paraffin were found to be 13.36 ± 0.36 and 11.5 ± 0.35, respectively. Viscosity, and consistency parameters of cream was found to be consistent over 90 days. Cream formulations showed net zone of growth inhibition in the range of 5.0-11.3 mm against bacteria and 4.3-7.6 mm against fungi. Primary irritation index was found to be between 0.38 and1.05. Conclusively stable, consistent, non-irritant, enriched antiseptic basil oil cream formulations were developed utilizing HLB approach.

Development and characterization of cellulose-polymethacrylate mucoadhesive film for buccal delivery of carvedilol.

The aim of the present work was to develop and characterize mucoadhesive film of cellulose (methyl cellulose and hydroxy propyl methyl cellulose) and polymethacrylate (Eudragit RSPO) polymers for buccal delivery of carvedilol. Drug and polymers were found to be compatible as revealed by FTIR and DSC analysis. Mucoadhesive films were prepared by solvent casting technique. Swelling studies up to 4h did not show erosion of film, which was further confirmed by SEM analysis. New, simple and precise instrumental methods were established for the evaluation of mucoadhesive strength (33.8 ± 0.37-38.4 ± 0.24 g) and film strength (331.2 ± 0.73-369.0 ± 1.00 g) of developed films. Mucoadhesive film F5 showed 88 ± 1.15% in vitro drug release and 80 ± 2.30% ex vivo drug permeation through goat buccal mucosa in 12h. Drug release and permeation followed Higuchi's model and mechanism was found to be Fickian type diffusion controlled.