Priyam Sinha

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.

Development of cellulosic polymer based gel of novel ternary mixture of miconazole nitrate for buccal delivery.

Aim of the present investigation was to develop cellulosic polymer based mucoadhesive antifungal gel comprising novel ternary mixture of miconazole nitrate (MN) for buccal delivery. Crosslinking of gel was made by adjusting pH with triethanolamine (TEA) and gel formulation was optimized on the basis of flux of MN (0.562-1.751 mg/cm(2)/h) calculated from ex vivo permeation study. Based on statistically validated polynomial equation and plotted response surfaces, B17 was found to be the optimum batch. Texture profile in terms of adhesiveness (3.24 ± 0.012 g), firmness (10.83 ± 0.067 g), spreadability (3.63 ± 0.033 mJ) and extrudability (35.6 ± 0.1 mJ) of B17 was evaluated using a novel instrumental approach. The texture parameters were found to be consistent over 90 days. Ternary mixture containing gel showed broader zone of growth inhibition (32.67-47.33 mm) in comparison to marketed formulation containing pure MN (17.50-40.33 mm) against selected strains of fungi. In conclusion, consistent and effective mucoadhesive antifungal gel of MN with extended residence time in oral mucosa was developed.

Determination of required hydrophilic–lipophilic balance of citronella oil and development of stable cream formulation

Context: Citronella oil is reported to have excellent mosquito-repellent activity. To develop a stable cream formulation (emulsion), its hydrophilic–lipophilic balance (HLB) value is important. Objective: To determine required hydrophilic–lipophilic balance (rHLB) value of citronella oil and to develop stable cream formulation. Materials and Methods: Emulsions of citronella oil were prepared by phase inversion temperature technique using water, Tween 80 and Span 80. A first series of 11 emulsions with HLB values ranging from 5.0 to 15.0 and a second series of eight emulsions with smaller interval in HLB values from 11.0 to 13.8 were prepared. Emulsions were evaluated for creaming index, droplet size and turbidity to determine rHLB. Utilizing determined rHLB, citronella oil cream was formulated and evaluated for different texture parameters. rHLB of light liquid paraffin was also determined for validation of methodology. Results: rHLB of light liquid paraffin and citronella oil was determined to be 11.80 and 12.60, respectively. Stable citronella oil cream was developed with 10% emulsifier blend. Texture parameters were found to be consistent over the entire storage period. Discussion: Creaming index, droplet diameter, percent increase in droplet diameter and turbidity are the established parameters to determine rHLB and to develop stable emulsion. Emulsions with optimum emulsifier concentration resulted in less percentage creaming index, smallest droplet, less percentage increase in droplet diameter and highest turbidity. Texture properties evaluation ensures the stability of the developed cream. Conclusion: rHLB value of citronella oil was found 12.6 and a stable cream was formulated utilizing determined rHLB.

New Perspectives on Antiacne Plant Drugs: Contribution to Modern Therapeutics

Acne is a common but serious skin disease, which affects approximately 80% adolescents and young adults in 11–30 age group. 42.5% of men and 50.9% of women continue to suffer from this disease into their twenties. Bacterial resistance is now at the alarming stage due to the irrational use of antibiotics. Hence, search for new lead molecule/bioactive and rational delivery of the existing drug (for better therapeutic effect) to the site of action is the need of the hour. Plants and plant-derived products have been an integral part of health care system since time immemorial. Therefore, plants that are currently used for the treatment of acne and those with a high potential are summarized in the present review. Most active plant extracts, namely, P. granatum, M. alba, A. anomala, and M. aquifolium exhibit minimum inhibitory concentration (MIC) in the range of 4–50 µg/mL against P. acnes, while aromatic oils of C. obovoides, C. natsudaidai, C. japonica, and C. nardus possess MICs 0.005–0.6 μL/mL and phytomolecules such as rhodomyrtone, pulsaquinone, hydropulsaquinone, honokiol, magnolol, xanthohumol lupulones, chebulagic acid and rhinacanthin-C show MIC in the range of 0.5–12.5 μg/mL. Novel drug delivery strategies of important plant leads in the treatment of acne have also been discussed.

A Novel Approach for Development and Characterization of Effective Mosquito Repellent Cream Formulation Containing Citronella Oil

Citronella essential oil (CEO) has been reported as an excellent mosquito repellent; however, mild irritancy and rapid volatility limit its topical application. It was aimed to develop a nonirritant, stable, and consistent cream of CEO with improved residence time on skin using an industrial approach. Phase inversion temperature technique was employed to prepare the cream. It was optimized and characterized based on sensorial evaluation, emulsification, and consistency in terms of softness, greasiness, stickiness, and pH. The optimum batch (B5) was evaluated for viscosity (90249.67 ± 139.95 cP), texture profile with respect to firmness (38.67 ± 0.88 g), spreadability (70.33 ± 0.88 mJ), and extrudability (639.67 ± 8.09 ± 0.1 mJ) using texture analyzer along with two most popular marketed products selected as reference standard. Subsequently, B5 was found to be stable for more than 90 days and showed enhanced duration of mosquito repellency as compared to CEO. HS-GC ensured the intactness of CEO in B5. Investigated primary irritation index (PII 0.45) positioned B5 into the category of irritation barely perceptible. The pronounced texture profile and stability of B5 with extended residence time and less PII revealed its potential application in industry and offered a promising alternative to the marketed products of synthetic origin.

Phyto–vesicles: conduit between conventional and novel drug delivery system

Abstract Objective To discuss the preparation, characterization, targeting and formulation aspect of phospholipids based drug delivery system i.e. Phyto–vesicles. Methods The methods of phyto–vesicles preparation on R & D scale and different analytical techniques to characterize them have been discussed. Result Phyto–vesicles are the advanced form of herbal drug delivery systems as its structure includes water soluble head and two fat soluble tails which act as an effective emulsifier. Conclusion It is concluded that phytovesicular delivery system has improved pharmacokinetic and pharmacodynamic parameter as compared to conventional system Therefore, phyto–vesicles are called as conduit between conventional and novel drug delivery system.

Colloidal Vesicular System of Inositol Hexaphosphate to Counteract DMBA Induced Dysregulation of Markers Pertaining to Cellular Proliferation/Differentiation and Inflammation of Epidermal Layer in Mouse Model

Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells. The shortcoming is its quick absorption on oral/topical administration. Niosomes are flexible carriers for topical drug delivery. The central venture of current research was to optimize and characterize niosomal delivery system of IP6 for treatment of skin cancer. Thin film hydration method was utilized to prepare IP6 niosomes, and these were dispersed as a suspension in a suitable base. Developed formulations were analyzed for various physicochemical and pharmacological parameters such as particle size, encapsulation efficiency, morphology, drug release, texture analysis, irritability, cell line studies, Western blotting, RT-PCR, and histopathology. IP6 niosomal suspension and IP6 in acetone displayed IC50 value at the concentration of 0.96 mM (0.63 mg/mL) and 1.39 mM (0.92 mg/mL), respectively. IP6 niosomal suspension showed significantly higher (p < 0.05) activity and showed cytotoxic effect in SK-MEL-2 cancer cell line. Crucial events of cellular proliferation and differentiation, like expression of ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cycloxygenase-2 (COX-2) and Cyclin D1 were initiated from the fourth hour through application of 7,12-dimethylbenzanthracene (DMBA) on albino mice. The DMBA altered expression of aforesaid enzymes was significantly (P < 0.001) prevented by concomitant application of niosomal formulations. Results of cell line study, Western blotting, RT-PCR, and histopathology suggested that IP6 niosomal suspension could constitute a promising approach for prevention of cellular proliferation as well as DMBA induced dysregulation of cellular proliferation/differentiation and inflammation.

Development, optimization, and characterization of a novel tea tree oil nanogel using response surface methodology

Abstract Purpose: To develop and optimize nanoemulsion (NE)-based emulgel (EG) formulation as a potential vehicle for topical delivery of tea tree oil (TTO). Methodology: Central composite design was adopted for optimizing the processing conditions for NE preparation by high energy emulsification method viz. surfactant concentration, co-surfactant concentration, and stirring speed. The optimized NE was developed into emulgel (EG) using pH sensitive polymer Carbopol 940 and triethanolamine as alkalizer. The prepared EG was evaluated for its pH, viscosity, and texture parameters, ex vivo permeation at 37 °C and stability. Antimicrobial evaluation of EG in comparison to conventional gel and pure TTO was also carried out against selected microbial strains. Results and discussion: Optimized NE had particle size and zeta potential of 16.23 ± 0.411 nm and 36.11 ± 1.234 mV, respectively. TEM analysis revealed the spherical shape of droplets. The pH of EG (5.57 ± 0.05 ) was found to be in accordance with the range of human skin pH. EG also illustrated efficient permeation (79.58 μL/cm2) and flux value (JSS) of 7.96 μL cm2/h through skin in 10 h. Viscosity and texture parameters, firmness (9.3 ± 0.08 g), spreadability (2.26 ± 0.06 mJ), extrudability (61.6 ± 0.05 mJ), and adhesiveness (8.66 ± 0.08 g) depict its suitability for topical application. Antimicrobial evaluation of EG with same amount of TTO as conventional gel revealed broader zones of growth inhibitions against all the selected microbial strains. Moreover, EG was also found to be nonirritant (PII 0.0833). These parameters were consistent over 90 d. Conclusion: TTO EG turned out to be a promising vehicle for the topical delivery of TTO with enhanced therapeutic efficacy.