In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis.

Anti-psoriatic and toxicity evaluation of methotrexate loaded chitin nanogel in imiquimod induced mice model.

Methotrexate loaded chitin nanogel (MCNG) was formulated for its topical use in psoriasis. MCNG was characterized by DLS, TEM and FTIR. The MCNG particles were spherical in shape with size of 196±14nm, having surface charge of +9.21±0.42 mv. MCNG exhibited greater swelling and drug release at acidic pH than neutral and alkaline conditions. The treatment with MCNG showed significant level of toxicity on HaCaT and THP-1 cells and was taken up well by HaCaT cells as revealed by fluorescent microscopy. MCNGs exhibited significant anti-inflammatory activity as revealed by the inhibitory effects observed on the activity of COX-2 and LOX-5 enzymes expressed in THP-1 cells. Skin permeation studies revealed an increased trasdermal flux of methotrexate from MCNG with loosened stratum corneum and other epidermal layers of skin in comparison with control methotrexate solution treated samples. Significant anti-psoriatic efficacy on imiquimod (IMQ) induced model of psoriasis without any dermal and systemic toxicities suggest that it as an ideal delivery platform for topical delivery of methotrexate in psoriasis. Thus it is expected to become a better alternative for the oral delivery of methotrexate in the selected disease.

Comparative anti-psoriatic efficacy studies of clobetasol loaded chitin nanogel and marketed cream.

In the present study chitin nanogel loaded with anti-psoriatic drug clobetasol was developed (CLCNG) for its topical delivery in psoriasis. CLCNG had the particle size of 132±14nm, with gel like consistency, stability in refrigerator, having higher drug release properties at acidic pH. CLCNG exhibited significant toxicity towards HaCaT and THP-1cell lines by MTT assay. The uptake of nanogel by HaCaT cell lines was confirmed by fluorescent microscopy. CLCNG at 0.35mg/ml exhibited significant anti-inflammatory activity with an average of 65% and 70% inhibition in COX and LOX activities expressed in THP-1 cells. In vitro skin permeation studies revealed the increased transdermal flux with fragmented stratum corneum and loosened epidermal layers in CLCNG treated samples, compared with control drug solution. The in vivo anti-psoriatic studies done on imiquimod model confirmed the potential benefits of the nanogel for the topical delivery of clobetasol in psoriasis.

Acitretin and aloe-emodin loaded chitin nanogel for the treatment of psoriasis.

The present study focuses on the development of an effective topical nanogel formulation of two anti-psoriatic drugs; Acitretin (Act) and Aloe-emodin (AE) using natural polymer chitin. Simple regeneration chemistry was used to prepare Chitin Nanogel Systems (CNGs). The developed control chitin (CNGs) nanogels, acitretin loaded chitin nanogels (ActCNGs) and aloe-emodin loaded chitin nanogels (AECNGs) were characterized by DLS, SEM, FTIR, XRD and TG-DTA. The systems were found to be spherical in shape with a size range of 98±10, 138±8 and 238±6nm having zeta potential values of +28±3, +27±3 and +25±6mV for CNGs, ActCNGs and AECNGs respectively. The in vitro haemolysis assay revealed that all the nanogel systems are blood compatible. The systems exhibited higher swelling and release at acidic pH. The ex vivo skin permeation studies using porcine skin confirmed the higher deposition of the systems at epidermal and dermal layers, which was confirmed further by fluorescent imaging. The in vivo anti-psoriatic activity study using Perry's mouse tail model and skin safety studies confirmed the potential benefit of the system for topical delivery of acitretin and aloe-emodin in psoriasis.

Chitosan nanoparticles in drug therapy of infectious and inflammatory diseases.

INTRODUCTION: Chitosan, a polymer from the chitin family has diverse pharmaceutical and bio-medical utility because of its easy widespread availability, non-toxicity, biocompatibility, biodegradability, rich functionalities and high drug-loading capacity. Recent pharmaceutical research has examined the use of chitosan-based systems for drug delivery applications in various diseases. The availability of functional groups permits the conjugation of specific ligands and thus helps to target loaded drugs to the site of infection/inflammation. Slow biodegradation of chitosan permits controlled and sustained release of loaded moieties; reduces the dosing frequency and is useful for improving patient compliance in infectious drug therapy. The muco-adhesion offered by chitosan makes it an attractive candidate for anti-inflammatory drug delivery, where rapid clearance of the active moiety due to the increased tissue permeability is the major problem. The pH-dependent swelling and drug release properties of chitosan present a means of passive targeting of active drug moieties to inflammatory sites. AREAS COVERED: Development of chitosan-based nanoparticulate systems for drug delivery applications is reviewed. The current state of chitosan-based nanosystems; with particular emphasis on drug therapy in inflammatory and infectious diseases is also covered. EXPERT OPINION: The authors believe that chitosan-based nanosystems, due to the special and specific advantages, will have a promising role in the management of infectious and inflammatory diseases.

Skin and muscle permeating antibacterial nanoparticles for treating Staphylococcus aureus infected wounds.

Majority of the chronic wounds are infected with bacteria like Staphylococcus aureus (S. aureus). The deep tissue infections are difficult to treat using topical antibiotics, due to their poor tissue penetration. In order to treat S. aureus deep tissue infections we have developed an antibiotic delivery system using chitosan nanoparticles (CNPs). To enhance their tissue penetration these CNPs were further coated using lecithin (CLNPs). Antibiotic tigecycline was loaded into chitosan nanoparticles (tCNPs) and then coated with lecithin to generate lecithin coated tigecycline loaded chitosan nanoparticles (tCLNPs). The prepared nanoparticles were characterized using DLS, SEM, TEM and FT-IR. The prepared CNPs, tCNPs, CLNPs and tCLNPs have the size range of 85 ± 10, 90 ± 18, 188 ± 5 and 235 ± 20 nm, respectively. The tCLNPs shows more sustained release pattern of tigecycline. The antibacterial activity of the developed nanoparticles was confirmed against laboratory and clinical strains of S. aureus using in vitro and ex vivo experiments. The ex vivo skin and muscle permeation study ensures the enhanced delivery of tigecycline to the deeper tissue. The prepared nanoparticles were hemo-compatible and cyto-compatible. Our study suggests that the prepared tCLNPs can be effectively used for the treatment of S. aureus infected wounds.

Colloidal chitin nanogels: A plethora of applications under one shell.

Chitin nanogels (CNGs) are a relatively new class of natural polymeric nanomaterials which have a large potential in the field of drug delivery and nanotherapeutics. These nanogels being very biocompatible are non-toxic when internalized by cells. In this review various properties, preparation techniques and applications of CNGs have been described. CNGs because of their nano-size possess certain unique properties which enable them to be used in a number of biomedical applications. CNGs are prepared by simple regeneration technique without using any cross-linkers. Various polymers, drugs and fluorescent dyes can be blended or incorporated or labelled with the chitin hydrogel network. Drugs and molecules encapsulated within CNGs can be used for targeted delivery, in vivo monitoring or even for therapeutic purposes. Here various applications of CNGs in the field of drug delivery, imaging, sensing and therapeutics have been discussed.

Nanogels for delivery, imaging and therapy.

Nanogels are hydrogels having size in nanoregime, which is composed of cross-linked polymer networks. The advantages of nanogels include stimuli-responsive nature, easy drug loading, and higher drug-loading capacity, physical stability, versatility in design, stability of entrapped drug, and controlled release of the anti-inflammatory, antimicrobial, protein, peptide and anticancer drugs. Stimuli-responsive nature of nanogel is of particular importance in anticancer and anti-inflammatory drug delivery, as cancer and inflammation are associated with acidic pH, heat generation, and change in ionic content. Nanogels composed of muco-adhesive polymers provide prolonged residence time and increase the ocular availability of loaded drugs. By forming suitably sized complex with proteins or by acting as artificial chaperones, they thus help to keep the proteins and enzymes in proper confirmation necessary for exerting biological activity; nanogels can increase the stability and activity of protein/peptide drugs. Better drug penetrations achieved by prolonged contact with skin contribute much in transdermal drug delivery. When it comes to cancer drug delivery, the presence of multiple interactive functional groups in nanogels different targeting agents can be conjugated for delivery of the selective drugs. This review focuses on applications of nanogels in cancer drug delivery and imaging, anti-inflammatory, anti-psoriatic, transdermal, ocular and protein/peptide drug delivery and therapy.

Development and evaluation of 5-fluorouracil loaded chitin nanogels for treatment of skin cancer.

This study focuses on development and evaluation of 5-fluorouracil (5-FU) loaded chitin nanogels (FCNGs). It formed good, stable aqueous dispersion with spherical particles in 120-140 nm size range and showed pH responsive swelling and drug release. The FCNGs showed toxicity on melanoma (A375) in a concentration range of 0.4-2.0mg/mL, but less toxicity toward human dermal fibroblast (HDF) cells by MTT assay. Confocal analysis revealed uptake of FCNGs by both cells. From skin permeation experiments, FCNGs showed almost same steady state flux as that of control 5-FU but the retention in the deeper layers of skin was found to be 4-5 times more from FCNGs. Histopathological evaluation revealed loosening of the horny layer of epidermis by interaction of cationically charged chitin, with no observed signs of inflammation and so FCNGs can be a good option for treatment of skin cancers.

Nanotechnology in cosmetics: Opportunities and challenges.

Nanotechnology is the science of manipulating atoms and molecules in the nanoscale - 80,000 times smaller than the width of a human hair. The world market for products that contain nanomaterials is expected to reach $2.6 trillion by 2015. The use of nanotechnology has stretched across various streams of science, from electronics to medicine and has now found applications in the field of cosmetics by taking the name of nanocosmetics. This widespread influence of nanotechnology in the cosmetic industries is due to the enhanced properties attained by the particles at the nano level including color, transparency, solubility etc. The different types of nanomaterials employed in cosmetics include nanosomes, liposomes, fullerenes, solid lipid nanoparticles etc. Recently, concerns over the safety of such nanocosmetics are raised and have forced the cosmetic industries to limit the use of nanotechnology in cosmetics and for enforcing laws to undergo a full-fledged safety assessment before they enter into the market. In this review, emphasis is made on the types of nanomaterials used in cosmetics by the various cosmetic brands, the potential risks caused by them both to human life and also to the environment and what all regulations have been undertaken or can be taken to overcome them.

Synthesis, characterization and in vitro cytocompatibility studies of chitin nanogels for biomedical applications.

In this work we developed biodegradable chitin nanogels (CNGs) of size 65nm by controlled regeneration method and characterized. The CNGs showed higher swelling and degradation in acidic pH. The in vitro cytocompatibility was analyzed on an array of cell lines and cell uptake studies were done by conjugating CNGs with the rhodamine-123 dye (rhodamine-123-CNGs), which showed retention of nanogels inside the cells. Our preliminary studies reveal that these nanogels could be useful for the delivery of drugs, growth factors for drug delivery and tissue engineering.

Development and characterization of transdermal drug delivery systems for diltiazem hydrochloride.

Transdermal drug delivery system of diltiazem hydrochloride was developed to obtain a prolonged controlled drug delivery. Both the matrix diffusion controlled (MDC) and membrane permeation controlled (MPC) systems were developed. The matrix diffusion controlled systems used various combinations of hydrophilic and lipophillic polymers, whereas membrane permeation controlled systems were developed using the natural polymer chitosan. The MDC systems were prepared using the cast film method and the MPC systems by an adhesive sealing technique. Both the systems were characterized for in vitro and in vivo performance. The MDC systems were characterized for physicochemical properties such as tensile strength, moisture content, and water vapor transmission. The in vitro release studies showed that the release from the matrix diffusion controlled transdermal drug delivery systems follows a nonfickian pattern and that from the membrane permeation controlled transdermal drug delivery systems follow zero-order kinetics. The release from the matrix systems increased on increasing the hydrophilic polymer concentration, but the release from the membrane systems decrease on cross-linking of the rate controlling membrane and also on addition of citric acid to the chitosan drug reservoir gel. The in vivo studies of the selected systems showed that both systems are capable of achieving the effective plasma concentration for a prolonged period of time. The MPC system achieved effective plasma concentration a little more slowly than the MDC system, but it exhibited a more steady state plasma level for 24 hr.