Nanoparticulate ophthalmic drug delivery of norfloxacin to prevent ocular infection after cataract surgery: Evaluation in animal model

Post cataract surgery, patients generally experience bacterial infection called endophthalmitis which is considered as potent blinding complication. This infection arises from the colonization of Staphylococcus epidermidis on the newly implanted lense. To overcome this problem, we developed nanoparticulate ophthalmic drug delivery of Norfloxacin to prevent ocular infection after cataract surgery. Sustained release Norfloxacin loaded polymeric nanoparticles were developed by high pressure homogenization method. The nanoparticles were characterized for particle size, zeta potential, polydispersity index (PDI), encapsulation efficiency (EE), in vitro Norfloxacin release and surface characteristics using scanning electron microscopy (SEM). The optimized nanoparticulate formulation was further used for the development of thermoreversible ophthalmic gel using poloxamer polymer. The formulated ophthalmic gel was evaluated for gelation temperature, pH, bioadhesiveness, and in vitro corneal permeation study. The antibacterial efficacy testing of thermoreversible gel was assessed in animal model (rabbit) infected with Staphylococcus epidermidis. At the end of study period the inhibitory effect of thermoreversible gel was determined on test animals. The antibacterial effects were compared with control group and plain thermoreversible gel (without nanoparticle formulation). The optimized nanoparticulate formulation of Norfloxacin showed slow and gradual sustained release over the period of 72 hours, encapsulation efficiency of between 90.12 to 98.50%, particle size 95–210 nm, PDI 0.18 to 0.212 and zeta potential between 20 to 25 mV. The nanoparticles were found spherical and smooth in nature. The optimized formulation of nanoparticle was used in thermoreversible gel. The results obtained showed that the thermoreversible gel was clear and transparent (prime requirement for ophthalmic product) with high gelling capacity and moderately viscous liquid (1170 cp), highest bioadhesive strength of 2312.90 dyne/cm2. The exvivo corneal study showed excellent permeation through cornea as compare to control sample. Norfloxacin released from thermoreversible gel killed Staphylococcus epidermidis in animal models as compare to control group and showed effect up to 14 days. With these findings, we demonstrate a new and effective system for sustained drug release of Norfloxacin from thermoreversible gel with specific application to prevent ocular infection after cataract surgery.

Evaluation of the anti-biofilm effect of poloxamer-based thermoreversible gel of silver nanoparticles as a potential medication for root canal therapy

The purpose of this study was to design silver nanoparticles (AgNPs) poloxamer thermoreversible gel (AgNPs-PL) and investigate whether this gel could provide sustained antibacterial activity against Enterococcus faecalis (E. faecalis) in the root canal. The gels fabricated were characterized in terms of gelatin temperature, particle size, in-vitro Ag+ release, and elemental content. Cytotoxicity of AgNPs-PL on primary human periodontal ligament fibroblasts (HPDLFs) was examined by CCK-8 assay. Characterization of AgNPs-PL gel revealed that it contained particles existing as large clumps/fused aggregates of different shapes, with a mean diameter of 21.624 ± 14.689 nm, exhibited sustained release of Ag+ for 9 days, and non-toxic to HPDLFs at a low dose (4–32 μg/mL) through 24, 48, and 72 h exposures. The antibacterial effect of 16 and 32 μg/mL concentrations of AgNPs-PL was compared with blank poloxamer gel (PL) and calcium hydroxide (CH) using three methods: (I) agar counting plate, (II) scanning electron microscope (SEM) observations, and (III) confocal laser scanning microscope (CLSM) analysis. AgNPs-PL at the two doses above was more effective than PL and CH in removing E. faecalis biofilm at 1, 3, 9 days. Thus, AgNPs-PL exhibits strong activity against E. faecalis and is easy to produce, with a continuous release profile of Ag+. AgNPs-PL gel may be a candidate for a new root canal disinfection.

Appraisal of Nano-lipidic Astaxanthin cum Thermoreversible Gel and its Efficacy in Haloperidol Induced Parkinsonism

Background: Parkinsonism has a toxic cascade of neurodegeneration, with akinesia as a major manifestation. Some antioxidants have shown promise against the disease. Astaxanthin is a powerful antioxidant, demonstrates free radical scavenging, and is also a potential neuroprotective agent Objective: To formulate astaxanthin laden nanostructured lipid carriers based thermoreversible gel for better neuronal uptake and better neuronal efficacy. Methods: The method for fabricating astaxanthin-nanostructured lipid carriers (ATX-NLC) was melt-emulsification, and these were optimized using factorial design and further evaluated for diverse parameters. Neurotoxicity was induced in rats by haloperidol. The treated and non-treated rats were then witnessed for their behaviour. TBARs and GSH levels were also determined. Pharmacokinetics was studied via HPLC. Results: The average particle size (by DLS), entrapment efficiency and zeta potential of optimized ATX-NLC were 225.6 ± 3.04 nm, 65.91 ± 1.22 % and -52.64 mV respectively. Astaxanthin release (after 24 h in simulated nasal fluid) from optimized ATX-NLC was 92.5 ± 5.42 %. Its thermo-reversible nasal gel (ATX-NLC in-situ gel) was prepared using poloxamer-127. The obtained gel showed in-vivo betterment in the behaviour of animals when studied using rotarod and akinesia test. Pharmacokinetic studies showed better availability of astaxanthin in the brain on the rats treated with ATX-NLC in-situ gel as compared to those treated with ATX-in-situ gel. Conclusion: Astaxanthin loaded lipidic nanoparticulate gel can be a hopeful adjuvant therapy for Parkinsonism and holds scope for future studies.

Thermal stability of prepared chicken feet gelatine gel in comparison with commercial gelatines

Gelatine is, due to its functional properties, currently widely used not only in the food industry (in the production of confectionery, dairy products, canned food) but also in pharmacy (soft and hard capsules) and cosmetics (creams, lotions) where it applies its ability to form thermoreversible gel stronger than most other gelling agents. What is more, it provides further excellent properties including emulsifying, foaming, stabilizing, film-forming, water and fat binding, texturizing, thickening, and adhesive attributes which makes it a very important hydrocolloid. Gelatine is obtained from the raw material of animal tissues containing collagen, usually mammalian skin or bones. For religious reasons in some countries, pork or bovine gelatine must be replaced by an alternative form, such as poultry or fish gelatine. The quality of gelatine is assessed mostly by the strength of gelatine gel which strongly depends on ambient temperature or humidity. Extraction conditions may also significantly affect the quality of gelatine. This study examined possible changes in the strength of gelatine gels prepared from laboratory-produced chicken feet gelatine and compared them with commercially available pork and beef gelatines at temperatures of 23, 29, and 35 °C at 60 and 80% humidity. While at 23 °C thermal stability of prepared chicken gelatine was monitored higher than in commercial gelatines, experiments at 29 and 35 °C provided equivalent results for chicken and commercial gelatines. Therefore, prepared chicken gelatine offers a significant potential to become an alternative to traditional gelatines. The information about gelatine gels thermal stability is of great importance for applications not only in the food; but also in the pharmaceutical industry.

Formulation and Evaluation Thermoreversible Gel of Antifungal Agent for Treatment of Vaginal Infection

Aims: The aim this research work is to formulate and evaluate thermoreversible gel of antifungal agent Clotrimazole for treatment of vaginal infection. Place and Duration of Study: Department of Biopharmaceutics, Government College of Pharmacy, Karad, Maharashtra, India, between June 2009 and July 2010. Methodology: Different Formulations of thermoreversible gel of antifungal agent Clotrimazole were prepared by using various concentrations of ethanol, PEG 400, sodium dodecyl sulphate, polycarbophil and pluronic F 127 and pluronic F 68. The gel formulations were subjected for evaluation on the basis of rheological behaviour, mucoadhesive behaviour, in-vitro performance. Results: The results indicate that Polymers such as polycarbophil, PEG- 400 in various concentrations to prepare formulations were found to release drug for period over 12 hrs. Without getting dislodged. The formulations have satisfactory rheological behavior and their diffusion profile is comparable to the marketed gel formulation. Significant difference was observed in the rheological behavior of formulations. Gel strength, spreadability, mucoadhesive strength of formulation B and C were desirable. Drug diffusion of formulation B and C were 95.2% release after 11 hrs 98.5% release after 11 hrs, respectively which was good as compared to marketed formulation showing drug diffusion of 102.2% after 10 hrs. Conclusion: On basis of the results we concluded that developed thermoreversible gel of Clotrimazole will be better alternative to conventional dosage form Clotrimazole & will improve patient compliance.

Transdermal Delivery of Ondansetron HCl from Thermoreversible Gel Containing Nanocomposite

Background: Application of thermoreversible gel can be a solution to the low residence time of the topical dosage forms such as normal gel, ointment and cream on the skin surface. Addition of another polymer and a nanocomposite can improve the poor mechanical strength and fast drug release of poloxamer 407 (POL 407) gel. Therefore, it is essential to add xanthan gum (XG) and graphene oxide (GO, thickness 1-2 nm, lateral dimension 1-5 µm) to POL 407 gel to enhance the mechanical strength and to sustain the drug release from the gel. Methods: Thermal gel of ondansetron hydrochloride (OSH) containing nanocomposite was prepared by adopting cold method. Interaction between drug and polymers was studied using FTIR method, morphological investigation was carried out by optical and scanning electron microscopy method, and rheological study was performed employing rotational rheometer equipped with a cone/plate shear apparatus, gelation temperature by glass bottle method and ex vivo permeation study was performed with cylindrical glass diffusion cell. Skin irritation potential was measured using rat as a model animal. Results: The FTIR spectrum of the selected gel showed that there is shifting of O-H stretching vibration of a hydroxyl group from 3408.72 to 3360.49 cm-1 and appearance of a new band at 1083.01 cm-1. The spectrum of the selected gel also showed the absence of characteristic peaks of GO at 1625.49 cm- 1. This result indicated that there may be an interaction between OSH and GO and hydrogen bonding between XG and POL 407. The gelation temperature was found to be decreased with the increase in GO content from 14.1±1.21°C 13±0.97°C. SEM micrograph demonstrated the uniform dispersion and intercalation of GO sheets in the gel. All the gel formulations showed a pseudo-plastic flow. Ex vivo permeation study (for 24 hr) exhibited highest (6991.425 µg) and lowest (2133.262 µg) amount of drug release, for OG1 and OG5, respectively. This is attributed to an increase in viscosity which led to a decrease in drug permeation across the abdominal skin of rats. The OG1 formulation (without GO) showed the highest flux of 76.66 µg/cm2/h, permeability coefficient (Kp) of 5.111× 10-3 cm/h and enhancement ratio of 3.277 compared to OG5 containing highest amount (9% w/w) of GO. The selected gel was found to be physically stable and there was minimum irritation score. Conclusion: All the above results indicated that thermal gel containing nanocomposite sustained the drug release and can be considered as an alternative to the orally administered tablet of OSH.

Thermoreversible Gel-Loaded Amphotericin B for the Treatment of Dermal and Vaginal Candidiasis

The present study was designed to develop a thermoreversible gel of Pluronic (P407) loaded amphotericin B (AmB-gel) for the dermal and vaginal treatment of candidiasis. P407 was used as a copolymer to exploit potential advantages related to increasing drug concentration in the tissue layer in order to provide a local effect. Parameters including internal structure, swelling, porosity, and short-term stability were determined. In addition, drug release profile and ex vivo skin and vaginal permeation studies were carried out. Antifungal efficacy was evaluated against strains of Candida spp. and atomic force microscopy (AFM) supported the results. The tolerance of AmB-gel was studied by evaluating biomechanical properties of skin and determining the irritation level in scarified rabbit skin supported by histological analysis. Results confirmed the development of a thermoreversible AmB-gel with high porosity exhibiting Newtonian behavior at 4 °C and pseudoplasticity at 32 °C as well as optimal stability for at least 90 days. The Amb-gel provided a sustained drug release following a Boltzmann sigmoidal model. Non permeation was observed in skin and vaginal mucosa, showing a high retained amount of AmB of 960.0 and 737.3 µg/g/cm2, respectively. In vitro antifungal efficacy showed that AmB-gel was more effective than Free-AmB in inhibiting strains of Candida spp. and these results were corroborated by AFM. Finally, tolerance studies showed that its application did not induce skin irritation nor alter its biophysical properties. Together, these results confirmed that AmB-gel could be proposed as a promising candidate for the clinical status in the treatment of skin and vaginal candidiasis.

Potential Ganciclovir Liposomal Thermoreversible Gel for Ophthalmic Delivery Using Box-Behnken Statistical Design and Efficacy Assessment Study in Rabbit Model

The present study focuses on development of novel thermoreversible ophthalmic drug delivery system using Ganciclovir as potential candidate for treatment of various ocular infections. The formulation was prepared for thermoreversible gel which incorporates liposomes of Ganciclovir as core system. Thermoreversible gel prolongs delivery of drug with use of combination of polymers like Poloxamer, Hydroxypropyl methyl cellulose. The Poloxamer used here serves as temperature sensitive polymer. Thus prepared system was evaluated for various parameters. Liposomes found to be complies with basic requirement like non-leak ability, high in-vitro drug release with optimum encapsulation efficiency. The results obtained showed that the in situ gel is clear and transparent (prime requirement for ophthalmic product) with high gelling capacity and moderately viscous liquid (1454 cp), highest bioadhesive strength (Dyne/cm2). The ex-vivo study was also done and compared with marketed eye drop formulation. The results showed superiority of in situ gel formulation over eye in sustaining the drug release over prolong period of time. The haemolytic study performed proved the non-haemolytic nature of formulation.

Combinatorial Therapeutic Drug Delivery of Riboflavin and Olopetadine for the Treatment of Keratoconus Affected Corneas of Mice

The present study deals with the development and evaluation of novel thermoreversible gel containing Riboflavin and Olopatadine for the treatment of Keratoconus. The novel gel was prepared by using polymers like Poloxamer and hydroxypropyl methyl cellulose (HPMC) using cold method. The formulated system was evaluated for clarity, appearance, pH, gelling temperature, ex vivo diffusion study, Isotonicity, hemolytic study and effect in keratoconus affected mice model. The results showed that formulated gel was found to be clear and transparent having high gelling capacity. The pH was found between 6.5 to 6.9 and gelation temperature between 34 to 37 °C. All formulations were found isotonic and the hemolytic study performed proved the non-hemolytic nature of formulation. Drug content was also within acceptable limit. The F5 formulation was found to be optimized considering all evaluation parameters. F5 formulation showed maximum amount of release (98.5 and 99.6% for Ribo and Olo respectively) within 8 hrs as compare to other formulations. The effect of formulation on keratoconus affected mice showed that matrix can be produced after stimulation of KC cells and the increased thickness can be result of increase number of cells or matrix produced per cell. These results clearly conclude the potential of combinatorial therapeutic drug delivery of riboflavin and olopetadine for the treatment of keratoconus affected corneas of mice.