Wound Healing –A Review of Novel Therapeutic Strategies

New ideas on controlling the pharmacokinetics, pharmacodynamics, nonspecific toxicity, immunogenicity and efficiency of drugs have generated new strategies, often called as the drug delivery system. Development of an existing drug molecule can significantly improve its performance in terms of patient compliance, safety, and efficacy from a conventional form to a novel delivery system can significantly improve . The variety of dressings based on types of wounds and novel polymers used for the delivery of drugs to acute and chronic wound has resulted in a wide range of new products frequently introduced to target different aspects of the wound healing process. These include hydrocolloids, alginates, hydrogels, polyurethane, collagen, chitosan, pectin and hyaluronic acid. Nevertheless, nanofibers with their physicochemical properties and nanotopography display improvements in the fields of tissue engineering, wound therapy and drug delivery systems. At present, there are so many existing drug delivery technologies that a total compilation is not within the scope of this article. Yet an attempt is being made to compile some of the most successfully marketed drug delivery technologies. This review extends the information and hopes to give insight into past, present and future strategies and approaches for wound healing managements

Development and characterization of Antiemetic patch comprising Granisetron

The skin can be used as the site for drug administration for continuous transdermal drug infusion into the systemic circulation. For the continuous diffusion/penetration of the drugs through the intact skin surface membrane-moderated systems, matrix dispersion type systems, adhesive diffusion controlled systems and micro reservoir systems have been developed. Various penetration enhancers are used for the drug diffusion through skin. In matrix dispersion type systems, the drug is dispersed in the solvent along with the polymers and solvent allowed to evaporate forming a homogeneous drug-polymer matrix.Matrix type systems were developed in the present study. In the present work, an attempt has been made to develop a matrix-type transdermal therapeutic system comprising of Granisetron -HCl with different ratios of hydrophilic and hydrophobic polymeric combinations using solvent evaporation technique. The physicochemical compatibility of the drug and the polymers was studied by infrared spectroscopy. The results obtained showed no physical-chemical incompatibility between the drug and the polymers. The patches were further subjected to various physical evaluations along with the in-vitro permeation studies using rat skin. On the basis of results obtained form the in-vitro study and physical evaluation the patches containing hydrophilic polymers i.e. polyvinyl alcohol and poly vinyl pyrrolidone, with oleic acid as the penetration enhancer(5%) were considered as suitable for large scale manufacturing with a backing layer and a suitable adhesive membrane

Preparation and Evaluation of 5 Fluorouracil solid dispersion formulations for therapeutic management of colorectal cancer (CRC)

BackgroundA solid dispersion formulation (SD) involves dispersion of poor water soluble active pharmaceutical ingredients (API) in a solubility enhancing polymer with the uttermost goal of improving the oral bioavailability of the API.ObjectiveThis study is aimed at production and evaluation of 5- Fluorouracil (5- FU) SD formulations for colon delivery using the hot met technique.MethodThe solid dispersions of 5-FU were prepared by hot melting method; The  SD formulations were characterized using a scanning electron microscopy, USP dissolution apparatus type 2, and  MTT assay.ResultsThe SEM revealed that all SD formulations particles were in amorphous state, they rod like shaped with size ranging between 98 -112µm. The FTIR spectral show no chemical interactions between the excipients and 5 FU.  The yield (PY), drug entrapment efficiency (DEE) and the drug loading (DL) values were high enough to support commercial scale up of the technique.SD2 had the highest DEE, cumulative drug released and DL values. This may be responsive for its improved cytotoxicity against HT115 cells. The releases of 5 FU in all the formulations follow both Fickian´s and non-Fickian´s kinetics which are also pH responsive with no sign of dose dumping. ConclusionThis study demonstrated successful production of pH responsive 5 FU solid dispersions, by hot melt technique. The release follows Korymeyer –Peppas kinetic models and selectively delivered 5 FU to the colon which improved cytotoxicity activity against CRC

Gastro-protective effect of some statins against induced gastric ulcer in rats

Abstract Background & Objective: The objective of the present study was to evaluate the effect of different statins (HMG-CoA reductase inhibitors) on gastric and duodenal ulcer in rats. Methods: The effect of different statins on gastric and duodenal ulcers were evaluated by using different experimental models such as acetic acid induced chronic gastric ulcer, pylorus ligation induced gastric ulcer, ethanol induced gastric ulcer, stress induced gastric ulcer and cysteamine induced duodenal ulcer. Results: The different statins tested in the present showed variable effects in different models of gastric ulcers and cysteamine induced duodenal ulcer. Atorvastain showed anti-ulcer activity in three models; pylorus ligation, ethanol induced gastric ulcer and acetic acid induced chronic gastric ulcers. Simvastatin showed a decrease in free acidity in pylorus ligated rats while lovastatin did not influence gastric and duodenal ulcer formation or healing of gastric ulcers. Interpretation & Conclusion: The atorvastatin showed significant effect on the healing and development of gastric ulcers while other statins did not influence ulcer healing or ulcer formation. It was concluded atorvastatin possess anti-ulcer effect in rats and all the tested statins may be safe for administration to patients suffering from peptic ulcer disease

Evaluation of anti-hyperlipidemic activity in high fat diet induced hyperlipidemic rats of Carissa carandas (Auct.) leaves extract

Hyperlipidemia contributes significantly in the manifestation and development of atherosclerosis and heart disease. Although synthetic lipid‑lowering drugs are useful in treating hyperlipidemia, there are number of adverse effects. Therefore, the current interest has stimulated the search for new lipid‑lowering agents with minimal side effects from natural sources. The Purpose of this study was to examine the lipid lowering capability of aqueous: ethanol (1:1) extract of Carissa carandas in high fat diet induced hyperlipidemic rats. A highly significant increase in the weight of high cholesterol diet rats was observed when compared with control group (P<0.01). The extract caused a significant reduction in body weight, Cholesterol, Triglycerides, HDL and LDL in hyperlipidemic rats. Histopathological changes induced by high cholesterol diet were also significantly reduced by the extract. The activity of ethanol and water extract of C. carandas was comparable to that of atorvastatin.

Acridone-based acetylcholinesterase inhibitors: synthesis, antioxidant activity and molecular modeling

Acridone is a unique naturally occurring alkaloid known to associate with several biological activities. 2,3-dimethoxy-10-methyl-10,8a-dihydroacridin-9(8aH)-one (4) and its precursor 2-((3,4-dimethoxyphenyl)methylamino)benzoic acid (3) were synthesized and investigated for potential antioxidant and inhibitory activity against acetylcholinestrase. The synthetic pathway involves reaction of 2-(methylamino) benzoic acid (1) with 4-chloro-1,2-dimethoxybenzene (2) in presence of CuO and K2CO3 to give the precursor 3. Subsequent, cyclcondensation of 3 with Conc. H2SO4 afforded the anticipated acridone 4. Furthermore, the dimethoxyacridone derivative 4 showed potent antiacetylcholinesterase (ACHE) activity at (100 uM) with IC50 = 9.25 uM that is as potent as the reference drug rivastigmine. Assessment of total antioxidant activity of compounds 3 & 4 in comparison to known standard compounds revealed the following order: α-tocopherol > Acridone 4 > trolox > butylated hydroxyl anisole (BHA) > butylated hydroxyl toluene (BHT) > compound 3. Molecular docking characteristics of 3 & 4 within the active site of AChE (PDB: 1ACJ) co-crystallized with 9-amino-tetrahydroacridine (Tacrine) have been studied. Interestingly, the results revealed comparable binding poses to the co-crystallized ligand and demonstrates good correlation of the binding energy (DG) with the observed IC50-values. This finding suggests that compounds 3 & 4 exhibit good antioxidant effect and inhibition of acetylcholinesterase, which might provide profitable candidates in management of Alzheimer’s disease

Formulation, Optimization and Evaluation of Self Emulsifying Immediate Release Tablet of Nebivolol HCl using 32 Factorial Design

Nebivolol Hydrochloride (NEB) is a lipophilic molecule with low solubility in GI fluid, and high metabolism which leads to its low oral bioavailability 12%. The aim of the present investigation was to develop immediate release self emulsifying tablet (IR-SET) as solid SMEDDS to enhance the solubility and permeability of the drug. Solubility study, pseudo-ternary phase diagrams and 32 factorial design were used to select the components of the system and optimize the composition of liquid SMEDDS. Optimal L-SMEDDS contains Kollisolv GTA, Tween 80 and Propylene glycol as oil, surfactant and co-surfactant, respectively in the ratio of 20:26.66:53.34 % w/w, formulates L-SMEDDS with droplet size (55.98 nm), PDI (0.37), emulsification time (16±1.52 sec) and drug content (97.43±0.30 %).  The liquid SMEDDS were adsorbed onto Neusilin US2 by adsorbtion technique to form S-SMEDDS. DSC and SEM studies suggested that NEB in the S-SMEDDS may be present in the molecular dispersed state and was sufficiently adsorbed onto solid carrier, respectively. S-SMEDDS was compressed into IR-SET by direct compression method and composition of IR-SET was optimized using 32 factorial design. Optimal IR-SET showed disintegration time (92 + 0.57 sec), droplet size (68.57 nm), PDI (0.34) and drug content (96.33±0.15 %). In vitro dissolution studies and ex vivo diffusion studies in rat stomach suggested that SMEDDS played an important role in solubility and permeability enhancing effect. Accelerated stability studies indicated that formulation were stable. Our results illustrated the increase in solubility and permeability of drug from IR-SET

In vitro evaluation of Transdermal Patch of Palonosetron for Antiemetic Therapy

Skin is one of the routes for systemic delivery of drugs through various drug delivery system. A transdermal Drug Delivery System (TDDS) is one of the most reliable and useful system to deliver drug systemically through skin. Generally medicated patch is placed on skin for delivery of medication through it into the blood stream. The aim of present study was to formulate and evaluate Palonosetron transdermal patch in vitro that could be used for antiemetic therapy. The incorporation ofPalonosetron a serotonin 5-HT3 antagonist drug was envisaged. The TDDS was prepared by solvent evaporation technique and was evaluated for organoleptic characteristics and other physicochemical properties Thickness, Weight variation, Drug content uniformity, Tensile strength, % Elongation, Folding endurance & Moisture content. The in vitro permeation study of the patch was carried out through KesaryChein diffusion cell as barrier membrane. Phosphate buffer pH 7.4 was used as dissolution medium and the temperature was maintained at 37 ± 10C. The in vitro permeation study of the prepared patch indicated a time dependent increase in drug release throughout the study. The percentage of cumulative drug release was found to be 76.25% in 24 hours.The study shows a new approach to work in with Palonosetron

Itraconazole loaded ethosomal gel system for efficient treatment of skin cancer

Topical application of Itraconazole for the treatment of Basal cell carcinoma represents a new hope in dermatology. Itraconazole for treatment of Basal cell carcinoma is an alternative therapeutic approach for the efficacious treatment of nonmelanoma skin cancer. Itraconazole loaded ethosomes were prepared and characterized by vesicular shape, vesicular size, entrapment efficiency. Ethosomal gel were prepared and characterized by pH, viscosity, washability, spreadibility, drug content, drug release study, stability study, in vivo skin tolerability and antiproliferative activity. Transmission Electron Microscopy (TEM), and Dynamic Light Scattering (DLS) characterise ethosomes as spherical, unilamellar structures having low polydispersity (0.384 ± 0.037) and nanometric size range (169.0 ± 49.0), % Entrapment efficiency of Itraconazole in ethosomal carrier was found to be 82.00 ± 1.78. Ethosomal gel were prepared by using Carbopol. The viscosity was found to be in the range of 1600±1.72 to 1740±1.73 cps. The spreadability was found to be in the range of 6.4g.cm/sec. The drug content of the ethosomal gel formulations ranged from 0.384-0.386 mg/gm. The value of steady-state transdermal flux was observed to be 54.2 ± 1.46 µg/h/cm with a lag time of 1.2 hrs with formulation EG1. Stability studies revealed no noticeable changes in drug release profile occurred. Skin irritation study on rabbit skin suggested that ethosomal gel may offer a suitable approach for transdermal delivery of Itraconazole. The further, antiproliferative study shows that Itraconazole loaded ethosomes is significantly more toxic than the free drug on BCC1/KMC cell line, thus making it a potential alternative to the standard therapy

Preparation of cyclodextrin nanoparticles and evaluation of its effect on the capacitation of bovine spermatozoa used in the in vitro fertilization

This study was conducted to produce nanosized cyclodextrin (NCD) and assess its effect on bovine spermatozoa during In vitro fertilization (IVF) to optimize the capacitation media for successful IVF. Therefore, Four cyclodextrin formulations were prepared and characterized. Data analysis revealed the best formula (F2) showed a smallest particle size (15 nm), zeta potential (-37 mv), and higher yield percentages (95%) was selected for spem capacitation. Motile spermatozoa were separated from frozen-thawed semen by a swim-up procedure and capacitated in IVF-TALP medium with different formulae of NCD or CD or without treatments (control) and incubated for 3hours(hr) at 38°C and evaluated every one (hr) interval. Data analysis revealed that the formulation of cyclodextrin nanoparticles (F2) after (2hr) incubation in the media gave best effect on sperm capacitation and acrosme reaction (AR) and effect of sperm treated with NCD on fertilization rate was evaluated. The results showed that the proportion of Oocytes fertilized was increased significantly in F2 (60%) than in the control (35%), and cyclodextrin group (50%) groups (p<0.05). It could be inferred from this investigation that cyclodextrin nanoparticles can be used for biomedical interventions in bovine spermatozoa. NCD improve sperm motility, viability, and (AR), also fertilization rate of sperm treated with NCD increase. So NCD gave positive effect on sperm functions during IVF.