Development and in vitro evaluation of polar lipid based lipospheres for oral delivery of peptide drugs

A 32 factorial design was employed to produce oral sustained release lipospheres prepared by modified double emulsion solvent evaporation technique for Serratiopeptidase (acid-labile enzyme) using wax and polar lipid combination as retardants. The effects of formulation variables selected through preliminary trials namely peptide and stabilizer (Tween® 80) concentration was evaluated by F-test on the drug content and size of lipospheres. The results of analysis of variance tests for both effects indicated that the test is significant (p < 0.05). The effect of Tween® 80 concentration (SSY1- 41.66; SSY2 – 25.30) was found to be higher than peptide amount (SSY1- 3.94; SSY2 – 4.03) on the size and drug content of lipospheres. Characterization was carried out through photomicroscopy, scanning electron microscopy, particle size analysis and in vitro drug release study. The effect of formulation variables on the integrity of enzyme was confirmed by in vitro proteolytic activity. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion and Ritger-Peppas model. Lipospheres having maximum drug content (11.93±0.89) released 3-4% enzyme at pH 1.2 in 4 h. In phosphate buffer, lipospheres showed an initial burst release of 20.89±1.87% to 27.89±2.03% in one hour with additional 73.22±2.36% to 94.75±2.78% in next 12 hours. Thus, peptide loaded lipospheres with desirable characters in terms of maximum peptide content and diffusion release pattern were successfully prepared with formulation optimization approach.Keywords: Cetyl alcohol, Enzyme, factorial design, Lipospheres; Peptide, Serratiopeptidas

Development and in vitro evaluation of polar lipid based lipospheres for oral delivery of peptide drugs

A 32 factorial design was employed to produce oral sustained release lipospheres prepared by modified double emulsion solvent evaporation technique for Serratiopeptidase (acid-labile enzyme) using wax and polar lipid combination as retardants. The effects of formulation variables selected through preliminary trials namely peptide and stabilizer (Tween® 80) concentration was evaluated by F-test on the drug content and size of lipospheres. The results of analysis of variance tests for both effects indicated that the test is significant (p < 0.05). The effect of Tween® 80 concentration (SSY1- 41.66; SSY2 – 25.30) was found to be higher than peptide amount (SSY1- 3.94; SSY2 – 4.03) on the size and drug content of lipospheres. Characterization was carried out through photomicroscopy, scanning electron microscopy, particle size analysis and in vitro drug release study. The effect of formulation variables on the integrity of enzyme was confirmed by in vitro proteolytic activity. The drug release from lipospheres followed first-order kinetics and was characterized by the Higuchi diffusion and Ritger-Peppas model. Lipospheres having maximum drug content (11.93±0.89) released 3-4% enzyme at pH 1.2 in 4 h. In phosphate buffer, lipospheres showed an initial burst release of 20.89±1.87% to 27.89±2.03% in one hour with additional 73.22±2.36% to 94.75±2.78% in next 12 hours. Thus, peptide loaded lipospheres with desirable characters in terms of maximum peptide content and diffusion release pattern were successfully prepared with formulation optimization approach.Keywords: Cetyl alcohol, Enzyme, factorial design, Lipospheres; Peptide, Serratiopeptidas

Formulation and optimization of Retapamulin loaded PLGA nanoparticles for burn wounds

In the present study, PLGA nanoparticles (PLGA-NP) of retapamulin (RP) were prepared and optimized by studying the effect of various formulation and process variables for effective delivery at burn wound site. Drug loaded PLGA-NP were successfully prepared and characterized by TEM, XRD and DSC study. Formulation and process variables like surfactant concentration, drug concentration, polymer concentration etc. showed significant effect on the particle size, entrapment efficiency and drug loading. PLGA-NP exhibited prolonged drug release following Higuchi release kinetics (R2= 0.9907). In vitro study demonstrated systemic escape of drug from PLGA-NP which might eliminate side effects associated with topical exposure through conventional treatment. Further retention of activity of entrapped drug was confirmed by in vitro antimicrobial assay. Optimized PLGA nanoparticle of Retapamulin was incorporated into PVA-Chitosan hydrogel slurry and casted into film to prepare multiphase hydrogel.Thus, present optimized system can be effectively used for delivery of drug at burn wound site in especially compromised wounds.&nbsp

Inflammatory bowel disease: pathogenesis, causative factors, issues, drug treatment strategies, and delivery approaches

Inflammatory bowel disease (IBD) is an incessant, reverting, inflammatory disorder of the gastrointestinal tract encompassing two entities, namely, Crohn\u27s disease (CD) and ulcerative colitis (UC). Numerous protocols have been explored to treat these dreadful diseases, including the use of different IBD drugs with different modes of action and routes of administration. Constant progression in the development of newer formulations, chemical modifications, stimuli-responsive systems, and novel approaches using colloidal and cellular carriers have led to effective treatments of gastric inflammation. Colloidal carriers including vesicular and particulate systems such as liposomes, transferosomes, solid lipid nanoparticles, microspheres; cellular carriers including erythrocytes, macrophages, and recombinant bacteria; and other systems such as osmotic pressure and plug control release have gained unique positions as drug carriers. Here, we investigate IBD in terms of its pathogenesis, role of genetic factors, currently available treatment options and their modes of action, pharmacokinetics, marketed products, side effects of individual IBD drugs, recent developments, modifications in the delivery of various drugs through novel colloidal drug carriers, and future prospects

Bioremediation of hazardous azo dye methyl red by a newly isolated <i>Bacillus megaterium</i> ITBHU01: Process improvement through ANN-GA based synergistic approach

112-125Methyl red (MR), a commonly used azo dye, poses serious environmental consequences due to its toxic, recalcitrant and refractory nature. In the current study, a bacterial isolate, ITBHU01, with remarkable characteristics to decolourize MR dye, was characterized by its phenotypic features and phylogeny using fatty acid methyl ester (FAME) profiling and 16S rDNA sequence homology. At artificial neural network linked genetic algorithm (ANN-GA) based optimal conditions of parameters viz., initial MR concentration of 258.54 mg/L, pH of 7.21, the temperature of 38.2°C, and salinity of 26.3 g/L, the maximum decolourization of 98.1% was obtainedby static incubation of 24 h. FTIR spectra revealed the bacterial degradation of MR dye by cleavage of azo bonds present in the dye. ESI-MS analyses have shown formation of two prime metabolic products as N,N-dimethyl-p-phenylenediamine and 2-aminobenzoic acid indicating the symmetric cleavage of azo (–N=N–) bond; however, the presence of additional peaks illustrated about the formation of different other metabolites also. Purified azoreductase with a molecular weight of 28.0±0.2 kDa was found primarily responsible for reductive cleavage of azo bond leading to biodegradation of MR. Phytotoxicity assay for bacterial treated dye on seeds of Solanum lycopersicum, Sorghum bicolor and Triticum aestivum had significantly shown that there was no inhibition in their seed germination confirming the non-toxic nature of degraded metabolites

Novel Biotherapeutics Targeting Biomolecular and Cellular Approaches in Diabetic Wound Healing

Wound healing responses play a major role in chronic inflammation, which affects millions of people around the world. One of the daunting tasks of creating a wound-healing drug is finding equilibrium in the inflammatory cascade. In this study, the molecular and cellular mechanisms to regulate wound healing are explained, and recent research is addressed that demonstrates the molecular and cellular events during diabetic wound healing. Moreover, a range of factors or agents that facilitate wound healing have also been investigated as possible targets for successful treatment. It also summarises the various advances in research findings that have revealed promising molecular targets in the fields of therapy and diagnosis of cellular physiology and pathology of wound healing, such as neuropeptides, substance P, T cell immune response cDNA 7, miRNA, and treprostinil growth factors such as fibroblast growth factor, including thymosin beta 4, and immunomodulators as major therapeutic targets