Drug Delivery Letters - Volume 9, Issue 2, 2019

Introduction: The design of advanced drug delivery systems based on synthetic and supramolecular chemistry has been very successful. Liposomal doxorubicin (Caelyx®), and liposomal daunorubicin (DaunoXome®), estradiol topical emulsion (EstrasorbTM) as well as soluble or erodible polymer systems such as pegaspargase (Oncaspar®) or goserelin acetate (Zoladex®) represent considerable achievements. Discussion: As deliverables have evolved from low molecular weight drugs to biologics (currently representing approximately 30% of the market), so too have the demands made of advanced drug delivery technology. In parallel, the field of membrane trafficking (and endocytosis) has also matured. The trafficking of specific receptors i.e. material to be recycled or destroyed, as well as the trafficking of protein toxins has been well characterized. This, in conjunction with an ability to engineer synthetic, recombinant proteins provides several possibilities. Conclusion: The first is using recombinant proteins as drugs i.e. denileukin diftitox (Ontak®) or agalsidase beta (Fabrazyme®). The second is the opportunity to use protein toxin architecture to reach targets that are not normally accessible. This may be achieved by grafting regulatory domains from multiple species to form synthetic proteins, engineered to do multiple jobs. Examples include access to the nucleocytosolic compartment. Herein, the use of synthetic proteins for drug delivery has been reviewed.

Aim: The aim of this investigation was to develop and characterize naproxen loaded chitosan nanoparticles by emulsion interfacial reaction method. Methodology: For emulsion interfacial reaction method chitosan was used as a polymer. In this method, eight formulations were prepared by varying drug to polymer concentration. Discussion: Out of eight formulations prepared using emulsion interfacial reaction method EI8 formulation was found to be the best formulation. The drug content was observed as 94.4%, entrapment efficiency and loading capacity were found to be 87.5% and 75%, respectively. The mean particle diameter was measured as 324.6nm and the Zeta potential value was found to be -42.4mv. In vitro drug release data showed 97.2% of drug release rate sustained up to 12hrs. Conclusion: The results clearly reveal that EI8 formulation having the highest amount of drug was considered as the best formulation because of its small mean particle diameter, good entrapment efficiency, and stability.

Background: Levans are biopolymers of fructose, produced by different microorganisms. Fructose present in the levan micelles binds with the Glucose Transporter 5 (GLUT 5) which is overexpressed in the breast cancer cells. Objective: Increased solubility of paclitaxel by loading in the GLUT 5 transporter targeted levan-based micelles may enhance its bioavailability and facilitate a targeted delivery to the breast cancer cells. Methods and Results: Critical micelle concentration of levan with an average molecular weight of 800,000 Dalton was found to be 0.125μM corresponding to 0.1mg/mL using pyrene I3/I1 method. At critical micelle concentration (CMC), levan formed very mono-disperse (PDI-0.082) micellar particles with a particle size of 153.1 ± 2.31nm and -14.6 ± 2mV zeta potential. In-vitro drug release study was performed to identify the fit kinetic model along with Fourier transform infrared analysis and Differential scanning calorimetry studies. In-vitro kinetic model fitting revealed first-order drug release from the prepared micellar composition. The drug-loaded micellar composition was studied for its anticancer activity in breast cancer cell line. The IC50 value obtained was 1.525 ± 0.11nM on MCF7 cell line. Conclusion: Paclitaxel micelles showed a nineteen-fold improvement in the IC50 value compared to free paclitaxel. Hemocompatibility study was performed with a view to parenteral administration. This solution containing drug was found to be hemocompatible when added to bovine blood in 1:4 ration. Micelles are proven fairly compatible on the basis of hemolysis test results.

Objective: The presence of capsaicin in the diet has been revealed to enhance energy expenditure and it has been used in anti-obesity therapy. The present work investigated the potential antihyperlipidemic effect of capsaicin loaded hydrogel beads on hyperlipidemic rats. Hydrogels are three dimensional, hydrophilic, polymeric networks capable of imbibing large amounts of water or biological fluids. Methods: Capsaicin loaded hydrogel beads were prepared by the ionotropic gelation method using Aluminium Chloride (AlCl130;ƒ) as a cross-linking agent. The characterization of hydrogel beads was carried out by X-ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopic (SEM) analysis. Results: The surface morphology revealed that the prepared beads were spherical in shape. XRD and DSC study of the hydrogel beads revealed that the drug was homogeneously dispersed in the hydrogel matrix. The beads showed pH sensitive behavior and when the medium pH was changed from 1.2 to 7.4, the capsaicin release was considerably increased. 100mg/kg body weight of Triton was injected intraperitoneally in rats to induce hyperlipidemia and it showed elevated levels of serum cholesterol and triglyceride. Capsaicin loaded hydrogel beads were administered to normal and hyperlipidemic rats for 7 days and the prepared hydrogel beads were significantly reduced high lipid profile in comparison to free capsaicin. Conclusion: The results clearly demonstrated that hydrogel beads can be used as a potential carrier for delivery of capsaicin to reduce lipid profile.

Background: Herbal extracts have brilliant in-vitro activity but less in-vivo action in light of their macromolecular size and poor lipid solubility bringing about poor absorption and low bioavailability. These issues can be corrected by designing novel drug delivery systems. Phytosomes provide better absorption and bioavailability when compared to conventional herbal extract. Objective: This paper deals with the preparation, optimization and characterization of Phytosome of plant extract and in vivo assessment of antidiabetic and antihyperlipidemic activity for improved therapeutic efficacy having sufficient stability. Methods: Preliminary distinctive strategies were utilized to get ready Phytosome and antisolvent precipitation method was chosen. The formulation was guided by a full factorial design to study the effect of Independent variable on various dependent variables and resulted in an optimised product. Response contour plots were generated for each response factor to predict a phytosomal composition that yields phytosome formulation having least particle size and maximum entrapment efficiency. Results: Mean particle size, entrapment efficiency and Span value were found to be 295 ± 0.53nm, 82.43 ± 1.65% and 0.34 ± 0.14 respectively. Zeta potential was found to be 19.35mv, indicating the formation of stable formulation. In vitro release study described that the drug release follows the Korsmeyer- Peppas kinetic model. The results proved that Phytosomes of Casuarina equisetifolia extract exhibited more antidiabetic potential and antihyperlipidemic properties as compared to crude Casuarina extract. Conclusion: Phytosomes of Casuarina equestifolia extract was successfully formulated having good entrapment efficiency and physico-chemical characterization of the optimized product, confirming the formation of stable formulation. In vivo antidiabetic activity confirmed better potential of the optimised formulation. Consequently, it has been presumed that Phytosomes of Casuarina equisetifolia extract serve as a useful novel drug delivery system and provide more therapeutic efficacy than conventional plant extracts

Background: The skin-PAMPA test is a quick and relatively deep tool in the early stages of drug discovery and formulation of dermal and transdermal delivery systems. Objective: This study focused on the application of the skin-PAMPA test to evaluate the permeation of Resveratrol (RSV) and also of two formulations, Liposomes (LP) and Nanostructured Lipid Carriers (NLC), prepared to improve RSV topical delivery. Methods: LP and NLC were physically and chemically characterized. Stability and in vitro release studies were also assessed in different pH media. The release results were applied to define the kinetic and mechanism of RSV release from the LP and NLC formulations. In vitro permeability was estimated through the skin-PAMPA and the antioxidant capacity was evaluated by DPPH test. Results: Nanoparticles have a spherical shape, dimensions suitable for skin application, and narrow size distribution. Encapsulation efficiency was 96.5% ± 2.1 for LP and 86.0% ± 2.4 for NLC. The formulations increased RSV solubility. Nanoparticles showed excellent physical and chemical stability during storage at 4°C for two months. In vitro release studies were performed at pH 5.5 and 7.4. The nanoparticles achieved a prolonged release of RSV. Skin-PAMPA proved an increased cutaneous permeability of RSV when loaded into LP or NLC. Both formulations maintained the antioxidant capacity of RSV, as evidenced by DPPH test. Conclusion: LP and NLC could be applied as drug delivery systems suitable for the topical delivery of the RSV. Skin-PAMPA has proved to be an effective tool for studying the permeability not only of the RSV but also of its formulations.

Objective: The main objective of the study was to develop gliptin loaded polymeric nanomicelles by direct dissolution method. The comparative evaluation studies were performed to study the effect of polymer concentration on particle size, entrapment efficiency, loading capacity and drug release of the formulation. Methods: Gliptin loaded polymeric nanomicelles were prepared by the direct dissolution method. The formulations were prepared by varying the concentration of polymer and drug concentration was kept constant in all the formulations. The concentration of polymer (pullulan) was maintained 0.1%, 0.5% 1% in formulation F-1, F-2 and F-3, respectively. The effect of polymer concentration on mean particle size, zeta potential, % entrapment efficiency, % loading capacity and in vitro drug release was studied. Results: The optimized nanoformulation was obtained with pullulan 0.1% concentration with a mean particle diameter of 368.2nm and zeta potential value (-7.96mV) indicating greater stability. Conclusion: Hence F-1 was considered to be the best formulation for the preparation of gliptin loaded polymeric nanomicelles. Hence, it can be concluded that polymeric nanomicellar approach can be beneficial to improve the bioavailability and poor permeability of class III drugs like gliptins and thus can be a better approach for controlled drug delivery.

Background: The poor solubility of a drug substance is one of the factors which are responsible for poor dissolution and bioavailabity. Objective: To enhance the solubility of Ibuprofen using different techniques, and to investigate the effect of carrier matrixes and methods of preparing solid dispersion on physical state and solubility of Ibuprofen. Methods: Fusion method, solvent evaporation and effervescence assisted fusion methods were used to prepare solid dispersions of ibuprofen (IBU). Mannitol, polyethylene-glycol-6000, urea, microcrystalline cellulose, calcium carbonate, sugar spheres, sodium chloride, magnesium oxide, titanium dioxide, citric acid, hydroxypropyl-β-cyclodextrin and β-cyclodextrin were used as carrier matrix. Solid dispersions were characterized using scanning electron microscopy and Differential Scanning Calorimetry (DSC). The solubility of IBU powder and its solid dispersions were investigated in water, acidic buffer (pH-1.2) and in phosphate buffer (pH-6.8). Results: In some of the solid dispersions, IBU lost its crystalline structure and converted into amorphous powder. Scanning electron micrographs and DSC thermograms revealed the absence of IBU crystalline particles in few of the solid dispersion matrixes. Solid dispersion comprising amorphous IBU showed remarkable enhancement in its solubility. The IBU-magnesium oxide solid dispersion showed the highest solubility enhancement, followed by IBU-hydroxypropyl-β-cyclodextrin, IBUpolyethylene glycol-6000, IBU-urea and IBU-β-cyclodextrin. The magnesium oxide, hydroxypropyl-β- cyclodextrin and β-cyclodextrin enhanced solubility even at acidic pH. Effervescence assisted fusion technique showed better solubility results than the other two techniques. Conclusions: On the basis of present observations, it can be suggested that the type of carrier matrix, the method of preparation and the pH of the dispersion plays an important role in the solubility of IBU.