Drug Delivery Letters - Volume 10, Issue 1, 2020

Background & Objectives: Stents have been effectively used in the treatment of vascular diseases and further explorations are going on in treating various strictures including tracheal, intestinal, nasal, urethra and esophageal. Stents serve as a support to walls of the lumen to prevent restenosis. Metal stents prevent in-stent restenosis but the corrosion of the metallic framework causes further complications. To overcome the shortcomings of metallic stents, metallic Drug-Eluting Stents (DES) have been designed where the drugs are chosen as an anti-restenosis agent in such a way that it prevents thrombosis, neointimal proliferation and possess immunosuppressive properties. Biodegradable stents are becoming ideal, provided they effectively spot the target stricture and have long-term stability to support the walls of the body conduit which in turn aids in eliminating the need for a second surgery. Polymeric materials can be used to enhance the mechanical strength and prolong the degradation time of biodegradable DES, thereby making it an ideal choice for stenting. Discussion: This review focus on the progress made in the design, manufacture, characterization studies and applications of stents over the past decade. Conclusion: We concluded that the use of stents is now an emerging technique for the treatment of GI strictures caused due to colorectal cancer, esophageal cancer, cholangiocarcinoma, Crohn’s disease etc. Though BDS have several advantages, advanced techniques are needed for fabrication and suitable modification in the design of the scaffold to enhance its clinical efficacy and to thereby develop an ideal endoprosthetic device.

Background: Most liposomes problems are due to stability and consistency. Proliposomes is one of the solutions to overcome the disadvantage of liposomes. They are available in dry powder form, it is easy to distribute, transfer, measure and store. Objective: The aim of the present study was to find a novel method of preparing Silymarin proliposomes and study the effect of cholesterol concentrations and surfactant types on the physicochemical properties of silymarin proliposomes and its in-vitro release. Methods: Silymarin proliposomes were prepared by combining two simple methods ethanol injection method for liposomes preparation followed by the spray drying method to get a dry powder. The physicochemical properties including particle size, TEM, SEM, FTIR, encapsulation efficiency and dissolution studies were studied. Results: The particle size of silymarin liposomes were below 552.36 ± 17.63 nm but after reconstitution of silymarin proliposomes, the particle size was in the micro range due to the influence of the spray drying process. Cholesterol concentration was ranged from 50 to 150 mg per formula. Increasing Cholesterol concentration caused a significant increase in liposomes particle size and reduction in encapsulation efficiency. Three non-ionic surfactants were used to prepare silymarin proliposomes Tween 80, Cremophor RH 40 and Poloxamer 407. Formula F1 prepared with Phosal® 53 MCT (300 mg), Tween 80 (50 mg), cholesterol (50 mg) and Silymarin (140 mg) showed the smallest particle size (2066 ± 164.87 nm) upon reconstitution in water, highest encapsulation efficiency (89.51 ± 0.43%), and fastest in vitro release compared to other formulas. Cytotoxicity of Silymarin, formula F1 and formula F1/blank was assessed using an MTT assay on MCF-7, HepG2 and HBF-4 cells. The cytotoxic effect of silymarin was enhanced by loading it on proliposomes. Conclusion: Silymarin was successfully formulated into proliposomes combining ethanol injection and spray drying methods. The cytotoxicity of silymarin was improved when loaded on proliposomes owing to the formula.

Introduction: In the present research, erythromycin estolate loaded in-situ gel was formulated and evaluated for blepharitis in order to improve its therapeutic efficacy, precorneal residence time of the system and to enhance the ocular bioavailability. Materials and Methods: The developed formulation was characterized by several parameters viz. FTIR, clarity, pH, gelation temperature, rheological studies, drug content, in vitro drug release studies, transcorneal permeation studies, bioadhesion studies, isotonicity and stability studies. Results: The optimized formulation exhibited non-fickian release diffusion with a sustained release of drug 82.76 ± 0.94% up to 8h and drug content 93.64%. Isotonicity revealed that the formulation was isotonic in nature and there was no shrinkage and busting of cells. Bioadhesion study was performed to check the adherence of the prepared in situ gel to the corneal surface for 4h. Ex vivo transcorneal permeation was observed to be significantly higher when compared with market eye drops. Histopathological studies were conducted to confirm the presence of normal ocular surface tissues by maintaining their morphological structures without causing damage to the tissues. The formulation was nonirritant as confirmed by the HET-CAM test. Stability studies and accelerated stability studies were conducted for 13 weeks and 26 weeks respectively and formulations were analyzed for the visual appearance, pH, viscosity, gelling capacity, drug content and in vitro drug release and results showed no change in the formulations. Conclusion: The formulation was therapeutically efficacious, sterile, stable and provided controlled release over a period of time. The developed system could be a viable alternative to conventional eye drops for treatment of various ocular diseases.

Objective: Andrographolide has potent anticancer and antimicrobial activity; however, its clinical application has been limited due to its poor water solubility as well as lack of appropriate formulation. The objective of this investigation was to formulate Self–Micro Emulsifying Drug Delivery System (SMEDDS) of andrographolide and explore its oral drug delivery aptitudes. Methods: Andrographolide SMEDDS was optimized by ternary phase approach and studied for various in vitro characteristics: Particle size, electron microscopy, polydispersity index, surface charge, dilution effect, pH stability, freeze-thaw effect, dissolution profile and stability studies. Further, antimicrobial and cytotoxic performance of andrographolide SMEDDS were evaluated in MCF–7 breast cancer cell lines and methicillin-resistant microorganisms, respectively. Results: An optimized SMEDDS formulation of andrographolide was successfully prepared and evaluated for its drug delivery potential. The solubility of andrographolide in the developed SMEDDS formulation was increased significantly, and the drug loading was enough for making this drug clinically applicable. The andrographolide SMEDDS formulation competitively inhibited the growth of microorganisms and showed enhanced anti–microbial activity against MRSA microorganisms. Conclusions: The SMEDDS strategy represents one of the best approaches to deliver andrographolide via oral route, while resolving its solubility limitations.

Objective: The purpose of the present study was to develop a novel elastic bilayer vesicle entrapped with Flurbiprofen (FLB) for transdermal use to avoid adverse effect associated with oral administration of the drug. Encapsulation of drug in vesicle prolongs the existence of the drug in the systemic circulation and thus enhances penetration into the target site and reduces toxicity. Method: Niosomes were prepared using surfactants (span 40 and span 60) and cholesterol in the molar ratio of 1:1, 2:1, 3:1 and 3:2. Vesicles prepared by thin film hydration method were characterized for morphology, vesicle size and zeta potential, thermal analysis and Entrapment Efficiency (EE). Results: Results revealed that the EE and size of niosomes were influenced by surfactant type and cholesterol ratio. F8 (span 60: cholesterol in 3:2) exhibited the highest encapsulation of FLB (76.77 ± 0.55) with vesicle size of 154 ± 2.96 nm and Polydispersity Index (PDI) of 0.09. The optimized formulation F8 was selected for incorporation into the gel. Niosomal gel was evaluated for homogeneity, pH, spreadability and in-vitro drug release. Conclusion: All the parameters of niosomal gel were found to be satisfactory and in-vitro release study revealed prolonged and complete release of entrapped FLB (93.23±0.65%) in comparison to FLB hydrogel (42.65±0.29%). The results suggested that niosomes may serve as promising vehicles for the transdermal delivery of FLB.

Objective: Ketoconazole is used in the treatment of superficial and systemic fungal infections. It acts by blocking the synthesis of ergosterol, an essential component of the fungal cell membrane. The purpose of this work was to formulate ketoconazole loaded nanostructured lipid carriers formulation for skin targeting to minimize the adverse side effects and to prolong release. Methods: The ketoconazole loaded nanostructured lipid carriers were optimized using 32 factorial design to evaluate the effects of process and formulation variables. The nanostructured lipid carriers were prepared by melt-dispersion ultra-sonication method. The formulations were finally incorporated into polymeric gels of Carbopol 940 for convenient application. The gels were evaluated comparatively with commercially available formulations of ketoconazole with respect to ex vivo skin permeation and deposition study on human cadaver skin. Results: Nanostructured lipid carriers showed average particle size, zeta potential, and percentage entrapment in the range of 125.8 ± 1.8 to 295.0 ± 3.8 nm, -13.2 ± 1.1 to -30.9 ± 2.2 mV, and 69.47 ± 2.8 to 95.49 ± 4.5, respectively. Thermal studies revealed no drug-excipient incompatibility and amorphization of ketoconazole. Ex vivo study of the gel exhibited prolonged drug release up to 12 h. In vitro drug deposition study showed that the gel formulation can avoid the systemic uptake, better accumulative uptake of the drug, and nonirritant to the skin compared to marketed formulation. Optimized formulation exhibited better antifungal activity when compared to ketoconazole loaded gel and marketed cream (Keto ® cream). Histolopathology results indicated no toxic effect on the skin. Conclusions: These results indicate that developed nanostructured lipid-carriers gel formulation represents a promising carrier for topical delivery of ketoconazole, having controlled drug release, and potential of skin targeting.

Background: We report the effectiveness of a targeted delivery system containing Meloxicam using polysaccharides for the treatment of colorectal cancer. We also propose a novel biorelevant dissolution method to overcome drawbacks of existing dissolution methodologies of polysaccharidebased systems. The proposed method includes a mixture of probiotics cultured under anaerobic conditions in the presence of prebiotic in the in vitro dissolution study to surrogate colonic conditions. Polysaccharide- based system can be simple, safe and effective drug delivery system to target drugs to colon. Methods: Press-coated tablets of Meloxicam were prepared by direct compression using various polysaccharides, such as xanthan gum, guar gum and pectin as coating polysaccharides. Developed tablets were evaluated for physical parameters, lag phase and in vitro drug release. Developed probioticsbased dissolution method was validated and explored for versatility using other polysaccharides. Results: Press-coated tablets of Meloxicam were successfully developed exhibiting targeted delivery to the colon using guar gum as coat and releasing more than 80% of drug in simulated colonic fluid. The developed probiotics based dissolution method may prove to be useful as a bio-relevant and discriminatory method. Conclusion: Developed Meloxicam tablets press-coated with guar gum can be taken orally for treatment or as an adjuvant therapy in colon cancer. Polymers used in this formulation are abundant, nontoxic, biodegradable and inexpensive which make this a a very promising approach for the treatment of different colonic diseases. The proposed biorelevant, animal sparing, probiotics based dissolution medium was found to be versatile to study drug release from other polysaccharide based formulations for colonic delivery.