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Topotecan (TPT) is a semi-synthetic, water-soluble derivative of camptothecin, which inhibits the action of topoisomerase I in the S-phase of the cell cycle leading to cell death. For the effective delivery of TPT to cancer cells, pH-sensitive sialic acid modified liposomes were developed. These liposomes were prepared by the thin-film hydration method using the active loading technique. Vesicle size, polydispersity index (PDI), zeta potential, and percentage entrapment efficiency were determined to be 167   ±   3.78   nm, 0.243, -8.39   mV, and 79.88   ±   1.67%, respectively. The pH-sensitive sialic acid (SA) conjugated liposomes enhanced the drug release at acidic pH 4 (92.33   ±   4.21%) as compared to physiological pH 7.4 (63.11   ±   4.51%). A Sulforhodamine B (SRB) cytotoxicity assay was performed in Murine sarcoma S180 cell lines and the GI 50 value of free TPT, Lipo, P-Lipo, SA-P-Lipo, and Adriamycin (ADR) were determined to be 10.07   ±   0.15, 27.33   ±   1.01, 28.76   ±   0.87, 15.7   ±   0.45, and 11.5   ±   0.21   µg/mL, respectively. Results obtained from the apoptosis study revealed that cell death by a combination of early apoptosis and apoptosis caused by SA-P-Lipo was ∼24 fold higher than the control. These results demonstrated that pH-sensitive sialic acid conjugated liposomes will be a potential formulation for improving the antitumor efficacy of TPT. However, further research is necessitated to expedite its applicability in clinical regimen in order to ascertain its safety and efficacy.

Introduction: Niosomes have recently grabbed attention as one of the best tools for various site-specific drug delivery systems, including ophthalmic drug delivery. Surfactants (nonionic; tweens and spans) of different HLB values and cholesterol are the fundamental components for these formulations. It is an alternative controlled ocular drug delivery system to liposomes to overcome the problems associated with sterilization, large-scale production, and stability. It also enhances the adhesion or retention ability of drug at the ocular site. Hydrophilic or lipophilic or amphoteric drugs can be easily encapsulated in niosomes. Besides, niosomes are a leading vesicular system compatible with most of the drugs for site-specific delivery., Areas Covered: This article reveals challenges and barriers for ocular drug delivery, various transporters and receptors present in the ocular region for the transportation of therapeutics as well as nutrients, and various method of preparations, loading methods and application potential of niosomes in ocular drug delivery., Expert Opinion: Niosomes, a vesicular system offers numerous advantages and applicability because of its good stability, non-immunogenicity, permeation potential, and controlled release ability etc. This drug delivery system has been efficiently used in the treatment of many ocular diseases.

Fungal keratitis (FK) is treated by topical natamycin (Nat) which is an effective antifungal agent. However, it has numerous therapeutic limitations i.e. toxicity, tolerance, need of frequent dosing and patient incompliance. The aim of the present study was to develop Nat loaded trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes (Muc-Cat-Nios) for prolonged and effective delivery to eyes. Niosomes were prepared using thin film hydration method and optimized using a Box-Behnken design (BBD) with the help of Design-Expert® Software. Three independent variables were considered: amount of Span 60 (X 1 ), amount of Cholesterol [Chol(X 2 )] and TMC concentration (X 3 ). The encapsulation efficiency (R1: EE%), vesicle size (R2: VS) and Zeta potential (R3: ZP) were selected as dependent variables or responses. The optimized Nios displayed spherical shape, 1034.14 nm vesicle size and 81.76% EE. Nat loaded niosomes were incubated with TMC to get mucoadhesive cationic vesicular system. Uncoated and TMC coated niosomes were characterized for mucoadhesive properties, in vitro drug release, rheological behaviour, and ex vivo permeation studies. Cationic Nios showed greater mucoadhesive potential that provided drug release for a long period of time. The promising outcomes suggest that natamycin delivery using cationic mucoadhesive niosomes could be employed for the effective treatment of fungal keratitis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: This investigation was aimed to explore the targeting potential of folate conjugated double liposomes (fDLs) bearing combination of synergistic drugs (Prednisolone and Methotrexate) for effective management of the rheumatoid arthritis (RA)., Methods: To overcome the drawbacks of monotherapy, a combination of prednisolone (PRD) (an anti-inflammatory agent) and methotrexate (MTX) (a disease modifying anti-rheumatoid agent, DMARDs) was chosen for dual targeting approach. fDLs were prepared in two steps i.e. development of inner liposomes (ILs) using thin film casting method followed by encapsulation of ILs within folate conjugated outer liposomes (double liposomes; fDLs). Developed liposomes were characterized for various physicochemical parameters and in vivo performance., Results: fDLs were prepared using FA-PEG-4000-NH-DSPE conjugate. These double liposomes were having 429.3 ± 3.6 nm in size with 0.109 PDI, 8.01 ± 0.3 mV zeta potential (ζ) and 66.7 ± 3.9% and 45.3 ± 1.7% entrapments of PRD and MTX, respectively. After 24 h, the concentrations of PRD in blood were observed to be 8.66 ± 3.11 (ILs) and 15.13 ± 0.81% (DLs) while concentration of MTX were found to be 10.89 ± 0.69 and 2.34 ± 3.15% when given as ILs and fDLs, respectively. The concentration of both drugs in inflamed joint was observed to be higher than that in the non-inflamed joints., Conclusions: The folate conjugated double liposomes possess superior targeting efficiency than conjugated and unconjugated single liposomes.

Background: Curcumin has been extensively employed in the treatment of several diseases in traditional medicine, including cancer. The main obstacles that avert its approval as a therapeutic moiety are its low aqueous solubility and low in vivo bioavailability. Liposomes have been recognized as effective carrier systems owing to their ability to solubilize hydrophobic molecules and to change their pharmacokinetic attributes. This study was intended at developing Eudragit S 100 coated alginate beads bearing curcumin loaded liposomes for colonic delivery. Methods: The liposomes were prepared by the film casting method. The optimization of various formulation and process variables was done by Box-Behnken design using Design-Expert® Software. Three variables i.e.HSPC:Chol molar ratio (X1), curcumin concentration (X2), and sonication time (X3) were selected as independent variables and entrapment efficiency of curcumin, polydispersity index, and vesicle size were selected as dependent variables. Results: The optimized liposomes had an average particle size of 109. 8 ± 1.4 nm, polydispersity index 0.218 ± 1.2, zeta potential +19.30 ± 2.46 mV, and with entrapment efficiency 70.16 ± 1.6 %. These liposomes were entrapped in eudragit coated beads and these beads were characterized for their size, swelling index and in vitro drug release. The in vitro drug release depicted that no release was observed till 6 hrs and a sustained and significant drug release was noted after 6.5 hr. Conclusion: The stability studies indicated that liposomes were stable at 4°C depicting little aggregation of the vesicles. The research suggested that curcumin-loaded liposomes bearing eudragit coated calcium alginate beads can be effectively used for colonic delivery. [ABSTRACT FROM AUTHOR]

Over the past few decades, applications of ultrasound (US) in drug delivery have been documented widely for local and site-specific release of bioactives in a controlled manner, after acceptable use in mild physical therapy for tendinitis and bursitis, and for high-energy applications in fibroid ablation, cataract removal, bone fracture healing, etc. US is a non-invasive, efficient, targetable and controllable technique. Drug delivery can be enhanced by applying directed US in terms of targeting and intracellular uptake. US cannot only provide local hyperthermia but can also enhance local extravasations and permeability of the cell membrane for delivery of cell-impermeable and poorly permeable drugs. It is also found to increase the anticancer efficacy of drug against solid tumors by facilitating uniform drug delivery throughout the tumor mass. This review summarizes the mechanism of US; various drug delivery systems like microbubbles, liposomes, and micelles; and biological manifestations employed for improving treatment of cancer, i.e., hyperthermia and enhanced extravasation. Safety issues are also discussed for better therapeutic outcomes of US-assisted drug delivery to tumors. This review can be a beneficial asset to the scientists looking at non-invasive techniques (externally guided) for improving the anticancer potential of drug delivery systems. [ABSTRACT FROM AUTHOR]