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Breast carcinoma (BC) is one of the most frequent causes of cancer-related death among women, which is due to the poor response to conventional therapy. There are several complications associated with monotherapy for cancer, such as cytotoxicity to normal cells, multidrug resistance (MDR), side effects, and limited applications. To overcome these challenges, a combination of chemotherapy and immunotherapy (monoclonal antibodies, anticancer vaccines, checkpoint inhibitors, and cytokines) has been introduced. Drug delivery systems (DDSs) based on nanotechnology have more applications in BC treatment owing to their controlled and targeted drug release with lower toxicity and reduced adverse drug effects. Several nanocarriers, such as liposomes, nanoparticles, dendrimers, and micelles, have been used for the effective delivery of drugs.This article presents opportunities and challenges in BC treatment, the rationale for cancer immunotherapy, and several combinational approaches with their applications for BC treatment.Nanotechnology can be used for the early prognosis and cure of BC. Several novel and targeted DDSs have been developed to enhance the efficacy of anticancer drugs. This article aims to understand new strategies for the treatment of BC and the appropriate design of nanocarriers used as a combinational DDS.

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...

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 (X1), amount of Cholesterol [Chol(X2)] and TMC concentration (X3). 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.

Gellan gum (GG) is a bacterial exopolysaccharide obtained commercially from Sphingomonas paucimobilis. Two chemical forms of GG exist, i.e. native/acylated and deacylated. Ionotropic/ionic gelation is a promising tool in the development of biocompatible novel drug delivery systems. GG is a naturally occurring polysaccharide that bears the potential to encapsulate a large number of micro- and macro-therapeutic molecules via different carrier systems such as microspheres, hydrogels, beads and microparticles. By the achievements of polymer chemistry, development of intelligent and the strategic encapsulation techniques helps the natural polysaccharide to use in numerous drug delivery. The usage of expensive and toxic organic solvents in the microencapsulation process has been significantly minimized by the progress of ionotropic gelation method. Ionically gelled GG delivers great prospects for designing new drug delivery systems, thus encompassing the frontier of future pharmaceutical development.

Ultrasound stimulated drug delivery (USDD) is a unique strategy for drug delivery an essential research area for chemotherapy. Ultrasound (US) technique is an effective, noninvasive, targetable, and controllable technique where sound waves are utilized for cancer treatment. US can directly enhance the effective therapeutic concentration at target site, as it usually increases the penetrability of cell membrane for the poorly permeable drug and causes local hyperthermia. Recent research studies have explored polymer technology for triggered drug/gene delivery using external stimuli such as ultrasound, electromagnetic and laser induction. Several biodegradable polymers possess US-responsive characteristics which could be utilized in cancer therapy via hyperthermia and sonoporation using High Intensity Focused Ultrasound (HIFU). The nanocarrier with US has display a great potential in diagnostic and therapeutic application in cancer. Exploited USDD systems include nanobubbles, nanodroplets, micelles, liposomes, microbubbles and nanoparticles etc. This chapter encompasses a detailed account of basic, recent advances and emerging application of USDD systems in cancer chemotherapy.

The present research was aimed to develop thiolated polyacrylic acid (TPA) based microspheres (MSPs) containing famotidine (FX) and clarithromycin (CLX).TPA was synthesised from polyacrylic acid and l-cysteine in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDAC). The prepared TPA was characterised using FT-IR (Fourier transform-infra red),The average particle size and zeta potential of optimised formulation was found to be 25.2 ± 1.87 μm and -26.68 mV, respectively. The entrapment efficiency of the optimised formulation was obtained 67.20% for FX and 70.20% for CLX. The developed microspheres were swelled only in 4 h from 0.5 to 0.9. TheThe prepared TPA based mucoadhesive microspheres can be utilised as carriers for the treatment of peptic ulcer caused by

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.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.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 a corneal infection caused by different fungal species. It is treated by the topical application of natamycin (NAT). Nevertheless, this approach faces many limitations like toxic effects, frequent dosing, resistance, and patient discomfort. The present research reports the development of trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes by a modified thin-film hydration method. TMC was synthesized using a one-step carbodiimide method and characterized by 1H-NMR and degree of quaternization (53.74 ± 1.06%). NAT, cholesterol (CHOL), span 60 (Sp60), and dicetyl phosphate (DCP) were used to prepare niosomes which were incubated with TMC to obtain mucoadhesive cationic NAT loaded niosomes (MCNNs). MCNNs showed a spherical shape with 1031.12 ± 14.18 nm size (PDI below 0.3) and 80.23 ± 5.28% entrapment efficiency. In vitro drug release studies showed gradual drug release from TMC coated niosomes as compared to the uncoated niosomes. MIC assay and disk diffusion assay revealed promising in vitro antifungal potential of MCNNs similar to the marketed formulation. For investigating in vivo performance, ocular retention and pharmacokinetics, ocular irritation, and ulcer healing studies were performed using the rabbit model. Mucoadhesive property and prolonged local drug release improved the safety and efficacy of NAT, suggesting that the developed niosomes could be an emerging system for effective treatment of fungal keratitis.

Chemotherapy of cancer is still considered a complex phenomenon given that single chemotherapeutic agents cannot be administered for a long period of time because of the development of drug resistance and severe side effects. Nanodrug delivery systems (NDDSs) such as nanoparticles and liposomes are being investigated to enhance the safety and efficacy of anticancer agents. NDDS-based delivery of a single agent is not found to be effective in long-term anticancer therapy. Codelivery of more than one anticancer agent using liposomes shows great potential since it exhibits simultaneous synergistic therapeutic manifestations at the tumor site and enhances therapeutic efficacy in terms of the low-dose requirement of each agent and diminished side effects. Liposomes are lipid vesicles arranged in concentric bilayers with an aqueous core; they are versatile nanocarriers that accommodate the diverse nature of anticancer drugs (both hydrophobic and hydrophilic) at the same time. They offer a number of advantages for combinatorial drug delivery in terms of increased blood circulation, selective accumulation at tumor tissues, and stimuli responsiveness. Various combination of drugs such as paclitaxel (PTX) and topotecan, sunitinib and irinotecan, and combretastin A-4 and doxorubicin have been reported for cancer chemotherapy using liposomes. This review focuses on recent scenarios of combinatorial drug delivery using liposomes for better chemotherapeutic outcomes. This assemblage can be of great importance to researchers looking for advances in novel drug delivery approaches for better cancer treatment.

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

Colorectal cancer (CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer cells. Sonic Hedgehog (SHH), Wnt wingless-type mouse mammary tumor virus/β-catenin, transforming growth factor-β/SMAD, epidermal growth factor receptor and Notch are the main signaling pathways involved in the progression of CRC. Targeted therapies necessitate information regarding the particular aberrant pathways. Advancements in gene therapies have resulted in the recognition of novel therapeutic targets related with these signal-transduction cascades. CRC is a step-wise process where mutations occur over the time and activation of oncogenes and deactivation of tissue suppressor genes takes place. Genetic changes which are responsible for the induction of carcinogenesis include loss of heterozygosity in tumor suppressor genes such as adenomatous polyposis coli, mutation or deletion of genes like p53 and K-ras. Therefore, many gene-therapy approaches like gene correction, virus-directed enzyme-prodrug therapy, immunogenetic manipulation and virotherapy are currently being explored. Development of novel strategies for the safe and effective delivery of drugs to the cancerous site is the need of the hour. This editorial accentuates different novel strategies with emphasis on gene therapy and immunotherapy for the management of CRC.

Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors. They exist in three isoforms (PPAR-α, PPAR-β/δ, and PPAR-Υ) in humans, but mainly PPAR-Υ, and they are expressed in retinal epithelial pigment. PPARs are involved in mediating numerous pathological implications in eye such as diabetic retinopathy (DR), choroidal neovascularization (CNV), glaucoma, diabetic macular edema, and other retinal diseases. Peroxisome proliferator-activated receptors are key players in various biological pathways like lipid degeneration, immune regulation, and reactive oxygen species regulation, regulation of vascular endothelial growth factor, matrixmetalloproteinase-9, and docosahexaenoic acid pathway. Based on evidence from clinical investigations, the drugs meant for PPARs could be promising candidates for intraocular therapy. Anti-VEGF therapy, including bevacizumab, ranibizumab, and aptamers (pegaptanib), has been approved for wet age-related macular degeneration (ARMD). Recently, researchers have explored the role of PPAR-γ in ocular pathophysiological processes and PPAR-γ agonists as novel adjuvants in the treatment of eye diseases. PPAR-γ exhibits potential benefits to improve or prevent various vision-threatening eye diseases such as age-related macular degeneration (ARMD), diabetic retinopathy (DR), keratitis, and optic neuropathy. However, PPAR-γ presents challenges and offers opportunities for ocular scientists to bring better outcomes.

Liposomes are sphere-shaped vesicles consisting of one or more phospholipid bilayers. The liposomal drug delivery systems were utilized for delivery of compounds for different diseases. These systems improve the stability as well as cellular uptake of drugs. Site-specific delivery to the target site reduced the site effects. This chapter summarizes the recent advances in liposomal drug delivery systems (i) therapeutic applications-based chemotherapy; (ii) chemotherapy in combination to gene therapy and immunotherapy; (iii) theranostic applications for precise detection and simultaneous treatment of critical diseases and heavy metal toxicity; (iv) stimuli-triggered liposomes. This chapter gives a detailed account on aforementioned applications which might be beneficial to pharmaceutical scientists and industries to develop safe and effective liposomal systems.

Colorectal cancer (CRC) is the third most common cancer existing across the globe. It begins with the formation of polyps leading to the development of metastasis, especially in advanced stage patients, who necessitate intensive chemotherapy that usually results in a poor response and high morbidity owing to multidrug resistance and severe untoward effects to the non-cancerous cells. Advancements in the targeted drug delivery permit the targeting of tumor cells without affecting the non-tumor cells. Various nanocarriers such as liposomes, polymeric nanoparticles, carbon nanotubes, micelles, and nanogels, etc. are being developed and explored for effective delivery of cytotoxic drugs to the target site thereby enhancing the drug distribution and bioavailability, simultaneously subduing the side effects. Moreover, immunotherapy for CRC is being explored for last few decades. Few clinical trials have even potentially benefited patients suffering from CRC, still immunotherapy persists merely an experimental alternative. Assessment of the ongoing and completed trials is to be warranted for effective treatment of CRC. Scientists are paying efforts to develop novel carrier systems that may enhance the targeting potential of low therapeutic index chemo- and immune-therapeutics. Several preclinical studies have revealed the superior efficacy of nanotherapy in CRC as compared to conventional approaches. Clinical trials are being recruited to ascertain the safety and efficacy of CRC therapies. The present review discourses in a nutshell the molecular interventions including the genetics, signaling pathways involved in CRC, and advances in various strategies explored for the treatment of CRC with a special emphasis on nanocarriers based drug targeting.

Prostate cancer (PCa) is a worldwide issue, with a rapid increase in its occurrence and mortality. Over the years, various strategies have been implemented to overcome the hurdles that exist in the treatment of PCa. Consistently, there is a change in opinion about the methodologies in clinical trial that have engrossed towards the treatment of PCa. Currently, there is a need to resolve these newly recognized challenges by developing newer rational targeting systems. The ongoing clinical protocol for the therapy using different targeting systems is undertaken followed by local targeting to cancer site. A number of new drug targeting systems like liposomes, nanoemulsions, magnetic nanoparticles (MNPs), solid lipid nanoparticles, drug-peptide conjugate systems, drug-antibody conjugate systems, epigenetic and gene therapy approaches, and therapeutic aptamers are being developed to suit this protocol. Recent advancements in the treatment of PCa with various nanocarriers have been reported with respect to newly identified biological barriers and intended to solve the contexts. This review encompasses the input of nanotechnology in particular targeting of PCa which might escape the lifethreatening side effects and potentially contribute to bring fruitful clinical outcomes.

Polysaccharides are widely available, inexpensive and versatile polymer having good stability, safety, low biotoxicity, hydrophilicity, gelling ability, flexibility for chemical modification and biodegradability, which offer a vista of drug delivery applications. There are number polysaccharides like chitosan, chondroitin sulfate, dextrans, cyclodextrins, guar gum, pectin, inulin, etc., which have been exploited for colon-specific delivery. This chapter summarizes various polysaccharides and approaches based on microflora and pH for stimuli-responsive drug delivery for colon targeting with special emphasis on drug delivery systems, such as microspheres, nanoparticles, hydrogels, matrices, and beads.

Natural polymers have been used in the formulation of novel drug delivery systems because of their ideal properties such as biodegradability, biocompatibility, and ease of availability. Locust bean gum (LBG) is a natural polymer, which has been used as an excipient in the conventional dosage forms because of its gelling and thickening properties. LBG is a nonstarch polysaccharide made up of galactose and mannose moieties and thus, it is known as galactomannan. LBG depicts synergistic effects with several other polysaccharides such as Κ-carrageenan and xanthan gum. It is utilized in the development of several drug delivery systems such as tablets, capsules, beads, microspheres, gel, and polymeric films. LBG-based preparations exhibit a sustained release pattern, and LBG also imparts mucoadhesion in few formulations. This chapter deals with different applications of LBG in various types of drug delivery systems.

Liposomes are biodegradable and biocompatible lipid bilayer vesicles which are widely exploited as preferred carriers for smart delivery of both hydrophobic as well as hydrophilic bioactives. Structural fabrication of liposomes for ligand anchoring, long-circulation and stimuli-responsiveness are advancing features to meet the needs of clinical and industrial demands. Recent studies report newer developments in multipronged liposomes for synchronized theranostic manifestations in cancer treatment. This review gives an insight to advances in ligand targeted liposomes (like folate, mannose, transferrin, hyaluronic acid, antibody, aptamer, and peptide, etc.), stimuli-triggered liposomes (stimuli such as pH, temperature, and hypoxia, etc.) and liposomes mediated autophagy modulation, and theranostic liposomes for the diagnosis and treatment of cancer. It also includes patents, clinical studies and marketed liposomal products. This assemblage of advances would be of great interest to budding scientists and pharmaceutical companies engaged in the development of liposomes.

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). 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. 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. The folate conjugated double liposomes possess superior targeting efficiency than conjugated and unconjugated single liposomes.

Numerous applications of colon-specific drug delivery have been found in a wide array of diseases like irritable bowel syndrome (IBS), inflammatory bowel diseases (ulcerative colitis and Crohn's disease), colorectal cancer, and diverticulitis. Drug delivery to the colon has different anatomic and pathophysiological barriers. In recent advancements, these barriers were overcome by using biodegradable polymeric nanoconstructs, which are exhibiting minimal systemic adverse effects. Various polymeric nanoconstructs (PNCs) such as nanoparticles, micelles, and dendrimers have been exploited for effective targeting to pathological sites of colon. PNCs on oral administration not only protect the bioactive from physicochemical degradation but also prevent premature leakage in the upper parts of gastrointestinal tract. The chapter summarizes various PNCs-based approaches for colon-specific drug delivery.

Topotecan (TPT), a potent anticancer camptothecin analog, is well described for the treatment of ovarian cancer, but has also anticancer activity against small-cell and non-small-cell lung cancer, breast cancer, and acute leukemia. Various nanocarriers, including liposomes, have been exploited for targeted delivery of TPT. However, there are a number of challenges with TPT delivery using TPT liposomes (TLs), such as low encapsulation efficiency, physiological pH labile E ring (hydrolysis), accelerated blood clearance, multidrug resistance, and cancer metastases. This review discusses these problems and the means to overcome them, including modification of TLs using zwitterionic poly(carboxybetaine), prolongation in dosing interval (long-term therapy), and modified liposomal encapsulation techniques including active loading methods. We also explore engineered TLs (surface and integral modifications) such as PEGylated TLs, ligand-anchored TLs, and stimuli-sensitive TLs. Further, potential applications, manifestations at the molecular level, patents granted, and preclinical and clinical outlook for TLs are discussed.