Functionalized nanoscale oil bodies for targeted delivery of a hydrophobic drug

Effective formulations of hydrophobic drugs for cancer therapies are challenging. To address this issue, we have sought to nanoscale artificial oil bodies (NOBs) as an alternative. NOBs are lipid-based particles which consist of a central oil space surrounded by a monolayer of oleosin (Ole)-embedded phospholipids (PLs). Ole was first fused with the anti-HER2/neu affibody (Ole-ZH2), and the resulting hybrid protein was overproduced in Escherichia coli. ZH2-displayed NOBs were then assembled by sonicating the mixture containing plant oil, PLs, and isolated Ole-ZH2 in one step. To illustrate their usefulness, functionalized NOBs were employed to encapsulate a hydrophobic anticancer drug, Camptothecin (CPT). As a result, these CPT-loaded NOBs remained stable in serum and the release of CPT at the non-permissive condition exhibited a sustained and prolonged profile. Moreover, plain NOBs were biocompatible whereas CPT-loaded NOBs exerted a strong cytotoxic effect on HER2/neu-positive cells in vitro. Administration of xenograft nude mice with CPT-loaded NOBs also led to the regression of solid tumors in an effective way. Overall, the result indicates the potential of NOBs for targeted delivery of hydrophobic drugs.     

Pluronic F127 nanomicelles engineered with nuclear localized functionality for targeted drug delivery

PKKKRKV (Pro-Lys-Lys-Lys-Arg-Lys-Val, PV7), a seven amino acid peptide, has emerged as one of the primary nuclear localization signals that can be targeted into cell nucleus via the nuclear import machinery. Taking advantage of chemical diversity and biological activities of this short peptide sequence, in this study, Pluronic F127 nanomicelles engineered with nuclear localized functionality were successfully developed for intracellular drug delivery. These nanomicelles with the size ~ 100 nm were self-assembled from F127 polymer that was flanked with two PV7 sequences at its both terminal ends. Hydrophobic anticancer drug doxorubicin (DOX) with inherent fluorescence was chosen as the model drug, which was found to be efficiently encapsulated into nanomicelles with the encapsulation efficiency at 72.68%. In comparison with the non-functionalized namomicelles, the microscopic observation reveals that PV7 functionalized nanomicelles display a higher cellular uptake, especially into the nucleus of HepG2 cells, due to the nuclear localization signal effects. Both cytotoxicity and apoptosis studies show that the DOX-loaded nanomicelles were more potent than drug nanomicelles without nuclear targeting functionality. It was thus concluded that PV7 functionalized nanomicelles could be a potentially alternative vehicle for nuclear targeting drug delivery.     

Bioeliminable nanohydrogels for drug delivery

One of the most significant obstacles for systematic delivery of nanopayloads is the foreign particle clearance by the mononuclear phagocyte system (MPS). The majority of biocompatible nanopayloads with charged groups on their surface cannot fully evade the clearance by MPS during systemic circulation. For safe and effective targeted nanodrug delivery in vivo, we describe a novel approach for evading the macrophage clearance. We demonstrate that neutral and hydrophilic materials can effectively evade the macrophage uptake and also quickly degrade into bioeliminable fragments. We show that there is no opsonization effect and no toxic effect on living cells. In addition, the payloads are stable in an aqueous environment, and they can release drugs in a cellular environment. These results suggest that the unique properties of this kind of payloads may make them useful for designing new drug delivery systems.     

Hydroxypatite-polysaccharide granules for drug delivery

The formation of hydroxyapatite by co-precipitation from sodium alginate and sodium carboxymethylcellulose aqueous solutions with the use of dibasic calcium phosphate dihydrate and calcium hydroxide as starting reagents is studied. A technique to prepare the hydroxyapatite/polysaccharide (micro)granules is developed. An introduction of an antimicrobial Biocide 1 agent in proper amount into the granules is provided, and the behavior of the granules is evaluated.     

Nanoparticles for intracellular-targeted drug delivery

Nanoparticles (NPs) are very promising for the intracellular delivery of anticancer and immunomodulatory drugs, stem cell differentiation biomolecules and cell activity modulators. Although initial studies in the area of intracellular drug delivery have been performed in the delivery of DNA, there is an increasing interest in the use of other molecules to modulate cell activity. Herein, we review the latest advances in the intracellular-targeted delivery of short interference RNA, proteins and small molecules using NPs. In most cases, the drugs act at different cellular organelles and therefore the drug-containing NPs should be directed to precise locations within the cell. This will lead to the desired magnitude and duration of the drug effects. The spatial control in the intracellular delivery might open new avenues to modulate cell activity while avoiding side-effects.     

Nanocarrier-based topical drug delivery for an antifungal drug

Objective: The conventional liposomal amphotericin B causes many unwanted side effects like blood disorder, nephrotoxicity, dose-dependent side effects, highly variable oral absorption and formulation-related instability. The objective of the present investigation was to develop cost-effective nanoemulsion as nanocarreir for enhanced and sustained delivery of amphotericin B into the skin.

Methods and characterizations: Different oil-in-water nanoemulsions were developed by varying the composition of hydrophilic (Tween® 80) surfactants and co-surfactant by the spontaneous titration method. The developed formulation were characterized, optimized, evaluated and compared for the skin permeation with commercial formulation (fungisome 0.01% w/w). Optimized formulations loaded with amphotericin B were screened using varied concentrations of surfactants and co-surfactants as decided by the ternary phase diagram.

Results and discussion: The maximum % transmittance obtained were 96.9?±?1.0%, 95.9?±?3.0% and 93.7?±?1.2% for the optimized formulations F-I, F-III and F-VI, respectively. These optimized nanoemulsions were subjected to thermodynamic stability study to get the most stable nanoemulsions (F-I). The results of the particle size and zeta potential value were found to be 67.32?±?0.8 nm and –3.7?±?1.2?mV for the final optimized nanoemulsion F-I supporting transparency and stable nanoemulsion for better skin permeation. The steady state transdermal flux for the formulations was observed between 5.89?±?2.06 and 18.02?±?4.3?µg/cm²/h whereas the maximum enhancement ratio were found 1.85- and 3.0-fold higher than fungisome and drug solution, respectively, for F-I. The results of the skin deposition study suggests that 231.37?±?3.6?µg/cm² drug deposited from optimized nanoemulsion F-I and 2.11-fold higher enhancement ratio as compared to fungisome. Optimized surfactants and co-surfactant combination-mediated transport of the drug through the skin was also tried and the results were shown to have facilitated drug permeation and skin perturbation (SEM).

Conclusion: The combined results suggested that amphotericin B nanoemulsion could be a better option for localized topical drug delivery and have greater potential as an effective, efficient and safe approach.     

Porous ceramic bodies for drug delivery

An approach to the production of ceramic drug delivery devices is proposed. Two examples of possible ceramics are dealt with: hydroxyapatite weakly modifiable by living tissue and the bioinert alumina. The possibility to control the formed porosity was taken into consideration for both materials. The ratio between the acquired porosity and the quantity and quality of the agents inducing porosity is also described and discussed. A test on the role of porosity was performed on the obtained porous ceramic bodies and a study was made on the release of a substance with pharmacological activity from previously impregnated porous ceramic bodies. This paper is preliminary to a planned work targeted to the preparation of ceramic drug delivery systems.     

Novel drug delivery system for captopril

Abstract

It is known that drug substances showing no difference in absorbance along the whole gastro-intestinal (GI) tract are suitable for SR-formulations with an extended release characteristic. However, a decrease in bioavailability from proximal to distal parts of the gut may be suited for a limited retard effect. In this investigation, attempts have been made to design a suitable delivery system for captopril which is poorly bio-available from the alkaline regions of the GI-tract. The principles of ‘Bioadhesion’ as well as ‘Gastric Floating Systems’ are utilized in this study.     

Water-soluble soft nano-colloid for drug delivery

Photodynamic therapy (PDT) has been proved to be highly effective in the treatment of different types of cancer. A novel nano-colloid based drug carrier for PDT of elsinochrome A (EA), a hydrophobic photosensitizer, was prepared using single 3-aminopropyltriethoxysilane (APTES) which is traditionally only used as surface modification reagent. The resulting nano-colloid immobilized photosensitizers provide good water solubility and photostability. In addition, EANC preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. Moreover, significant damage to calf thymus DNA was observed upon irradiation with light. Thus, the potential of using nano-colloid as drug carriers for photodynamic therapy has been demonstrated.     

Novel drug delivery system for captopril

It is known that drug substances showing no difference in absorbance along the whole gastro-intestinal (GI) tract are suitable for SR-formulations with an extended release characteristic. However, a decrease in bioavailability from proximal to distal parts of the gut may be suited for a limited retard effect. In this investigation, attempts have been made to design a suitable delivery system for captopril which is poorly bio-available from the alkaline regions of the GI-tract. The principles of 'Bioadhesion' as well as 'Gastric Floating Systems' are utilized in this study.     

Permeation enhancers for transdermal drug delivery

The transdermal route has been recognized as one of the highly potential routes of systemic drug delivery and provides the advantage of avoidance of the first-pass effect, ease of use and withdrawal (in case of side effects), and better patient compliance. However, the major limitation of this route is the difficulty of permeation of drug through the skin. Studies have been carried out to find safe and suitable permeation enhancers to promote the percutaneous absorption of a number of drugs. The present review includes the classification of permeation enhancers and their mechanism of action; thus, it will help in the selection of a suitable enhancer(s) for improving the transdermal permeation of poorly absorbed drugs.     

PVA engineered microcapsules for targeted delivery of camptothecin to HeLa cells

Capsular microvectors are an important tool in the recent research field of nanomedicine to address a drug cargo for the therapeutic treatment of several pathologies. In this study we describe how the product of the conjugation of the polysaccharide chitosan with folate can be used as a coating of poly (vinyl alcohol), PVA, based microcapsules for an efficient targeting of HeLa cells. The influence of the coating on the bioadhesive properties of the vector and on its cargo capacity was also considered using camptothecin as an anticancer drug model. The coating strategy was finalized to exploit the good chemical versatility of PVA, used to form the shell of the vector. This study is a follow up of an investigation activity aiming to show the potentialities of PVA-shelled microcapsules or microbubbles as injectable microdevices supporting a theranostic approach for different types of tumour.     

Strong dual-crosslinked hydrogels for ultrasound-triggered drug delivery

Nano Research - Hydrogels that can respond to dynamic forces either from endogenous biological activities or from external mechanical stimuli show great promise as novel drug delivery systems...     

Calcium pectinate capsules for colon-specific drug delivery

The calcium pectinate (CaP) capsule, a novel, colon-specific delivery system, was designed and developed using 5-fluorouracil (5-FU) as a model drug. Technically, CaP capsules were prepared by dipping a glass or stainless steel rod successively into pectin and calcium chloride solutions, followed by subsequent air-drying and coating. In vitro studies showed that the release of 5-FU from CaP capsules markedly increased in the presence of rat cecal contents, and the release characteristic was mainly associated with some capsule parameters such as calcium content, shell thickness, and coat amount. Gamma scintigraphic studies demonstrated that CaP capsules could pass through the stomach and small intestine intact and could release drug in colon. The 5-FU releasing characteristics acquired both from in vitro biomimic dissolution experiments and from healthy volunteers indicated that the newly developed CaP capsule possessed the ideal colon-specific drug delivery characteristic.