Madhu Gupta

Dual Targeted Polymeric Nanoparticles Based on Tumor Endothelium and Tumor Cells for Enhanced Antitumor Drug Delivery

Some specific types of tumor cells and tumor endothelial cells represented CD13 proteins and act as receptors for Asn-Gly-Arg (NGR) motifs containing peptide. These CD13 receptors can be specifically recognized and bind through the specific sequence of cyclic NGR (cNGR) peptide and presented more affinity and specificity toward them. The cNGR peptide was conjugated to the poly(ethylene glycol) (PEG) terminal end in the poly(lactic-co-glycolic) acid PLGA-PEG block copolymer. Then, the ligand conjugated nanoparticles (cNGR-DNB-NPs) encapsulating docetaxel (DTX) were synthesized from preformed block copolymer by the emulsion/solvent evaporation method and characterized for different parameters. The various studies such as in vitro cytotoxicity, cell apoptosis, and cell cycle analysis presented the enhanced therapeutic potential of cNGR-DNB-NPs. The higher cellular uptake was also found in cNGR peptide anchored NPs into HUVEC and HT-1080 cells. However, free cNGR could inhibit receptor mediated intracellular uptake of NPs into both types of cells at 37 and 4 °C temperatures, revealing the involvement of receptor-mediated endocytosis. The in vivo biodistribution and antitumor efficacy studies indicated that targeted NPs have a higher therapeutic efficacy through targeting the tumor-specific site. Therefore, the study exhibited that cNGR-functionalized PEG-PLGA-NPs could be a promising approach for therapeutic applications to efficient antitumor drug delivery.

Nanocarrier-based topical drug delivery for the treatment of skin diseases

Introduction: Skin disorders will continue to cause complications in patients. At present, there is an expansion of research into dermatologic treatment due to a critical need for new treatment options to treat skin diseases. Areas covered: The skin itself provides a natural barrier against particle penetration for topical delivery. However, it also offers a potential approach for the delivery of therapeutics, especially in diseased skin and via the openings of hair follicles. Recent innovation might be achieved in the field of dermatological treatment with improvement in the dermal localization of bioactives into the affected skin region, via novel nanocarriers that deliver the drugs directly to the target cells. After application, these nanocarriers can penetrate through the stratum corneum into viable skin and accumulate at the target site. However, noteworthy uptake does occur after damage and in certain diseased skin. Expert opinion: Skin-targeted topical delivery by means of nanosystems, in order to produce sustained release and maintain a localized effect, will result in an effective treatment of various life-threatening dermatological conditions. In addition, research continues into the interactions between novel particles, skin and skin lipid, and the influence of particle composition on drug distribution within the skin strata.

Development, characterization and in vivo assessment of effective lipidic nanoparticles for dermal delivery of fluconazole against cutaneous candidiasis.

The nanoparticulate carrier systems as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have gained interest for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Therefore in this study, SLNs and NLCs loaded fluconazole (FLZ) were prepared by solvent diffusion method in an aqueous system and characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that SLNs and NLCs represent the respective mean particle sizes of approx. 178 and 134 nm with encapsulation efficiency of 75.7±4.94% and 81.4±3.89%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of NLCs formulation. The in vivo cumulative amount of FLZ retention from NLCs was more than 5-fold that of the plain solution, while it was 3.3-fold more in the case of an equivalent-dose application in the form of SLNs at 12h after administration. The antifungal study also confirmed the maximum therapeutic efficacy of NLCs, as the lowest number of cfu/ml was recorded. It can be concluded from this study that NLCs provide a good skin targeting effect and may be a promising carrier for topical delivery of FLZ offering the sustained release and maintain the localized effect, resulting in an effective treatment of a life-threatening cutaneous fungal infection.

Development and characterization of effective topical liposomal system for localized treatment of cutaneous candidiasis

The localized delivery of fluconazole (FLZ) by conventional therapy is a major impediment in achieving its therapeutic efficacy against skin infections, such as cutaneous candidiasis. Therefore, the present study was aimed to develop FLZ-loaded vesicular construct(s), such as liposomes and niosomes, incorporated into carbopol gel (1%; w/w) for sustained, localized application. The liposomes and niosomes were prepared by the lipid/nonionic surfactant-based dry-film hydration method and were characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that the size of liposomes and niosomes was found to be 0.348 ± 0.054 and 0.326 ± 0.033 μm with encapsulation efficiency of 31.8 ± 1.36 and 27.6 ± 1.08%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments showed significantly higher accumulation of drug in the case of liposomal gel. The in vivo localization studies in viable skin showed that liposomal gel could produce 14.2-fold higher drug accumulation, compared with plain gel, while it was 3.3-fold more in the case of an equivalent-dose application in the form of niosomal gel. The antifungal study also confirmed the maximum therapeutic efficacy of liposomal gel, as the lowest number of cfu/mL was recorded following liposomal FLZ application. The studies signify the potential of liposomal gel for topical delivery of FLZ with increased accumulation of drug in various strata of skin vis-a-vis through sustained release of drug could maintain the localized effect, resulting in an effective treatment of a life-threatening cutaneous fungal infection.

Is nanotechnology a boon for oral drug delivery

The oral route for drug delivery is regarded as the optimal route for achieving therapeutic benefits owing to increased patient compliance. Despite phenomenal advances in injectable, transdermal, nasal and other routes of administration, the reality is that oral drug delivery remains well ahead of the pack as the preferred delivery route. Nanocarriers can overcome the major challenges associated with this route of administration: mainly poor solubility, stability and biocompatibility of drugs. This review focuses on the potential of various polymeric drug delivery systems in oral administration, their pharmacokinetics, in vitro and in vivo models, toxicity and regulatory aspects.

Recent advances in mucosal delivery of vaccines: role of mucoadhesive/biodegradable polymeric carriers

Importance of the field: The mucosal delivery of vaccines provides the basis for induction of humoral, cellular and mucosal immune responses against infectious diseases. The delivery of antigens to and through mucosal barriers always remains challenging due to adverse physiological conditions (pH and enzymes) and biological barriers created by tight epithelial junctions restricting transportation of macromolecules. Mucoadhesive and biodegradable polymers offer numerous advantages in therapeutic delivery of proteins/antigens particularly through the mucosal route by protecting antigens from degradation, increasing concentration of antigen in the vicinity of mucosal tissue for better absorption, extending their residence time in the body and/or targeting them to sites of antigen uptake. Furthermore, antigen can be delivered more effectively to the antigen presenting cells by anchoring the ligand having affinity on the surface of carrier for the receptors present on the mucosal epithelial cells. Areas covered in this review: The present review covers various polymeric carriers, which allow the possibility of modification and manipulation of their properties, thereby, enhancing the effectiveness of mucosal vaccines. This article reviews the recent literature and patents in the field of vaccine delivery using mucoadhesive polymeric carriers. What the reader will gain: The reader will gain insights into various natural polymers, synthetic polymers and ligand derived polymeric carrier systems studied to enhance mucosal immunization. Take home message: Biodegradable polymeric carriers represent a promising approach for mucosal delivery of vaccine.

Capsaicin delivery into the skin with lipidic nanoparticles for the treatment of psoriasis

Abstract The study aims to explore the potential of solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) in improving the topical delivery of capsaicin (CAP) by in vitro and in vivo studies. The lipidic nanoparticles were prepared by solvent diffusion method and were characterized for average particle size, zeta potential and entrapment efficiency. TEM photomicrographs revealed that the particles were nanometric in size. Higher amount of CAP can be encapsulated in the NLCs (87.4 ± 3.28) as compared with SLNs (79.7 ± 2.93%). The cumulative amounts of CAP permeated through the skin and retained in the SC were higher in the case of NLCs as compared with plain drug solution and SLNs. SLNs and NLCs exhibited minimum to no irritation. All the results concluded that NLCs and SLNs have shown a good ability to increase drug accumulation in the various skin layers but NLCs may be a more potential carrier for topical delivery of CAP for an effective therapy of psoriasis.

Influence of various lipid core on characteristics of SLNs designed for topical delivery of fluconazole against cutaneous candidiasis

Dermal delivery of fluconazole (FLZ) is still a major limitation due to problems relating to control drug release and achieving therapeutic efficacy. Recently, solid lipid nanoparticles (SLNs) were explored for their potential of topical delivery, possible skin compartments targeting and controlled release in the skin strata. The retention and accumulation of drug in skin is affected by composition of SLNs. Hence, the aim of this study was to develop FLZ nanoparticles consisted of various lipid cores in order to optimize the drug retention in skin. SLNs were prepared by solvent diffusion method and characterized for various in vitro and in vivo parameters. The results indicate that the SLNs composed of compritol 888 ATO (CA) have highest drug encapsulation efficiency (75.7 ± 4.94%) with lower particle size (178.9 ± 3.8 nm). The in vitro release and skin permeation data suggest that drug release followed sustained fashion over 24 h. The antifungal activity shows that SLNs made up of CA lipid could noticeably improve the dermal localization. In conclusion, CA lipid based SLNs are represents a promising carrier means for the topical treatment of skin fungal infection as an alternative to the systemic delivery of FLZ.

Effect of Surfactants on the Characteristics of Fluconazole Niosomes for Enhanced Cutaneous Delivery

Abstract: Fluconazole-loaded niosomes were prepared by the film hydration method with different surfactants (Span and Brij series) and characterized for various parameters. Results showed that niosomes composed of Span 40, Span 60, and Brij 72 were most stable with smaller size, i.e. 0.378 ± 0.022 μm, 0.343 ± 0.063 μm, and 0.287 ± 0.012 μm, respectively, along with higher entrapment efficiency (approx. > 41%). In vitro skin permeation and retention studies suggested that cutaneous accumulation was affected by surfactant property and vesicle size. Therefore the niosomes consisting of Span 40, Span 60, and Brij 72 surfactant are seemingly accumulated and form localized drug depots in the skin, thereby releasing the contents in a sustained manner and able to greatly enhance cutaneous retention of the drug.

Development and characterization of LTA-appended chitosan nanoparticles for mucosal immunization against hepatitis B

Abstract The present study was aimed at exploring the targeting potential of LTA-anchored chitosan nanoparticles (CH-NP) specifically to M cell following oral immunization. The lectinized CH-NP exhibited 7–29% coupling capacity depending upon the amount of glutaraldehyde added. Induction of the mucosal immunity was assessed by estimating secretory IgA level in the salivary, intestinal and vaginal secretions, and cytokine (IL-2 and IFN-γ) levels in the spleen homogenates. The results demonstrated that LTA-anchored CH-NP elicited strong humoral and cellular responses and hence could be a competent carrier-adjuvant delivery system for oral mucosal immunization against Hepatitis B.