Hybrid nanoparticles for the topical delivery of norfloxacin for the effective treatment of bacterial infection produced after burn.

The present study was designed to investigate the solubility and penetrability of norfloxacin after the topical application of developed lipid-polymer hybrid nanoparticle (LPN) formulation. The core shell of the LPNs formulation was composed of poly (lactic-co-glycolic acid) that is highly lipophilic in nature, thus control the release of drug. The developed formulations were characterised for size, shape (transmission electron microscopy [TEM], scanning electron microscopy [SEM], and atomic force microscopy), entrapment efficiency, Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC) and thermo gravimetric analysis (TGA). Moreover, in vitro skin permeation studies were performed to determine release profile of the drug. Norfloxacin loaded nanoparticles retained there antimicrobial efficacy against Staphylococcus aureus and Pseudomonas aeruginosa. Stability study was suggested that the suitable storage condition should be at 4 ± 2 °C/60 ± 5% RH for the LPNs. Therefore, these nanoparticles showed a safe and effective long-lasting approach for long treatment of bacterial infections due to burn.

Rationally designed block copolymer-based nanoarchitectures: An emerging paradigm for effective drug delivery.

Various polymeric materials have been investigated to produce unique modes of delivery for drug modules to achieve either temporal or spatial control of bioactives delivery. However, after intravenous administration, phagocytic cells quickly remove these nanostructures from the systemic circulation via the reticuloendothelial system (RES). To overcome these concerns, ecofriendly block copolymers are increasingly being investigated as innovative carriers for the delivery of bioactives. In this review, we discuss the design, fabrication techniques, and recent advances in the development of block copolymers and their applications as drug carrier systems to improve the physicochemical and pharmacological attributes of bioactives.

Theranostic Nanomedicine; A Next Generation Platform for Cancer Diagnosis and Therapy.

In the recent years, theranostic nanomedicine based strategies have gained much attention in the field of oncology particularly, in the development of new generation cancer diagnostic and therapeutic tools. Today, various approaches have been developed for bioactive(s) targeting to predefined pathological sites, as well as for quantification of physiological processes and visualization. Significant attempts have been made to combine therapeutic and diagnostic properties in to a single effective nanomedicine formulation. This concept, coined as "theranostics" is smart nanosystem(s), able to diagnose, bioactive(s) delivery and monitoring of therapeutic response. By combining therapeutic functionalities with molecular imaging, theranostic based strategies may be beneficial in the selection of therapy, planning of treatment, monitoring of objective response and planning of follow-up therapy based on the specific molecular characteristics of a disease. In this manuscript, we reviewed the recent development of theranostic approaches, various nanosystems as theranostic agents and applications of theranostic in cancer therapeutics and diagnostics.

Lipid-polymer hybrid nanoparticles: Development & statistical optimization of norfloxacin for topical drug delivery system.

Poly lactic acid is a biodegradable, biocompatible, and non-toxic polymer, widely used in many pharmaceutical preparations such as controlled release formulations, parenteral preparations, surgical treatment applications, and tissue engineering. In this study, we prepared lipid-polymer hybrid nanoparticles for topical and site targeting delivery of Norfloxacin by emulsification solvent evaporation method (ESE). The design of experiment (DOE) was done by using software to optimize the result, and then a surface plot was generated to compare with the practical results. The surface morphology, particle size, zeta potential and composition of the lipid-polymer hybrid nanoparticles were characterized by SEM, TEM, AFM, and FTIR. The thermal behavior of the lipid-polymer hybrid nanoparticles was characterized by DSC and TGA. The prepared lipid-polymer hybrid nanoparticles of Norfloxacin exhibited an average particle size from 178.6 ± 3.7 nm to 220.8 ± 2.3 nm, and showed very narrow distribution with polydispersity index ranging from 0.206 ± 0.36 to 0.383 ± 0.66. The surface charge on the lipid-polymer hybrid nanoparticles were confirmed by zeta potential, showed the value from +23.4 ± 1.5 mV to +41.5 ± 3.4 mV. An Antimicrobial study was done against Staphylococcus aureus and Pseudomonas aeruginosa, and the lipid-polymer hybrid nanoparticles showed potential activity against these two. Lipid-polymer hybrid nanoparticles of Norfloxacin showed the %cumulative drug release of 89.72% in 24 h. A stability study of the optimized formulation showed the suitable condition for the storage of lipid-polymer hybrid nanoparticles was at 4 ± 2 °C/60 ± 5% RH. These results illustrated high potential of lipid-polymer hybrid nanoparticles Norfloxacin for usage as a topical antibiotic drug carriers.

Capsaicin-loaded vesicular systems designed for enhancing localized delivery for psoriasis therapy.

The aim of the current investigation is to evaluate the potential of capsaicin (CAP)-containing liposomes, niosomes and emulsomes in providing localized and controlled delivery, to improve the topical delivery of drug. CAP-bearing systems were prepared by the film hydration method and compared through various in vitro and in vivo parameters. The TEM photographs suggested that the carrier systems were spherical in shape and nanometric in size range. Skin retention studies of CAP from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of the emul-gel formulation. Based on the results, we concluded that the emul-gel may be a potential approach for the topical delivery of CAP, for an effective therapy for psoriasis.

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

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.

Nanocarriers: a versatile approach for mucosal vaccine delivery.

Infectious agents generally use mucosal surfaces as entry port to the body thereby necessitating the need of development of mucosal vaccine as vaccination is important for disease avoidance and suppression. Vaccination through mucosal route is a promising strategy to elicit efficient immune response as parentally administered vaccines induce poor mucosal immunity in general. Safety, economy and stability are highly desired with vaccines and this can be achieved with use of delivery cargos. This review focuses on challenges related with mucosal vaccines and use of nanocarriers as suitable cargos to cater the antigen effectively to the desired site. The review also includes different factors which are to be considered regarding the performance of the nanocarriers and clinical status of these systems.

Polymer nanotechnology based approaches in mucosal vaccine delivery: challenges and opportunities.

Mucosal sites serve as the main portal for the entry of pathogens and thus immunization through mucosal routes can greatly improve the immunity. Researchers are continuously exploring the vaccination strategies to engender protective mucosal immune responses. Unearthing of mucosal adjuvants, that are safe and effective, is enhancing the magnitude and quality of the protective immune response. Use of nanotechnology based polymeric nanocarrier systems which encapsulate vaccine components for protection of sensitive payload, incorporate mucosal adjuvants to maximize the immune responses and target the mucosal immune system is a key strategy to improve the effectiveness of mucosal vaccines. These advances promise to accelerate the development and testing of new mucosal vaccines against many human diseases. This review focuses on the need for the development of nanocarrier based mucosal vaccines with emphases on the polymeric nanoparticles, their clinical status and future perspectives. This review focuses on the need and new insights for the development of nanoarchitecture governed mucosal vaccination with emphases on the various polymeric nanoparticles, their clinical status and future perspectives.

Dendritic cell-based vaccine research against cancer.

Therapeutic vaccines that treat cancers with the help of the patient's own immune system signify a feasible option for active immunotherapy against the disease. Dendritic cells (DCs) play a central role in modulating the immune response and thus can be wisely utilized as an immunotherapeutic strategy for cancer regimens. Advances in the knowledge of DC biology and function have led to the development of DC-based vaccines for cancer therapy. In the present review, we discuss the biology and function of DCs, their subsets and receptors, antigen loading and route of administration of DC vaccines, as well as active and passive targeting strategies for treating the cancer. We also discuss the preclinical and clinical status of these newly developed vaccines. Special attention should be given by the scientific community to the challenges that need to be solved for the successful implication of these vaccines in cancer therapy.

Tailored polymer-lipid hybrid nanoparticles for the delivery of drug conjugate: dual strategy for brain targeting.

The object of the present study was to investigate the glioma targeting propensity of folic acid (F) decorated polymer-lipid hybrid nanoparticles (PLNs) encapsulating cyclo-[Arg-Gly-Asp-D-Phe-Lys] (cRGDfK) modified paclitaxel (PtxR-FPLNs). The prepared PLNs were supposed to bypass the blood-brain barrier (BBB) efficiently and subsequently target integrin rich glioma cells. The developed formulations were characterized for size, shape, drug entrapment efficiency, and in vitro release profile. PtxR-FPLNs demonstrated highest in vitro inhibitory effect, cell apoptosis and cell uptake. Pharmacokinetics and biodistribution studies showed efficacy of PtxR-FPLNs in vivo. In vivo anti-tumor studies clearly revealed that the median survival time for Balb/C mice treated with PtxR-FPLNs (42 days) was extended significantly as compared to PtxR-PLNs (35 days), free PtxR (18 days), Ptx-FPLNs (38 days), Ptx-PLNs (30 days), free Ptx (14 days) and control group (12 days). From the results it can be concluded that the developed dual targeted nanoformulation was able to efficiently cross the BBB and significantly deliver higher amounts of drug to brain tumor for better therapeutic outcome.

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.

Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

Options and opportunities for clinical management and treatment of psoriasis.

Psoriasis is a complex, multifactorial disease that appears to be influenced by immune-mediated components. For many years the pathogenesis of psoriasis has been discordant; the clinical picture suggested that the psoriasis was secondary to abnormal keratinocyte proliferation and differentiation, but later the role of the T cell was revealed. A variety of treatment options range from topical agents (e.g., coal tar, dithranol, and emollients for milder forms) to systemic agents (i.e., methotrexate or cyclosporin), and phototherapy. Recently, biologics have been added to this list that target particular steps in the immune or inflammatory pathways. Various nanocarriers (e.g., liposomes, niosomes, and microemulsions) have been successfully exploited for the delivery of several antipsoriatic drugs. This review provides insight into various psoriasis treatment strategies-from conventional to novel-currently in use or in development as well as the novel targets that have been explored and/or investigated for anti-psoriatic therapy. The pathogenesis of psoriasis and some of the topical, systemic biological, and novel approaches currently in use or in development are reviewed here. The pros and cons of each treatment strategy are presented, as are some of the animal models used to study features reminiscent of psoriasis. This information can be used to better the understanding of treatment options for this disease.

Hyperbranched dendritic nano-carriers for topical delivery of dithranol.

The purpose of the current investigation was to explore the potential of polypropylene imine (PPI) dendrimers to deliver dithranol (DIT) topically and to evaluate its encapsulation, permeation and skin irritation potential. PPI (5.0 generation, 5.0 G) dendrimers and DIT-loaded PPI (DIT-PPI) were prepared and characterized by spectroscopy and transmission electron microscopy. DIT encapsulation, in vitro skin permeation study, skin irritation studies, fluorescent studies and tape stripping studies were performed. Loading of DIT was found to be pH dependent with maximum encapsulation at acidic pH (1.0 ± 0.02, 17.2 ± 0.56 and 57.1 ± 1.32% at 7.4, 5.5 and 1.2 pH, respectively). DIT-PPI showed significantly enhanced permeation rate constant and lesser skin irritation (11.61 ± 1.80 µg/cm(2)/h and 1.0, respectively) when compared with the plain DIT solution (2.72 ± 0.31 µg/cm(2)/h and 2.3, respectively). Skin separation studies and confocal laser scanning microscope images showed that the dye-loaded dendrimers exhibits deposition of dye in pilosebaceous compartment. These studies demonstrate that PPI can be exploited to improve the topical bioavailability of the molecules in a controlled pattern. The enhanced accumulation of DIT via dendrimer carrier within the skin might help optimize targeting of this drug to the epidermal and dermal sites, thus creating new opportunities for well-controlled, modern topical application of DIT for the treatment of psoriasis.

Multifunctional nanomedicines: potentials and prospects.

Nanotechnology is considered to be significant innovative revolution that have found wide spectrum of applications in the fields ranging from medicine, diagnostics, electronics, and communications. Currently used pharmaceutical nanocarriers, such as dendrimers, micelles, nanoparticles, polymeric nanoparticles, microspheres, and many of the nanocarriers particularly in the area of drug delivery, offer a wide variety of useful properties, such as longevity in the blood allowing for their accumulation in pathological areas particularly those with compromised vasculature; specific targeting to certain disease sites; enhanced intracellular penetration of nanomaterial with contrast properties allowing for the direct visualization of carrier in vivo, and stimuli sensitivity allowing for triggered drug release from the carriers under certain physiological conditions. Some of the pharmaceutical carriers have already made their way into clinic, while others are still under preclinical development. Moreover, the engineering of multifunctional nanocarriers with several useful properties can significantly enhance the efficacy of many therapeutic and diagnostic protocols. These novel materials operate at the nanoscale range and provide new and powerful cutting edge tools for imaging, diagnosis, and therapy. This review considers current standing and possible future directions in the emerging area of multifunctional nanocarriers with primary attention on the combination of such properties as longevity, targetability, intracellular penetration, and contrast loading.

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.