Suresh P. Vyas

RGD-anchored magnetic liposomes for monocytes/neutrophils-mediated brain targeting.

Negatively charged magnetic liposomes were prepared using soya lecithin (Soya PC), cholesterol and phosphatidyl serine (PS) for their preferential presentation to circulating blood phagocytes (monocytes and neutrophils). PS ratio was optimized in terms of drug and magnetite loading, in vitro magnetic responsiveness and ex vivo monocytes/neutrophils uptake. RGD peptide was covalently coupled to the negatively charged liposomes composed of PC, cholesterol, PS and phopsphatidyl ethanolamine (PE) via carbodiimide-mediated coupling. In vivo cellular sorting study under magnetic guard indicated an increase in relative count of neutrophils and monocytes. Results suggest that selective uptake of RGD-anchored magnetic liposomes by these cells imparts them magnetic property. High levels of a model drug diclofenac sodium was quantified in target organ brain. In case of negatively charged uncoated magnetic liposomes brain levels of the drug was 5.95-fold compared to free drug and 7.58-fold in comparison to non-magnetic formulation, while for RGD-coated magnetic liposomes this ratio was 9.1-fold compared to free drug solution, 6.62-fold compared to non-magnetic RGD-coated liposomes and 1.5-fold when compared to uncoated magnetic liposomes. Liver uptake was significantly bypassed (37.2% and 48.3% for uncoated and RGD-coated magnetic liposomes, respectively). This study suggested the potential of negatively charged and RGD-coated magnetic liposomes for monocytes/neutrophils-mediated active delivery of drugs to relatively inaccessible inflammatory sites, i.e. brain. The study opens a new perspective of active delivery of drugs for a possible treatment of cerebrovascular diseases.

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.

Development and characterization of minoxidil-loaded liposomal system for delivery to pilosebaceous units

The current study aimed to deliver minoxidil (2,4-diamino-6-piperidinopyrimidine 3-oxide; MXD), a potent hypertrichotic agent, into the pilosebaceous units, exploring the potential of the liposomal system. MXD-loaded liposomes of different compositions were prepared by a thin-film hydration technique and subsequently characterized for various vesicle-specific attributes (i.e., size, shape, lamellarity, and entrapment efficiency). Comparative analysis among these compositions was conducted with reference to their vesicle-specific parameters, drug deposition, and drug-delivery mechanism toward pilosebaceous units. The latter may bring about a distinct change in MXD therapy for various ailments related to pilosebaceous units, such as alopecia. The in vitro drug release, ex vivo skin permeation, and drug-retention behavior of the prepared formulation were evaluated by employing rat skin (normal as well as pilosebaceous free) and semipermeable membrane. The results revealed that the neutral liposomes (mean vesicle size, 3.83 +/- 0.18 microm) showed maximum drug deposition in the pilosebaceous units among all the other tested formulations. A quantitative estimation of pilosebaceous delivery revealed that the concentration of MXD in each pilosebaceous unit decreased in the following order: neutral liposomal formulation (5.8 x 10(3) to 7.25 x 10(3) microg) > positively charged liposomal formulation (4.7 x 10(3) to 5.87 x 10(3) microg) > negatively charged liposomal formulation (4.2 x 10(3) to 5.25 x 10(3) microg) > nonliposomal formulation (1.6 x 10(3) to 2.0 x 10(3) microg). Stability studies construed the need to store the liposomal formulation at lower temperatures. The results of the current work indicate that the neutral liposomes can deliver the drug molecules into pilosebaceous units more effectively than the other studied formulations.

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.

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 Mediated Cytosolic Delivery of Drug, DNA and Proteins

Recent researches have focused on the development of a number of macromolecular drugs such as DNA, protein and drugs that are intended to exert their action in cytosol or other intracellular organelle. The major hurdle encountered in their in vivo utilization is endosomal escape of drugs. The advent in research on nanotechnology has offered a number of optional nanocarriers which demonstrate numerous advantages in specialized drug delivery applications. These advantages include stabilization, controlled release and site specific delivery of therapeutic molecules. In addition, the cytosolic delivery to subcellular compartments can also be achieved by inclusion of pH sensitive molecules (lipid, polymer or peptide) in nanocarrier construct to achieve endosomal escape. A number of molecules have been identified that in combination with nanocarriers mediate cytosolic delivery 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.

C-Type lectin receptor(s)-targeted nanoliposomes: an intelligent approach for effective cancer immunotherapy

AIMnThe purpose of present approach is to target C-Type lectin (CTL) receptors for preferential uptake by the macrophages/dendritic cells and improving the cross-presentation of ovalbumin.nnnMATERIALS & METHODSnConventional and engineered nanoliposomes (MPNLs) were fabricated and extensively characterized. The nanoliposome(s) was spherical in shape; and their ζ potential, size and ovalbumin loading efficiency were recorded to be 268 ± 4.15 nm, 23.4 ± 0.35 mV, 46.65 ± 1.84%, respectively.nnnRESULTSnThe findings demonstrate that MPNLs significantly improved the antigen uptake and its cross-presentation to evoke Th CD8+ cell-mediated cellular immunity.nnnCONCLUSIONnIn a nutshell, this engineered approach mannose surface modification for active targeting to dendritic cells/macrophages and pH-dependent quick endosomal antigen release is a promising system for efficient cancer immunotherapy.

Targeted Drug Delivery to the Mitochondria

Mitochondria are of an increasing interest in pharmaceutical and medical research since it has emerged as an intriguing target for treatment of many diseases with a great diversity of clinical appearance. The efficiency of drug action relies largely on how well it is able to reach its target or even its target inside the cell such as mitochondria. Subsequently, drug delivery to the specific intracellular organelle dramatically enhances drug action. Mitochondria play a major function in a range of cell processes and mitochondrial dysfunction contributes to several human diseases. Increasing interest in delivering large molecules such as nucleic acids, peptides, enzyme mimetics, drugs, and probes have led to the emergence of “Mitochondrial Medicine” as an entire pioneering field of biomedical exploration. Targeting of biologically active molecules to mitochondria in living cells open up ways for modifying mitochondrial functions, which may come with selective protection, repair or eradication of cells. Furthermore, nanoscience offers unique tools and materials to target therapeutic agents to mitochondria. This chapter deals with different aspects of mitochondrial drug delivery, current strategies of mitochondrial targeting and their possible therapeutic applications.

Polymeric Hydrogel: A Flexible Carrier System for Drug Delivery

Hydrogels are promising and innovative drug delivery system that plays a vital role by addressing the problems associated with old and modern therapeutics such as nonspecific effects and poor stability. Hydrogels are extensively being explored as drug delivery systems due to ease of their modifications and ability to efficiently encapsulate therapeutics of diverse nature through simple mechanisms. These are essentially based on hydrophilic polymer networks, with a tendency to imbibe water when placed in an aqueous environment. The affinity to aqueous solutions, superior colloidal properties, inertness in the biological system and the internal aqueous environment, make them suitable for incorporation of bulky drugs for delivery of chemotherapeutics and proteins. Present chapter presents introduction to hydrogel based drug delivery including types of hydrogel, their composition, types of polymerization techniques used for formulation of hydrogel and characterization of hydrogel. Furthermore, stimuli responsive hydrogels and their biomedical applications will be summarized.