Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc) in the treatment of various diseases The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (eg, natural products) and selective diagnosis through disease marker molecules The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed In addition, we have included information regarding the trends and perspectives in nanomedicine area

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Nano based drug delivery systems: recent developments and future prospects

Targeted delivery combined with controlled drug release has a pivotal role in the future of personalized medicine. This review covers the principles, advantages, and drawbacks of passive and active targeting based on various polymer and magnetic iron oxide nanoparticle carriers with drug attached by both covalent and noncovalent pathways. Attention is devoted to the tailored conjugation of targeting ligands (e.g., enzymes, antibodies, peptides) to drug carrier systems. Similarly, the approaches toward controlled drug release are discussed. Various polymer–drug conjugates based, for example, on polyethylene glycol (PEG), N-(2-hydroxypropyl)methacrylamide (HPMA), polymeric micelles, and nanoparticle carriers are explored with respect to absorption, distribution, metabolism, and excretion (ADME scheme) of administrated drug. Design and structure of superparamagnetic iron oxide nanoparticles (SPION) and condensed magnetic clusters are classified according to the mechanism of noncovalent drug loading involving...

Targeted Drug Delivery with Polymers and Magnetic Nanoparticles: Covalent and Noncovalent Approaches, Release Control, and Clinical Studies.

Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. For the treatment of human diseases, nasal and pulmonary routes of drug delivery are gaining increasing importance. These routes provide promising alternatives to parenteral drug delivery particularly for peptide and protein therapeutics. For this purpose, several drug delivery systems have been formulated and are being investigated for nasal and pulmonary delivery. These include liposomes, proliposomes, microspheres, gels, prodrugs, cyclodextrins, among others. Nanoparticles composed of biodegradable polymers show assurance in fulfilling the stringent requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time.

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Drug delivery systems: An updated review.

The RNA interference (RNAi) pathway regulates mRNA stability and translation in nearly all human cells. Small double-stranded RNA molecules can efficiently trigger RNAi silencing of specific genes, but their therapeutic use has faced numerous challenges involving safety and potency. However, August 2018 marked a new era for the field, with the US Food and Drug Administration approving patisiran, the first RNAi-based drug. In this Review, we discuss key advances in the design and development of RNAi drugs leading up to this landmark achievement, the state of the current clinical pipeline and prospects for future advances, including novel RNAi pathway agents utilizing mechanisms beyond post-translational RNAi silencing.

The current state and future directions of RNAi-based therapeutics.

Nanoparticle-liver interactions: Cellular uptake and hepatobiliary elimination

Asialoglycoprotein receptor mediated hepatocyte targeting - strategies and applications.

Polyethylene glycol-phosphatidylethanolamine conjugate (PEG-PE)-based mixed micelles: some properties, loading with paclitaxel, and modulation of P-glycoprotein-mediated efflux.

The present study evaluates freeze thaw as a simple approach for screening the most appropriate cryoprotectant. Freeze–thaw study is based on the principle that an excipient, which protects nanoparticles during the first step of freezing, is likely to be an effective cryoprotectant. Nanoparticles of rifampicin with high entrapment efficiency were prepared by the emulsion-solvent diffusion method using dioctyl sodium sulfosuccinate (AOT) as complexing agent and Gantrez AN-119 as polymer. Freeze–thaw study was carried out using trehalose and fructose as cryoprotectants. The concentration of cryoprotectant, concentration of nanoparticles in the dispersion, and the freezing temperature were varied during the freeze–thaw study. Cryoprotection increased with increase in cryoprotectant concentration. Further, trehalose was superior to fructose at equivalent concentrations and moreover permitted use of more concentrated nanosuspensions for freeze drying. Freezing temperature did not influence the freeze–thaw study. Freeze-dried nanoparticles revealed good redispersibility with a size increase that correlated well with the freeze–thaw study at 20% w/v trehalose and fructose. Transmission electron microscopy revealed round particles with a size ∼400 nm, which correlated with photon correlation spectroscopic measurements. Differential scanning calorimetry and X-ray diffraction suggested amorphization of rifampicin. Fourier transfer infrared spectroscopy could not confirm interaction of drug with AOT. Nanoparticles exhibited sustained release of rifampicin, which followed diffusion kinetics. Nanoparticles of rifampicin were found to be stable for 12 months. The good correlation between freeze thaw and freeze drying suggests freeze–thaw study as a simple and quick approach for screening optimal cryoprotectant for freeze drying.

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Freeze thaw: a simple approach for prediction of optimal cryoprotectant for freeze drying.

Doxorubicin remains the first line of treatment for various cancers ever since its discovery in 1971. Cardiotoxicity and nephrotoxicity associated with unformulated doxorubicin triggered the development of doxorubicin nanocarriers. Although the therapeutic profile of doxorubicin is appreciably improved by entrapping in nanocarriers, they are largely taken up by organs of the reticuloendothelial system. Engineered nanocarriers of doxorubicin refer to carriers modified to escape recognition by reticuloendothelial system and/or functionalized with target specific ligands for selective accumulation at the target site. The first developments in engineered nanocarriers were the stealth carriers. These effectively bypassed the reticuloendothelial system and enhanced the therapeutic profile of doxorubicin by enabling passive accumulation in tumors. Stealth nanocarriers of doxorubicin revealed significant decrease in cardiotoxicity and nephrotoxicity, which led to the approval of liposomal doxorubicin for clinical applications. Success of liposomal doxorubicin was soon dulled by the appearance of newer toxicities like palmar-plantar erythrodysesthesia commonly referred as hand foot syndrome. The search for the magic bullet of doxorubicin has further intensified and resulted in design of engineered nanocarriers with high specificity for cancer cells. This review charts the progress from nanocarriers to engineered nanocarriers of doxorubicin, and highlights the current status of engineered nanocarriers of doxorubicin in clinical trials.

Padma V. Devarajan

Papers

Asialoglycoprotein receptor mediated hepatocyte targeting - strategies and applications.

Polyethylene glycol-phosphatidylethanolamine conjugate (PEG-PE)-based mixed micelles: some properties, loading with paclitaxel, and modulation of P-glycoprotein-mediated efflux.

Freeze thaw: a simple approach for prediction of optimal cryoprotectant for freeze drying.

Engineered nanocarriers of doxorubicin: a current update.

Targeted Drug Delivery : Concepts and Design