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Most of the active pharmaceutical ingredient used in the management of disease have poor water solubility and offer grueling problems in drug formulation development since low solubility is generally associated with poor dissolution characteristics which leads to poor oral bioavailability. The great challenge for the development of a pharmaceutical product is to create its new formulation and drug delivery system to limit solubility problems of existing drug candidate. Limited drug-loading capacity requires a large amount of carrier material to get appropriate encapsulation of the drug, which is another major challenge in the development of pharmaceutical product which could be resolved by developing nanocrystals (NCs). A significant research in the past few years has been done to develop NCs which helps in the delivery of poorly water soluble drugs via different routes. The technology could continue to thrive as a useful tool in pharmaceutical sciences for the improvement of drug solubility, absorption and bioavailability. Many crystalline compounds have pulled in incredible consideration much of the time, due to their ability to show good physical and chemical properties when contrasted with their amorphous counterparts. Nanocrystals have been proven to show atypical properties compared to the bulk. This review article explores the principles of the important nanocrystallization techniques including NCs characterization and its application.

Naloxone is an opioid receptor antagonist that can eradicate all pre-indications of the toxicity and inverse the opioid overdose. However, oral administration of naloxone offers limitations such as its extensive first-pass metabolism that results in poor therapeutic effects. In order to resolve this issue, we developed intranasal solid-lipid nanoparticles in which naloxone was incorporated for the higher brain disposition of naloxone with superior therapeutic effects for the reversal of toxicity of opioid overdose. The preparation of naloxone loaded solid-lipid nanoparticles was done by employing the solvent evaporation method. Later, the designed formulation was optimized by Quality by Design approach, specifically, Box-Behnken method. The composition of optimized formulation was Glyceryl monostearate as a solid lipid (40 mg), Pluronic127 (0.5%) and Tween 80 (0.1%) as a surfactant and co-surfactant, respectively. Furthermore, the characterization of optimized formulation was achieved in terms of particle size, PDI, zeta potential, entrapment efficiency, and drug loading which were 190.2 nm, 0.082, −16 mV, 95 ± 0.532% and 19.08 ± 0.106%, respectively. Afterwards, in vitro, ex vivo and in vivo experiments were performed in which higher drug release and superior drug uptake by nasal membrane were observed for naloxone-loaded solid-lipid nanoparticles, later it was confirmed by confocal microscopy of ex vivo nasal membrane tissue. The findings of gamma scintigraphy investigation exhibited better deposition of naloxone-loaded solid-lipid nanoparticles as compared to naloxone solution. Also, the better deposition of naloxone by gamma scintigraphy was further validated by the investigation through the biodistribution study. Additionally, the key findings of the pharmacokinetic study revealed Cmax, Tmax, AUC0-t, AUC0-∞, T1/2 and Ke was found to be 163.95 ± 2.64 ng/ml, 240 ± 2.1 min, 17.75 ± 1.08 ng.hr/ml, 18.82 ± 2.51 ng.hr/ml, 70.71 ± 0.115 min, 0.098 ± 0.01 h−1 respectively. Lastly, investigations such as weight variation and histopathological proved the plausible potential of naloxone-loaded solid-lipid nanoparticles in terms of safety as no toxicity was noticed even after the administration of the three-folds dose of the normal dose. Therefore, considering all these findings, it could be easy to say that these developed naloxone-loaded solid-lipid nanoparticles could be administrated via intranasal route and can act as successful novel nanoformulation for the effective treatment of opioid overdose.

Autoimmune diseases are collectively addressed as chronic conditions initiated by the loss of one’s immunological tolerance, where the body treats its own cells as foreigners or self-antigens. These hay-wired antibodies or immunologically capable cells lead to a variety of disorders like rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, multiple sclerosis and recently included neurodegenerative diseases like Alzheimer’s, Parkinsonism and testicular cancer triggered T-cells induced autoimmune response in testes and brain. Conventional treatments for autoimmune diseases possess several downsides due to unfavourable pharmacokinetic behaviour of drug, reflected by low bioavailability, rapid clearance, offsite toxicity, restricted targeting ability and poor therapeutic outcomes. Novel nanovesicular drug delivery systems including liposomes, niosomes, proniosomes, ethosomes, transferosomes, pharmacosomes, ufasomes and biologically originated exosomes have proved to possess alluring prospects in supporting the combat against autoimmune diseases. These nanovesicles have revitalized available treatment modalities as they are biocompatible, biodegradable, less immunogenic and capable of carrying high drug payloads to deliver both hydrophilic as well as lipophilic drugs to specific sites via passive or active targeting. Due to their unique surface chemistry, they can be decorated with physiological or synthetic ligands to target specific receptors overexpressed in different autoimmune diseases and can even cross the blood-brain barrier. This review presents exhaustive yet concise information on the potential of various nanovesicular systems as drug carriers in improving the overall therapeutic efficiency of the dosage regimen for various autoimmune diseases. The role of endogenous exosomes as biomarkers in the diagnosis and prognosis of autoimmune diseases along with monitoring progress of treatment will also be highlighted.

Steering drug-loaded, site-specific, coated lipid vesicles to the target receptor sites have the potential of plummeting adverse effects and improving the pharmacological response in diverse pathologies of the large bowel, especially the colon. Colonic delivery via oral route has its own challenges, often governed by several glitches such as drug degradation or absorption in the upper GIT, instability of proteins/peptides due to high molecular weight, and peptidase activity in the stomach. Consequently, colon-specific coated liposomal systems (CSLS) offer a potential alternate for not only site-specificity, but protection from proteolytic activity, and prolonged residence time for greater systemic bioavailability. On the other hand, liposomal delivery via the oral route is also cumbersome owing to several barriers such as instability in GIT, difficulty in crossing membranes, and issues related to production at the pilot scale. New advancements in the field of CSLS have successfully improved the stability and permeability of liposomes for oral delivery via modulating the compositions of lipid bilayers, adding polymers or ligands. Despite this ostensible propitiousness, no commercial oral CSLS has advanced from bench to bedside for targeted delivery to the colon as yet. Nevertheless, CSLS has quite fascinated the manufacturers owing to its potential industrial viability, simplistic and low-cost design. Hence, this review aims to decipher the convolutions involved in the engineering process of industrially viable CSLS for colonic delivery.

Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done. Finally, irinotecan loaded lignin nanoparticles (DLNPs) were synthesized to establish their drug carrying potential and thorough in vitro characterization was performed. BLNPs with controllable size (⁓152 nm), low polydispersity (0.2), maximized yield (65%), negative surface charge (-22 to -23 mV), spherical shape and smooth surface were obtained with acceptable %hemolysis (2%). In vitro cytotoxicity studies revealed that BLNPs were significantly toxic (74.38 ± 4.74%) in human breast adenocarcinoma (MCF-7), slightly toxic (38.8 ± 4.70%) in human alveolar epithelial adenocarcinoma (A-549) and insignificantly toxic (15.89 ± 2.84%) to human embryonic kidney (HEK-293) cells. BLNPs showed concentration dependent early neuronal defects in Drosophila, but nuclei fragmentation and gut cell damage were absent. Sustained release DLNPs with high drug loading reduced the IC

Amikacin (A), a water soluble aminoglycoside antibiotic is commercially available for intravenous administration only. Present investigation is aimed at the development of poly-lactic-co-glycolic acid (PLGA) nanoparticles (A-NPs). 1 for oral permeability enhancement of amikacin. The pharmaceutical attributes of the A-NPs revealed particle size, 260.3 ± 2.05 nm, zeta potential, −12.9 ± 1.12 mV and drug content, 40.10 ± 1.87 μg/mg with spherical shape and smooth surface. In vitro antibacterial studies showed that the A-NPs were active against P. aeruginosa, K. pneumoniae and E. coli. The permeation study across rat ileum showed 2.6-fold improvement in Papp for A-NPs than A-S 2 This increase in permeability is due to the uptake of nanoparticles by Peyer’s patches of intestinal epithelium and endocytic uptake via enterocytes. Flow cytometric analysis demonstrated 2.2-fold higher uptake of Rh B-NPs 3 than Rh B-S 4 and elucidated the dominance of enterocytes mediated endocytosis of nanoparticles. Furthermore, stability data collected as per ICH guidelines for three months under accelerated conditions had shown that the A-NPs were stable. The purported drug delivery system hence, seems a promising tool to replace successfully the current intravenous therapy and is used to support relevant patient compliance thereby, adding value to the “patient care at home”.

Osteoporosis is a major cause of morbidity, mortality, and economic burden worldwide. Despite being an effective in combating the bone-deteriorating disorders, bisphosphonates have several shortcomings including poor and variable bioavailability, low permeability, high toxicity, etc. In this study, we developed and optimized protransfersome formulation for the drug risedronate sodium (RIS-Na) with the goal of enhancing its bioavailability and hence patient compliance. Phase separation coacervation technique was utilized for development of optimized formulation. Optimization was achieved by using three-factor, three-level Box-Behnken design combined with Response Surface Methodology (RSM). This enabled us to decipher the effect of 3 independent variables (Phospholipid, Tween-80 and Sodium Deoxycholate) on three dependent parameters (entrapment efficiency, vesicle size and transdermal flux). Optimized formulation was further evaluated for pharmacokinetic and pharmacodynamic parameters. Smooth, spherical protransfersomes with a size of 260 ± 18 nm, having entrapment efficiency and flux of 80.4 ± 4.90% and 8.41 ± 0.148 μg/cm2/h, respectively were prepared. Ex vivo studies revealed a shorter lag time of 1.21 ± 0.18 h and higher flux associated with transdermal formulation. CLSM analysis further revealed better drug penetration (220 μm) through the skin in case of protransfersomes as compared to drug solution (72 μm). Additionally, biomechanical, biochemical, and histo-pathological studies further validated the results. Thus, it was concluded that protransfersome formulation has a great potential in providing better therapeutic efficacy of risedronate than its conventional counterpart.

A small, non-enveloped, obligatory parasite, Human papillomavirus (HPV) is known to be the cause of a range of malignancies. These entail benign infections like genital warts as well as malignant, life-threatening conditions such as cervical cancer. Since a very high mortality rate is associated with HPV caused cancers (cervical cancer is a 2nd leading cause of death caused due to cancer among women globally), there is an escalating need to understand and search for ways to combat such medical conditions. Under the same light, the given article provides an insight into the world of this versatile pathogen. Distinct aspects related to HPV have been discussed here. Emphasis has been laid upon the composition, function and assembly of capsid proteins (structural studies) and various genetic elements and their gene products (genomic studies). The essence of the mechanism behind the development of persistent infection and modes responsible for the transmission of the infectious particles has been briefly covered. Finally, the review outlines various infections and diseases caused by HPV with a major focus on their clinical and histological manifestations.

Chondroitin-4-sulfate (CS), a glycosaminoglycan, was used to prepare CS-capped super-paramagnetic iron oxide nanoparticles, which were further employed for loading a water-soluble chemotherapeutic agent (doxorubicin hydrochloride, DOX). CS-capped SPIONs have potential biomedical application in cancer targeting. The optimized formulation had a hydrodynamic size of 91.2±0.8nm (PDI; 0.228±0.004) and zeta potential of -49.1±1.66mV. DOX was loaded onto the formulation up to 2% (w/w) by physical interaction with CS. TEM showed nano-sized particles having a core-shell structure. XRD confirmed crystal phase of iron oxide. FT-IR conceived the interaction of iron oxide with CS as bidentate chelation and also confirmed DOX loading. Vibration sample magnetometry confirmed super-paramagnetic nature of nanoparticles, with saturation magnetization of 0.238emug(-1). In vitro release profile at pH 7.4 showed that 96.67% of DOX was released within 24h (first order kinetics). MTT assay in MCF7 cells showed significantly higher (p

Rheumatoid arthritis (RA) is a chronic, inflammatory, autoimmune disease of unidentified etiology that affects the joints and causes pain, swelling, stiffness and redness in the joints. The exact cause of rheumatoid arthritis has not yet been discovered and, consequently, treatment methods have not been optimally effective. It has long been treated with anti-inflammatory and immunosupressants including modern biologics either alone or in combination but all of the drugs have severe life threatening consequences with impaired immune function due to nonspecific targeting. Therefore, a three-pronged approach of local, active and synergistic targeting can be used to optimize delivery of therapeutic agents to reduce toxicity and patient outcome without compromising patient's immunity.

Overexpression of P-glycoprotein (P-gp) efflux transporter in glioma cells thwarts the build-up of therapeutic concentration of drugs usually resulting into poor therapeutic outcome. To surmount aforesaid challenge, Imatinib (IMM) loaded Poly-lactide-co-glycolic acid nanoparticles (IMM-PLGA-NPs) were developed and optimized by Box Behnken Design as a new treatment stratagem in malignant glioma. Optimized NPs were functionalized with Pluronic(®) P84, P-gp inhibitor (IMM-PLGA-P84-NPs) which showed size, PDI, zeta potential, drug loading, 182.63±13.56nm, 0.196±0.021, -15.2±1.49mV, 40.63±2.04μg/mg, respectively. Intracellular uptake study conducted on A172, U251MG and C6 glioma cells demonstrated significantly high uptake of IMM through NPs when compared with IMM solution (IMM-S), p

Most of the nanomedicines for treatment of multidrug-resistant cancer do not reach Phase III trials and many are terminated or withdrawn or are in an indeterminate state since long without any study results being presented. Extensive perusal of nanomedicine development research revealed that one of the critical aspects influencing clinical outcomes and which requires diligent scrutiny is selection process of nanodelivery system. Research papers and articles published on development of nanodelivery systems for treatment of multidrug-resistant cancer were analyzed. Observations and conclusions noted by these researchers which might shed some light on poor clinical performance of nanocarriers were collated and summarized under observation section. Further research articles were studied to find possible solutions which may be applied to these particular problems for resolving them. The inferences of these findings were composed in Result section. Plausible solutions for the observed obstacles were noted as examples of novel formulations that can yield the following: better in vivo imaging, precise targeting and dosing of a specific site and specific cell type in a particular cancer, modulation of tumor surroundings, intonation of systemic effects and high reproducibility. The angle of approach to the development of best nanosystem for a specific type of tumor needs to be spun around. Some of these changes can be brought about by individual scientists, some need to be established by collated efforts of scientists globally and some await advent of better technologies. Regardless of the stratagem, it can be said decisively that the schematics of development phase need rethinking.

Epirubicin (EPI) is a P-gp substrate antracycline analogue which elicits poor oral bioavailability. In the present work, EPI loaded poly-lactide-co-glycolic acid nanoparticles (PLGA-NPs) were prepared by double emulsion approach and superficially decorated with polyethylene glycol (EPI-PNPs) and mannosamine (EPI-MNPs). Average hydrodynamic particle size of EPI-PNPs and EPI-MNPs was found 248.63 ± 12.36 and 254.23 ± 15.16 nm, respectively. Cytotoxicity studies were performed against human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of EPI-PNPs and EPI-MNPs over free epirubicin solution (EPI-S). Further, confocal laser scanning microscopy (CLSM) and flow cytometric analysis (FACS) demonstrated enhanced drug uptake through EPI-PNPs and EPI-MNPs and elucidated dominance of caveolae mediated endocytosis for NPs uptake. Cellular transport conducted on human colon adenocarcinoma cell line (Caco-2) showed 2.45 and 3.17 folds higher permeability of EPI through EPI-PNPs and EPI-MNPs when compared with EPI-S (p

Colon cancer is one of the fatal forms of cancer all round the world with a equal frequency of occurrence in both male and female population. Mutational changes and defects in APC (Adenomatous Polyposis Coli) and DNA mismatch repair genes accompanied by genetic chaos in oncogenic pathways leads to colon cancer. Intensive study on pathogenesis of colon cancer has been made to decipher the mechanisms underlying the development and progress of the disease so as to develop effective treatment. However, a complete therapeutic regimen is still not available for combating this deadly disease. Hurdles faced by chemotherapy include drug resistance due to P-glycoprotein transporters, untoward effects on normal cells, high cost, bio-burden of the therapy, and the most dreadful drawback is cancer relapse. The concept of cancer relapse is related to development of oxidative stress that causes cell apoptosis. If the level of oxidative stress is inadequate to cause apoptosis then it leads to cell dormancy which may revive post chemotherapy. This hypothesis aims to put forward a combinatorial approach that includes utilizing a cost effective, biocompatible and environmentally benign nanoparticulate carrier made up of lignin, loaded with anti-cancer agent and P-gp modulator, and functionalized with ligand for CD44 receptors that are over expressed on cancer cells. Antioxidant effect of lignin will overcome dormancy of cancer cells making it possible for cell cycle specific drugs to kill them and prevent relapse and active targeting will prevent untoward effects on normal cells. Thus a robust and wholesome formulation can be developed to combat colon cancer.

Melanoma is the most serious form of skin cancer causing most of the skin cancer-related deaths. The incidence of melanoma has risen so dramatically over past few years that no other solid or blood malignancy comes close to it in terms of increased incidence. The main problem associated with the treatment of melanoma is low response rate to the existing treatment modalities, which in turn is due to the incomplete response by chemotherapeutic agents and inherent resistance of melanoma cells.Conventional therapeutic strategies, as well as, recent literature on melanoma have been thoroughly studied. This review summarizes the base of anti-melanoma treatment with conventional chemotherapeutic drugs, followed by an account of recent studies which explored the potential of nanotechnology and newer strategies and agents in melanoma treatment.Although melanoma is curable if detected in its early localized form, metastatic melanoma continues to be a therapeutic challenge. Metastatic melanoma has a very poor prognosis and conventional therapies have not improved the outcomes of the treatment so far. For this reason, newer combinations of anti-melanoma drugs and newer strategies utilizing nanotechnology have been constantly explored.

Multi Drug Resistance (MDR) of cancer cells is a constant threat to the clinically used drugs as well as new drug development. In present work, we aimed to assess

Melanoma is one of the most aggressive cancers which has very low response rate and survival rate. Melanoma cells are known to be inherently resistant to the chemotherapy which results in poor outcomes and even failure of the therapy. For this reason, a better understanding of underlying mechanism of melanoma pathogenesis and resistance is required, so that more efficient and novel therapeutic strategies can be developed. Survivin is a protein which is overexpressed in melanoma cells and is known to impart resistance to them against apoptosis. Also, melanoma cells overexpress Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) angiogenic growth factors which lead to aggressive angiogenesis in melanoma cells thereby making the treatment more challenging. This hypothesis presents a combinatorial approach against melanoma where an anti-survivin agent and an anti-angiogenic agent are combined with a chemotherapeutic drug and loaded in surface functionalized liposomes in order to target specific mechanisms of melanoma, thus overcoming its resistance. Thus, the study aims to overcome the resistance of melanoma cells by developing a wise combination of drugs and achieve a higher response rate in resistant melanoma model, which is usually not achieved with the existing treatment modalities.

Cancer remains one of the most deadly diseases worldwide, but conventional anticancer therapies come with several drawbacks. Therefore, there is a need to develop new anticancer strategies. Theranostics is a strategy that combines treatment with diagnosis and monitoring. Metal nanoparticles are proposed as one of the most promising theranostic agents for the treatment of cancer. Thus, metals including iron, gold (Au), silver (Ag), zinc (Zn), and titanium, have potential as anticancer agents, either inherently or as a result of surface modifications. As a functional component of theranostic tools, metal nanoparticles have crucial dual roles as a diagnostic and active therapeutic agent for the treatment of cancer.

Epirubicin (EPI) is an anthracycline antineoplastic agent, commercially available for intravenous administration only and its oral ingestion continues to remain a challenge. Present investigation is aimed at the development of poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for oral bioavailability enhancement of epirubicin. Developed formulation revealed particle size, 235.3±15.12 nm, zeta potential, -27.5±0.7 mV and drug content (39.12±2.13 μg/mg), with spherical shape and smooth surface. Cytotoxicity studies conducted on human breast adenocarcinoma cell lines (MCF-7) confirmed the superiority of epirubicin loaded poly-lactic-co-glycolic acid nanoparticles (EPI-NPs) over free epirubicin solution (EPI-S). Further, flow cytometric analysis demonstrated improved drug uptake through EPI-NPs and elucidated the dominance of caveolae mediated endocytosis for nanoparticles uptake. Transport study accomplished on human colon adenocarcinoma cell line (Caco-2) showed 2.76 fold improvement in permeability for EPI-NPs as compared to EPI-S (p0.001) whereas a 4.49 fold higher transport was observed on rat ileum; a 1.8 fold higher (p0.01) in comparison to Caco-2 cell lines which confirms the significant role of Peyer's patches in absorption enhancement. Furthermore, in vivo pharmacokinetic studies also revealed 3.9 fold improvement in oral bioavailability of EPI through EPI-NPs. Henceforth, EPI-NPs is a promising approach to replace pre-existing intravenous therapy thus providing "patient care at home".

In present investigation, we developed a novel hyaluronated cationic nanostructured lipid carrier (CNLCs) which contains CPT-11/irinotecan to target CD44 biomarker which commonly overexpresses on colon cancer. The cationic core NLCs was developed by using capmule MCM and compritol as mix lipid phase with 150 ± 2.5 nm particles size and 93.98 ± 2.5% entrapment efficiency. The cationic core NLCs were coated with hyaluronic acid by ionic conjugation. The particle size of hyaluronated CNLCs was enhanced to 255 ± 4.2 nm. In-vitro drug release studies revealed a slow and sustain release of the drug and a practically no leaching of coumarin-6. The confocal laser microscopy studies were performed with developed CNLCs in two CD44 overexpressing cell lines (HT-29 and Colo-320). The studies revealed marked uptake of the CNLCs by both the cell lines in just two hours. The results were comparable to the FITC conjugated CD44 antibodies. Therefore, the developed dual purpose CNLCs were found to be highly specific for CD44 biomarker. The developed formulations were found to be compatible with blood components. The MTT assay revealed that the developed particles had enhanced cytotoxicity against non-MDR as well MDR cancer cells.

Raloxifene, an anti-osteoporotic drug, is recently approved for prevention of breast cancer in postmenopausal women and thus the drug may be employed to combat the bony adverse effects of letrozole, another anticancer drug. However, the cytotoxic effect of their combination on human breast cancer (MCF-7) and human embryonic kidney (HEK) cell lines is not known. MCF-7 and HEK cell lines were treated with different graded doses of letrozole, raloxifene and their combination, then incubated for 24–48 h. MTT assay was performed to check the cytotoxicity of the drugs. The study indicates that the combination of letrozole and raloxifene possess additive effect in terms of cytotoxicity of cancer cell lines (MCF-7) and negligible effects in normal cell lines (HEK). Our study indicates that the addition of raloxifene doesn't interfere with anticancer efficacy of letrozole rather the combination acted additively for the treatment of breast cancer.

Background The CD44 receptor is a cell surface glycoprotein, which mediates many physiological and pathological activities. Its key role is to provide defence against inflammatory reactions by cellular transmigration and cell signalling. In pathological conditions, it gives destructive outcomes by mediating migration of pathogenic cells to vital organs resulting in tissue and organ damage. It binds to several ligands principally the hyaluronan. Objective This review explores CD44 structure, functions, and its potential as a disease indicator and therapeutic target. Method From a thorough literature review on the CD44 receptor, several patents of targeting approaches have been identified and herewith reviewed which recommend CD44-binding proteins, CD44-binding antibodies, antibody fragments, pharmaceutical compositions, as well as nucleic acids as a targeting moiety. Result Applicability of CD44 overexpression and its targeting has now been extensively utilized in the disease diagnosis and real-time bio imaging of pathologic cells. Conclusion A thorough understanding of CD44-receptor structure, expression and diverse functions towards different cell types would offer an opportunity to develop better therapeutic approaches in the near future by overcoming all the shortcomings of toxicity and efficacy. The present review includes recent patents of CD44 receptor targeting approaches that have been presented in the different agencies: European (EP), US, and World Intellectual Property Organization (WIPO) and a general analysis of the future developments and trends in this emerging area.

Zinc oxide (ZnO) nanoparticles (NPs) are a promising platform for use in biomedical research, especially given their anticancer and antimicrobial activities. These activities are associated with the ability of ZnO NPs to generate reactive oxygen species (ROS) and induce apoptosis. In addition, ZnO NPs have been successfully exploited as drug carriers for loading and transporting drugs to target sites, thereby reducing unwanted toxicity and off-target effects, and resulting in amplified synergistic effects. Here, we discuss the synthesis and biomedical applications of ZnO NPs.

The present work describes the preparation of sterically stabilize polymeric nanoparticles of mitoxantrone dihydrochloride (MTO) along with an efflux transporter (Pgp/BCRP) inhibitor that enhance the circulation time of nanoparticles and simultaneously surmount the problem of multidrug resistance (MDR). Mitoxantrone dihydrochloride being hydrophilic in nature had very low entrapment efficiency (%E.E.), thus in order to further enhance the lipophilicity and the %E.E., it was complexed with sodium deoxycholate (SDC) and this MTO-SDC-complex was used to formulate nanoparticles with/without Pgp/BCRP inhibitor by nanoprecipitation technique and was characterized for various in vitro and in vivo attributes. In vitro cell line studies were conducted on MCF7, A2780(p) and A2780(adr) cells. Furthermore, the targeting potential of hyaluronic acid (HA) coated nanoparticles for CD44 receptors was investigated using the MCF7 cell line. A reduction in the IC50 value observed with the inhibitor loaded nanoparticles in different cell lines indicated the BCRP/Pgp inhibiting ability of the formulated nanoparticles. The reduced macrophage uptake and the increased residence time in blood demonstrated the long circulating behaviour of the nanoparticles. The enhanced cellular uptake of HA coated nanoparticles in MCF7 cells revealed their targeting potential. The HA coated nanoparticles along with efflux transporter inhibitor exhibits a great potential for targeted chemotherapy in CD44 overexpressing MDR breast cancer.

The dual drug loaded poly( dl -lactic-co-glycolic acid) (PLGA 1 ) nanoparticles (TOP–TAM NPs 2 ) concurrently delivering topotecan hydrochloride (TOP 3 ) and tamoxifen citrate (TAM 4 ) were developed to achieve synergism for the treatment of breast cancer by enhancing the permeation of TOP through the gut and the cells present in the breast. TAM acted as P-glycoprotein (P-gp 5 ) inhibitor, reduced the side effects of individual drugs by reducing the dose. The NPs were prepared by double emulsion (w/o/w) method. The optimized TOP–TAM NPs were found to have smooth and spherical morphology by using SEM 6 and TEM 7 technique. Similarly size of nanoparticles was found to be 151.2 ± 1.6 nm with 0.147 ± 0.03 polydispersity index (PDI 8 ). The percentage entrapment efficiency of 95.17 ± 3.57 and 57.77 ± 2.2 was found for TAM and TOP respectively. The lyophillized nanoparticles under DSC 9 showed amorphous nature of both TOP and TAM. In an invitro release study the release of drugs from TOP–TAM NPs was found to follow the Higuchi pattern. The ex vivo gut permeation study revealed that the TAM enhanced the permeation of TOP and increased its bioavailability by 1.9 folds. The permeation and activity of combination of drugs were further confirmed by carrying out cell line studies on MCF-7 cells.

An insight into the complex cancer pathophysiology reveals that a dependable amelioration of the disease could only be envisaged with a multipronged treatment approach. It is highly evident that singular chemotherapeutic agents used in clinical practice have shown limitations like severe side effects, MDR and are often associated with poor QOL while combinations of drugs have yielded better therapeutic outcomes. The current hypothesis takes it a step forward wherein a chemotherapeutic agent is combined with a natural chemosensitizer, both loaded into a nanopotentiated particulate system, which would eventually deliver the drug cargo at the target site with certitude. The encapsulated natural bioactive would then favorably act on the tumor milieu through multiple portals and chemosensibilize the cells towards cytotoxic action of the synthetic drug moiety. This 2C (chemotherapeutic and chemosensitizer) approach along with nanosystem's attributes like high payload, prolonged action and diminished side effects would proffer a more dependable treatment modality. In conclusion, the proposed system would be a value addition to the currently available armamentarium of cancer treatment tools.

The present work evaluates the synergistic anticancer efficacy of bioactive Hydroxyapatite (HA) nanoparticles (HA NPs) loaded with Bendamustine HCl. Hydroxyapatite is a material with an excellent biological compatibility, a well-known fact which was also supported by the results of the Hemolytic studies and a high IC50 value observed in the MTT assay. HA NPs were prepared by the chemical precipitation method and loaded with the drug via physical adsorption. In-vitro release study was performed, which confirmed the sustained release of the drug from the drug loaded HA NPs. MTT assay, Cell Uptake and FACS studies on JURKAT E6.1 cell line and in-vivo pharmacokinetic studies in Wistar rats revealed that the drug loaded HA NPs could be easily internalized by the cells and release drug in a sustained manner. The drug loaded HA NPs showed cytotoxicity similar to the drug solution at 1/10th of the drug content, which indicates a possible synergism between the activity of the anticancer drug and calcium ions derived from the carrier. An increase in intracellular Ca(2+) ions is reported to induce apoptosis in cells. Tumor regression study in Balb/c mice Ehrlich's ascites model presented a similar synergistic efficacy. The drug solution was able to decrease the tumor volume by half, while the drug loaded HA NPs reduced the tumor size by 6 times.

The ATP-binding cassette superfamily contains membrane transporter proteins that transport a wide range of diverse compounds across cellular membranes. The P-glycoprotein (P-gp) is an important member of this family and a multi-specific drug efflux transporter that plays a significant role in governing the bioavailability of many clinically active drugs. The inhibition of this efflux transporter by various P-gp inhibitors forms a distinctive approach in improving bioavailability and conquering drug resistance. Most P-gp inhibitors exhibit limitations associated with their safety and unwanted pharmacokinetic interactions, thereby restraining their clinical applicability.This review explores the investigations on the feasibility and applicability of various classes of P-gp inhibitors as described in recent patents for enhanced drug delivery.Several candidates presently under development look promising as P-gp inhibitors, e.g., tariquidar and elacridar. Pharmaceutical excipients currently constitute the most promising class of P-gp inhibitors and are considered safe and pharmaceutically acceptable for use in formulations. In addition, lipid-based excipients and thiolated polymers play an active role in affecting P-gp-mediated transport not only by altering the membrane fluidity or ATPase activity but by down regulating P-gp expression. An additional overture such as the prodrug derivatization of P-gp substrates is a feasible approach to bypass P-gp-mediated efflux.

Niosomes represent an emerging class of novel vesicular systems. They are composed of nonionic surfactants which are biodegradable and relatively nontoxic. They were developed as stable and inexpensive alternatives to liposomes. Since their early introduction to cosmetic industry their role has diversified to other application areas. They are now being ardently explored as potential carriers for sustained and targeted drug delivery. In addition to conventional, oral, and parenteral routes, they are amenable to be delivered by ocular, transdermal, vaginal, and inhalation routes. Delivery of biotechnological products including vaccine delivery with niosomes is also an interesting and promising research area. The introduction of provesicular approach in the form of proniosomes has further increased the relevance of these systems. More concerted research efforts, however, are still required to realize the full potential of these novel systems. This review considers the current status and explores the potential of niosomes in drug delivery with special attention to their role in drug targeting. Their methods of preparation, formulation aspects, advantages, limitations, and applications are also discussed.

Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water, and surfactant, frequently in combination with a cosurfactant with a droplet size usually in the range of 20-200 nm. Since their discovery, they have attained increasing significance both in basic research and in industry. Due to their distinct advantages such as enhanced drug solubility, thermodynamic stability, facile preparation, and low cost, uses and applications of microemulsions have been numerous. Recently, there is a surge in the exploration of microemulsion for transdermal drug delivery for their ability to incorporate both hydrophilic (5-fluorouracil, apomorphine hydrochloride, diphenhydramine hydrochloride, tetracaine hydrochloride, and methotrexate) and lipophilic drugs (estradiol, finasteride, ketoprofen, meloxicam, felodipine, and triptolide) and enhance their permeation. Very low surface tension in conjunction with enormous increase in the interfacial area due to nanosized droplets of the microemulsion influences the drug permeation across the skin. A large number of oils and surfactants are available, which can be used as components of microemulsion systems for transdermal delivery but their toxicity, irritation potential, and unclear mechanism of action limit their use. Besides surfactants, oils can also act as penetration enhancers (oleic acid, linoleic acid, isopropyl myristate, isopropyl palmitate, etc.). The transdermal drug delivery potential of microemulsions is dependent not only on the applied constituents of the vehicle but also drastically on the composition/internal structure of the phases which may promote or hamper the drug distribution in the vehicles. This article explores microemulsion as transdermal drug delivery vehicles with emphasis on components selection for enhanced drug permeation and skin tolerability of these systems and further future directions.

Periodontal disease is a localised inflammatory response caused by the infection of a periodontal pocket arising from the accumulation of subgingival plaque. Periodontal disease has been considered as a possible risk factor for other systemic diseases such as cardiovascular diseases and pre-term low birth weight infants. Advances in understanding the aetiology, epidemiology and microbiology of periodontal pocket flora have revolutionised the therapeutic strategies for the management of periodontal disease progression. This review summarises the recent developments in the field of intra-pocket drug delivery systems and identifies areas where further research may lead to a clinically effective intra-pocket delivery system.

Microemulsions represent a promising carrier system for cosmetic active ingredients due to their numerous advantages over the existing conventional formulations. They are capable of solubilizing both hydrophilic and lipophilic ingredients with relatively higher encapsulation. There is growing recognition of their potential benefits in the field of cosmetic science in addition to the drug delivery. They are now being widely investigated for preparing personal care products with superior features such as having improved product efficiency, stability or appearance. They are well suited for the preparation of various cosmetic products for use as moisturizing and soothing agents, as sunscreens, as antiperspirants and as body cleansing agents. They are also valuable for use in hair care compositions which ensure a good conditioning of the hair as well as good hair feel and hair gloss. They have also found application in after shave formulations which upon application to the skin provide reduced stinging and irritation and a comforting effect without tackiness. These newer formulations elicit very good cosmetic attributes and high hydration properties with rapid cutaneous penetration which may accentuate their role in topical products. These smart systems are also suitable for perfuming purposes where minimum amount of organic solvents is required, such as for perfuming skin or hair. This article highlights the recent innovations in the field of microemulsion technology as claimed by different patents which can bring unique products with great commercial prospects in a very competitive and lucrative global cosmetic market.

Microemulsions are isotropic, thermodynamically stable transparent (or translucent) systems of oil, water and surfactant, frequently in combination with a cosurfactant with a droplet size usually in the range of 20-200 nm. They can be classified as oil-in-water (o/w), water-in-oil (w/o) or bicontinuous systems depending on their structure and are characterized by ultra low interfacial tension between oil and water phases. These versatile systems are currently of great technological and scientific interest to the researchers because of their potential to incorporate a wide range of drug molecules (hydrophilic and hydrophobic) due to the presence of both lipophilic and hydrophilic domains. These adaptable delivery systems provide protection against oxidation, enzymatic hydrolysis and improve the solubilization of lipophilic drugs and hence enhance their bioavailability. In addition to oral and intravenous delivery, they are amenable for sustained and targeted delivery through ophthalmic, dental, pulmonary, vaginal and topical routes. Microemulsions are experiencing a very active development as reflected by the numerous publications and patents being granted on these systems. They have been used to improve the oral bioavailability of various poorly soluble drugs including cyclosporine and paclitaxel as professed by Hauer et al., US patent 7235248, and Gao et al., US patent 7115565, respectively. Furthermore, they can be employed for challenging tasks such as carrying chemotherapeutic agents to neoplastic cells and oral delivery of insulin as diligently described by Maranhao, US patent 5578583 and Burnside et al., US patent 5824638 respectively. The recent commercial success of Sandimmune Neoral (Cyclosporine A), Fortovase (Saquinavir), Norvir (Ritonavir), etc. also reflects the tremendous potential of these newer drug therapeutic systems. A critical evaluation of recent patents claiming different approaches to improve the drug delivery is the focus of the current review.

The recognition of periodontal diseases as amenable to local antibiotherapy has resulted in a paradigmatic shift in treatment modalities of dental afflictions. Moreover the presence of antimicrobial resistance, surfacing of untoward reactions owing to systemic consumption of antibiotics has further advocated the use of local delivery of physiologically active substances into the periodontal pocket. While antimicrobials polymerized into acrylic strips, incorporated into biodegradable collagen and hollow permeable cellulose acetate fibers, multiparticulate systems, bio-absorbable dental materials, biodegradable gels/ointments, injectables, mucoadhesive microcapsules and nanospheres will be more amenable for direct placement into the periodontal pockets the lozenges, buccoadhesive tablets, discs or gels could be effectively used to mitigate the overall gingival inflammation. Whilst effecting controlled local delivery of a few milligram of an antibacterial agent within the gingival crevicular fluid for a longer period of time, maintaining therapeutic concentrations such delivery devices will circumvent all adverse effects to non- oral sites. Since the pioneering efforts of Goodson and Lindhe in 1989, delivery at gingival and subgingival sites has witnessed a considerable progress. The interest in locally active systems is evident from the patents being filed and granted. The present article shall dwell in reviewing the recent approaches being proffered in the field. Patents as by Shefer, et al. US patent, 6589562 dealing with multicomponent biodegradable bioadhesive controlled release system for oral care products, Lee, et al. 2001, US patent 6193994, encompassing a locally administrable, biodegradable and sustained-release pharmaceutical composition for periodontitis and process for preparation thereof and method of treating periodontal disease as suggested by Basara in 2004via US patent 6830757, shall be the types of intellectual property reviewed and presented in the current manuscript.

The aim of the present study was to formulate non-ionic surfactant vesicles of frusemide to enhance its skin permeation and to develop a transdermal therapeutic system using provesicular approach. The effect of various formulation variables on the transdermal flux, amount of drug deposited in skin, and plasma level of drug were studied. The skin permeation studies were conducted on rat skin and human skin for quantification of permeation parameters. With PGS3 formulation [Span 40:soyalecithin:cholesterol (4.5:4.5:1)], the plasma level in the rats had reached to a level of 0.42 +/- 0.13 microg/mL at the sampling interval of 4 hr and remained within the therapeutic concentration range (1.66-0.3 microg/mL) for the next 12 hr. Results showed that proniosomal formulation was able to sustain the drug level in the blood and offer a promising means for non-invasive delivery of frusemide.

A simple, sensitive, specific and high-resolution reversed-phase liquid chromatographic method utilizing ultraviolet detection has been developed and validated for simultaneous determination of topotecan and four intestinal permeability markers (atenolol, antipyrine, propranolol and furosemide) as suggested by US-FDA. Chromatography was carried out on C-18 column with mobile phase comprising water (pH 3.0) and acetonitrile gradient pumped at a flow rate of 1 ml min(-1). The validation parameters included specificity, accuracy, precision, sensitivity and stability studies. Topotecan, an anti-cancer drug widely used in metastatic carcinoma, is a P-glycoprotein substrate having oral bioavailability of 30% with large inter-patient variability. The present method was successfully applied for demonstrating P-gp mediated transport of topotecan and its inhibition using verapamil in Caco-2 cell monolayer. The method can be used in identification of novel P-gp inhibitors for topotecan and estimating the contribution of P-gp in affecting oral bioavailability of topotecan. The other applications of method include its use in validation of Caco-2 monolayer assay for getting biowaiver based on Biopharmaceutic Classification System and its extrapolation to in situ and/or in vivo studies.

Typically, chemotherapy has been dominated by intravenous administration. Though, inclination towards oral ingestion of chemotherapeutics is increasing since it offers ample of fascinating opportunities including better quality of life, treatment advantages and low healthcare cost. However, low or moderate bioavailability along with significant inter-patient variability and narrow therapeutic window challenges their oral administration. Thus, optimization of oral route with maximized efficacy and miniminal adverse events is a challenging area. To surmount the challenges, a number of strategies like P-glycoprotein (P-gp) modulation, colloidal carrier etc. have been under investigation and scientists are exploring the utility of solid dispersions, prodrugs, biconjugates, complexes, microparticulate, and nanoparticulate systems (liposome, SLN, dendrimers, SEDDS, nanoparticles). Among these, nanoparticulate systems have shown promising results due to their targeting potential and ability to alter absorption pathways. Functional excipients with P-gp modulating activity are also being explored for more effective oral delivery of chemotherapeutics. This article explores the encouraging reports, recent patents and inventions on the feasibility and applicability of oral administration of chemotherapeutics.

Imatinib mesylate has been evaluated for possible potential in treatment of colon cancer in recent times. However, due to significant reporting of P-gp expression in colon cancer, it can come across set back due to MDR. Therefore, in present work the liposomal formulation containing imatinib-bile salt conjugate was developed and investigated for its comparative performance in MDR colon cancer cells and surface modified with hyaluronic acid for achieving low hemotoxicity with stealth characteristics. Imatinib was successfully conjugated with sodium-deoxycholate by charged conjugation and evaluated through FTIR, DSC and PXRD. The developed conjugate (IM-SD) was encapsulated in liposomes and the conditions were optimized by Box-Behnken statistical design to achieve a size of 56.56±1.23 nm along with 99.11±0.89% entrapment efficiency (LIPO). The liposomes were surface modified with hyaluronic acid and the size was enhanced to 159.14±3.2 nm (HA-LIPO). Flow cytometric studies demonstrated the enhanced uptake of P-gp substrate rhodamine dye in P-gp positive colo 320 colon cancer cells. In addition, an enhanced cellular internalization of HA-LIPO in CD-44 positive HT-29 and colo 320 cells indicates the targeting attributes of the hyaluronan coated liposomes. Finally, the hyaluronan coated liposomes were also found to have low opsonization activity.

Irinotecan loaded nanostructured lipid carrier (NLC-Ir) was surface decorated with hyaluronic acid graft polymer. Hyaluronic acid is a biocompatible, non-antigenic and hydrophilic, CD-44 ligand that can impart many useful features to the nanocarrier for anticancer drug delivery. The present investigation demonstrated that hyaluronic acid coated HA-NLC had significantly lower haemolytic potential as compared to uncoated NLC. Further, HA-NLC had a reduced plasma protein interaction and low macrophage uptake. The in vivo tumor targeting and pharmacodynamics efficacy of HA-NLC was studied in Ehrlich's Ascites Tumor (EAT) allograft model. Radio scintigraphic biodistribution studies revealed that HA-NLC carrier got accumulated in the tumor tissues in good proportion. Additionally, the content of radioactivity associated with tumor tissues remained constant at 2, 4 and 24 h (2.41, 2.48 and 2.47%, respectively), while it got reduced in other organs. Furthermore, tumor to muscle ratio of radioactivity suggested a better accumulation of HA-NLC in tumor tissues that was significantly enhanced (P

Over expression of P-glycoprotein (P-gp) in cancer cells often results in highly aggressive, multi-drug resistant (MDR) phenotype. Such tumors are very difficult to treat with conventional therapy and often lead to failure of the treatment. In this work, we fabricated surface engineered hybrid lipid nanoparticles grafted with novel AL-HA polymer by mineralization technique. AL-HA graft polymer was prepared by covalent conjugation of alendronate sodium and hyaluronic acid. Compritol ATO 888 and capmule MCM C8 hybrid lipid mix was employed to prepare irinotecan containing nanostructured lipid carrier (NLC) by using functional excipients with P-gp inhibition activity. AL-HA was successfully grafted over NLC-Ir (uncoated irinotecan loaded NLC) by calcium-assisted mineralization. HA-NLC-Ir (hyaluronic acid coated irinotecan loaded NLC) particles have a nanoscale size of 386±2.2 nm along with a zeta potential value of 19.7±1.2 mV. NLC-Ir as well as HA-NLC-Ir showed a slow and sustained drug release. In vitro cell line studies performed on HT-29 and Colo-320 colon cancer cells revealed a reduced IC50 even in MDR cells. Flowcytometry studies demonstrated the capability of the developed nanocarriers to deliver the P-gp substrate moieties in MDR cancer cells. Furthermore, the targeting potential of HA-NLC was confirmed by CLSM studies. The cell line studies also revealed that NLC formulation had a potential of inhibiting P-gp by affecting ATPase activity and MDR1 gene expression.

A receptor level interaction of etoposide with P-glycoprotein (P-gp) and subsequent intestinal efflux has an adverse effect on its oral absorption. The present work is aimed to enhance the bioavailability of etoposide by co-administering it with quercetin (a P-gp inhibitor) in dual-loaded polymeric nanoparticle formulation. Poly-lactic-co-glycolic acid (PLGA) nanoparticles were optimized for various parameters like o/w phase volume ratio, poly-vinyl alcohol concentration, PLGA concentration and sonication time. The cytotoxicity studies (MTT assay) revealed a 9- and 11-fold decrease in the IC 50 values for etoposide-loaded nanoparticles (ENP) and etoposide + quercetin dual-loaded nanoparticles (EQNP) when compared to that of free etoposide, respectively, and the results were further supported by florescent-activated cell sorter studies. The confocal imaging of the intestinal sections treated with ENP and EQNP containing fluorescent probe (rhodamine) showed the superiority of the EQNP to permeate deeper. Furthermore, pharmacokinetic studies on rats revealed that EQNP exhibited a 2.4-fold increase in bioavailability of etoposide than ENP with no quercetin. The developed loaded nanoparticles have the high potential to enhance the bioavailability of the etoposide and sensitize the resistant cells.

Multidrug resistance (MDR) is an area of concern for the drug developers as well as clinical practitioners. This phenomenon is putting an emance pressure on treatment modalities of many diseases as well as posing a grave danger over clinically accepted drugs as well as molecules under clinical development. P-glycoprotein (P-gp) mediated efflux of xenobiotics is one of the major mechanisms involved in MDR. Hence, an effective modulation of P-gp may restore the potential of many substrate drugs. However, the non-specific P-gp modulation may be associated with many unwanted toxic effects. Therefore, an approach involving simultaneous exploitation of P-gp modulation as well as targeted delivery in a particulate carrier system may result in a more effective MDR reversal, accompanying a safer drug profile.

The purpose of this work is intended to investigate the potential of self-nanoemulsifying (SNE) drug delivery system for enhanced oral bioavailability of etoposide by P-glycoprotein (P-gp) modulation. The components of SNE formulation were optimized by their solubilization and emulsification efficiency. The ternary phase diagrams provided nanoemulsion existence ranges and the corresponding formulations were developed and evaluated via thermodynamic and dispersibility tests. The successful formulations were characterized for various parameters including time required for self-emulsification, percentage transmittance, droplet size, surface morphology, zeta potential and in vitro release. The etoposide loaded SNE9 formulation showed 2.6- and 11-fold higher permeability coefficient in apical to basolateral direction across Caco-2 monolayers as compared to the Etosid and plain drug solution, respectively. The etoposide loaded SNE9 formulation showed a higher cytotoxicity at the highest tested concentration compared to the blank SNE9 formulation and the free etoposide. Furthermore, an in vivo pharmacokinetic study of etoposide in SNE9 formulation showed 3.2- and 7.9-fold increase in relative oral bioavailability compared with that of etoposide in Etosid and drug suspension, respectively. Thus, the developed SNE drug delivery system could be a valuable tool for the effective oral delivery of etoposide.

The singular aim of the proposed work is the development of a synergistic thermosensitive gel for vaginal application in subjects prone to recurrent vaginal candidiasis and other microbial infections. The dual loading of Itraconazole and tea tree oil in a single formulation seems promising as it would elaborate the microbial coverage. Despite being low solubility of Itraconazole in tea tree oil, a homogeneous, transparent and stable solution of both was created by co-solvency using chloroform. Complete removal of chloroform was authenticated by GC–MS and the oil solution was used in the development of nanoemulsion which was further translated into a gel bearing thermosensitive properties. In vitro analyses (MTT assay, viscosity measurement, mucoadhesion, ex vivo permeation, etc.) and in vivo studies (bioadhesion, irritation potential and fungal clearance kinetics in rat model) of final formulation were carried out to establish its potential for further clinical evaluation.

Irinotecan is a camptothecin derivative with low oral bioavailability due to active efflux by intestinal P-glycoprotein receptors. Hence, no oral formulation is marketed for Irinotecan till date. However, an optimized Self micro emulsifying drug delivery system (SMEDDS), formulated to produce nano range oil droplets by using P-gp modulator excipients can tackle the issue and elevate the systemic availability of Irinotecan. The present work focuses on the development of SMEDDS for Irinotecan and evaluation of its in vitro, ex vivo and in vivo potentials. The SMEDDS were developed using Capmul MCM-C8, Cremophor EL and Pluronic L-121 as oil, surfactant and co-surfactant respectively and has good oil carrying capacity (30%) with competence to produce nano-scale oil droplets (130 ± 2.13 nm) on spontaneous emulsification. A much deeper penetration to the intestine was observed with SMEDDS by using confocal laser scanning microscopy (CLSM). Flow-cytometric studies also revealed the greater uptake of fluorescent probe in Caco-2 cell-lines with the use of SMEDDS. Biochemical estimation of LDH from the intestinal tissues treated with SMEDDS and free drug suspension confirmed that the developed formulation is safe for use. Furthermore, the AUC 0 → t of Irinotecan from the optimized SMEDDS formulation was found to be 4 folds higher than that from Irinotecan suspension on oral administration. The optimized SMEDDS formulation was found to be capable of maintaining the sustained plasma drug level of Irinotecan with better bioavailability.

CD44 or hyaluronan receptor is a transmembrane receptor associated with aggressive tumour growth, proliferation, and metastasis. In normal physiology, this receptor has a crucial role in cell adhesion, inflammation, and repair processes. However, many tumour cells over-express this receptor and abuse it to become progressive and perpetual units. The article comments from common functioning of the CD44 receptor, to its diabolic multi-dimensional effects in promotion of malignant cells. It also illuminates the relations of CD44 endorsed processes with other biomolecular events in cancer progression. In an end, the review focuses comprehensively at ongoing researches to exploit the CD44 over-expression as a probable target in treatment, management, and diagnosis of malignancy.

This study was aimed to develop chitosan coupled lipid nanoparticle (Ch-Ptx-Lip), where immunomodulatory activity of chitosan and chemotherapeutic effect of paclitaxel can synergistically enhance efficacy of this novel drug delivery system. Particle size, zeta potential and % Entrapment Efficiency (%EE) of Ch-Ptx-Lip was found to be 113.3 +/- 4.5 nm (PDI: 0.38), (+)35.7 +/- 2.9 mV and 96.4 +/- 1.8% respectively. Morphological evaluation of these particles by TEM shows circular bilayer structure along with outer polymer layers. Ch-Ptx-Lip showed significantly enhanced cytotoxicity (p < 0.05) compared with marketed formulation (Ptx Solution) and Ptx-Lip when evaluated in-vitro by MTT assay on MCF-7 cell lines. Improved efficacy with lower dose of drug can be a new strategy against cancer with minimum side effects and shorter treatment duration.

Ever since transdermal drug delivery came into existence, it has offered great promises, although most of them are yet to be fulfilled owing to some intrinsic restrictions of the transdermal route. On the positive side, transdermal drug delivery systems present advantages including non-invasiveness, prolonged therapeutic effect, reduced side effects, improved bioavailability, better patient compliance and easy termination of drug therapy. The greatest hindrance in the percutaneous delivery is the obstruction property of the stratum corneum, the outermost layer of the skin, in addition to usual problems such as skin binding, skin metabolism, cutaneous toxicity and prolonged lag times.This paper reviews investigations on the feasibility and application of penetration enhancers as described in recent patents, which help in the selection of a suitable sorption promoter(s) for enhanced delivery of medicaments through the skin.The patents granted under various categories of penetration enhancers have been discussed including fatty acids, terpenes, fatty alcohol, pyrrolidone, sulfoxides, laurocapram, surface active agents, amides, amines, lecithin, polyols, quaternary ammonium compounds, silicones, alkanoates and so on.Scores of promising chemicals have been harnessed for their skin permeation promoting capacity as mentioned earlier. In future, many more chemicals and putative enhancers are likely be documented and patented.

Transdermal drug delivery system has been accepted as potential non-invasive route of drug administration, with advantages of avoidance of the first-pass metabolism, sustained therapeutic action and better patient compliance, though, its prevalent use is restricted due to excellent impervious nature of skin. It is the greatest challenge for researchers to surmount the inherent limitations imposed by stratum corneum of skin, for enhanced transdermal drug delivery to achieve systemic therapeutic concentration. Thus, many approaches have been attempted to perturb skin barrier and enhance the transdermal delivery of drug. The major approaches for enhancing transdermal delivery are physical enhancers (ultrasound, iontophoresis, electroporation, magnetophoresis, microneedle), vesicles, particulate systems (liposome, niosome, transfersome, microemulsion, solid lipid nanoparticle) and chemical enhancers (sulphoxides, azones, glycols, alkanols, terpenes etc.). The present review explores recent patents on techniques employed to breach the skin barrier for drug permeation along with their penetration enhancement mechanisms.

Considerable research efforts have been directed towards understanding the enigma of P-glycoprotein (P-gp) in drug development and delivery. P-gp is a multi-specific drug efflux transporter that plays a significant role in governing the bioavailability of various anti-cancer drugs. Modulation of this efflux transporter by various traditional 'chemosensitisers' forms a distinctive approach in improving pharmacokinetics and conquering drug resistance. However, such inhibitors show limitations associated with their safety and unwanted pharmacokinetic drug interaction restraining their clinical applicability. To address these concerns, several research groups have used pharmaceutical excipients (functional excipients or additives) to inhibit P-gp and enhance drug permeability. This article focuses on such excipients, various co-development strategies for the formulation of cytotoxic drugs with this multi-drug resistance (MDR) reversing additives.