Etodolac Containing Topical Niosomal Gel: Formulation Development and Evaluation.

The present study aimed to investigate the delivery potential of Etodolac (ETD) containing topical niosomal gel. Niosomal formulations were prepared by thin film hydration method at various ratios of cholesterol and Span 60 and were evaluated with respect to particle size, shape, entrapment efficiency, and in vitro characteristics. Dicetyl phosphate (DCP) was also added in the niosomal formulation. Mean particle size of niosomal formulation was found to be in the range of 2 µm to 4 µm. Niosomal formulation N2 (1 : 1) ratio of cholesterol and surfactant displayed good entrapment efficiency (96.72%). TEM analyses showed that niosomal formulation was spherical in shape. Niosomal formulation (N2) displayed high percentage of drug release after 24 h (94.91) at (1 : 1) ratio of cholesterol : surfactant. Further selected niosomal formulation was used to formulate topical gel and was characterized with respect to its various parameters such as pH, viscosity, spreadability, ex vivo study, and in vivo potential permeation. Ex vivo study showed that niosomal gel possessed better skin permeation study than the plain topical gel. Further in vivo study revealed good inhibition of inflammation in case of topical niosomal gel than plain gel and niosomal formulation. The present study suggested that topical niosomal gel formulations provide sustained and prolonged delivery of drug.

In Vitro and In Vivo Evaluation of Niosomal Formulation for Controlled Delivery of Clarithromycin.

The present study was focused on formulating and evaluating clarithromycin (CLR) containing niosomal formulation for in vitro and in vivo pharmacokinetic behavior. Niosomal formulations (empty and drug loaded) were prepared by using different ratio of surfactant (various Span grades 20, 40, 60, and 80) and cholesterol by thin film hydration method and were evaluated for in vitro characteristics, stability studies, and in vivo study. Dicetyl phosphate (DCP) was added to the niosomal formulation. Various pharmacokinetic parameters were determined from plasma of male SD rats. Span 60 containing niosomal formulation NC2 (cholesterol to surfactant ratio 1 : 1) displayed highest entrapment efficiency with desired particle size of 4.67 µm. TEM analyses showed that niosomal formulation was spherical in shape. Niosomes containing Span 60 displayed higher percentage of drug release after 24 h as compared to other formulations. NC2 formulation was found to be stable at the end of the study on storage condition. Various pharmacokinetic parameters, namely, AUC, AUMC, and MRT of niosomal formulation, were found to be 1.5-fold, 4-fold, and 3-fold plain drug, respectively. The present study suggested that niosomal formulations provide sustained and prolonged delivery of drug with enhance bioavailability.

QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride.

The objectives of present studies were to develop the systematically optimized multiple-unit gastroretentive microballoons, i.e. hollow microspheres of itopride hydrochloride (ITH) employing quality by design (QbD)-based approach. Initially, the patient-centric QTPP and CQAs were earmarked, and preliminary studies were conducted to screen the suitable polymer, solvent, solvent ratio, pH and temperature conditions. Microspheres were prepared by non-aqueous solvent evaporation method employing Eudragit S-100. Risk assessment studies carried out by constructing Ishikawa cause-effect fish-bone diagram, and techniques like risk estimation matrix (REM) and failure mode effect analysis (FMEA) facilitated the selection of plausible factors affecting the drug product CQAs, i.e. percent yield, entrapment efficiency (EE) and percent buoyancy. A 3(3) Box-Behnken design (BBD) was employed for optimizing CMAs and CPPs selected during factor screening studies employing Taguchi design, i.e. drug-polymer ratio (X1), stirring temperature (X2) and stirring speed (X3). The hollow microspheres, as per BBD, were evaluated for EE, particle size and drug release characteristics. The optimum formulation was embarked upon using numerical desirability function yielding excellent floatation characteristics along with adequate drug release control. Drug-excipient compatibility studies employing FT-IR, DSC and powder XRD revealed absence of significant interaction among the formulation excipients. The SEM studies on the optimized formulation showed hollow and spherical nature of the prepared microspheres. In vivo X-ray imaging studies in rabbits confirmed the buoyant nature of the hollow microspheres for 8 h in the upper GI tract. In a nutshell, the current investigations report the successful development of gastroretentive floating microspheres for once-a-day administration of ITH.

QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

Development and evaluation of nanoemulsifying preconcentrate of curcumin for colon delivery.

The present study aimed to develop and optimize a nanoemulsifying preconcentrate formulation of curcumin with good emulsification ability and optimal globule size, for controlled targeting in colon. Content of formulation variables, namely, X1 (Peceol), X2 (Cremophor-EL), and X3 (Transcutol HP), were optimized by Box-Behnken design of experiments for its impact on mean globule size (Y1), emulsification time (Y2), and time required for drug release (85%) in phosphate buffer (pH 7.2), t 85% (Y3). Transmission electron micrographs confirmed that there is no coalescence among globules, with size range concordant with the globule size analysis by dynamic light scattering technique (100 nm). 3D plots indicated that concentration of formulation ingredients significantly influences the formulation properties (globule size, emulsification time, and drug release). In vitro release profile (in phosphate buffer; pH 7.2) represents the fact that more than 50% of the drug was released within initial 15 min whereas in vivo release showed limited systemic absorption (C max 200 ng/mL) of curcumin. Stability study ensures the protection of drug in alkaline media which may further confirm the localised delivery of drug to colonic region. Study demonstrated that the nanoemulsifying preconcentrate can be a promising system for the colon specific delivery of curcumin to treat local pathologies.

Development and optimization of polymeric self-emulsifying nanocapsules for localized drug delivery: design of experiment approach.

The purpose of the present study was to formulate polymeric self-emulsifying curcumin nanocapsules with high encapsulation efficiency, good emulsification ability, and optimal globule size for localized targeting in the colon. Formulations were prepared using modified quasiemulsion solvent diffusion method. Concentration of formulation variables, namely, X1 (oil), X2 (polymeric emulsifier), and X3 (adsorbent), was optimized by design of experiments using Box-Behnken design, for its impact on mean globule size (Y1) and encapsulation efficiency (Y2) of the formulation. Polymeric nanocapsules with an average diameter of 100-180 nm and an encapsulation efficiency of 64.85±0.12% were obtained. In vitro studies revealed that formulations released the drug after 5 h lag time corresponding to the time to reach the colonic region. Pronounced localized action was inferred from the plasma concentration profile (C max 200 ng/mL) that depicts limited systemic absorption. Roentgenography study confirms the localized presence of carrier (0-2 h in upper GIT; 2-4 h in small intestine; and 4-24 h in the lower intestine). Optimized formulation showed significantly higher cytotoxicity (IC50 value 20.32 µM) in HT 29 colonic cancer cell line. The present study demonstrates systematic development of polymeric self-emulsifying nanocapsule formulation of curcumin for localized targeting in colon.

Mannosylated chitosan nanoparticles for delivery of antisense oligonucleotides for macrophage targeting.

The therapeutic potential of antisense oligonucleotides (ASODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study focuses on designing mannosylated low molecular weight (LMW) chitosan nanoconstructs for safe ODNs delivery by macrophage targeting. Mannose groups were coupled with LMW chitosan and characterized spectroscopically. Mannosylated chitosan ODN nanoparticles (MCHODN NPs) were formulated by self-assembled method using various N/P ratio (moles of amine groups of MCH to phosphate moieties of ODNs) and characterized for gel retardation assay, physicochemical characteristics, cytotoxicity and transfection efficiency, and antisense assay. Complete complexation of MCH/ODN was achieved at charge ratio of 1:1 and above. On increasing the N/P ratio of MCH/ODN, particle size of the NPs decreased whereas zeta potential (ZV) increased. MCHODN NPs displayed much higher transfection efficiency into Raw 264.7 cells (bears mannose receptors) than Hela cells and no significant toxicity was observed at all MCH concentrations. Antisense assay revealed that reduction in lipopolysaccharide (LPS) induced serum TNF-α is due to antisense activity of TJU-2755 ODN (sequence complementary to 3'-UTR of TNF-α). These results suggest that MCHODN NPs are acceptable choice to improve transfection efficiency in vitro and in vivo.

Dextran conjugated dendritic nanoconstructs as potential vectors for anti-cancer agent.

The purpose of the present investigation was to evaluate the potential of surface engineered polypropylene imine (PPI) dendrimers as nanoscale drug delivery units for site-specific delivery of a model anti-cancer agent, doxorubicin.hydrochloride (DOX). Dextran conjugated PPI dendrimers were synthesized, characterized and further loaded with DOX. The developed formulation was characterized by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR) and transmission electron microscopic (TEM) studies. Dendrimer formulation was evaluated for in vitro drug release and haemolytic studies under various pH conditions. Cell uptake and cytotoxicity studies were performed on A549 cell lines using MTT cell proliferation assay. In vivo studies were conducted for evaluation of various pharmacokinetic parameters and tissue distribution pattern. In vitro, formulation displayed initial rapid release of the drug followed by rather slow release. Further, the dextran conjugated dendrimer formulation was found to be least haemolytic but more cytotoxic as compared to free drug. Cell uptake studies depicted that the formulation was preferably taken up by the tumor cells when compared to free drug. The conjugation of oxidized polyaldehyde dextran imparts macromolecular nature to the dendritic carrier, consequently the formulation was found to selectively enter highly porous mass of tumor cells at the same time precluding normal tissues. Thus it was concluded that the drug loaded dendrimer formulation would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.

Folate and folate-PEG-PAMAM dendrimers: synthesis, characterization, and targeted anticancer drug delivery potential in tumor bearing mice.

Ligand-mediated targeting of drugs especially in anticancer drug delivery is an effective approach. Dendrimers, due to unique surface topologies, can be a choice in this context. In the present study, PAMAM (polyamidoamine) dendrimers up to fourth generation were synthesized and characterized through infrared (IR), nuclear magnetic resonance (NMR), electrospray ionization (ESI) mass spectrometric, and transmission electron microscopic (TEM) techniques. Primary amines present on the dendritic surface were conjugated through folic acid and folic acid-PEG (poly(ethylene glycol))-NHS (N-hydroxysuccinimide) conjugates. Tumor in mice was induced through the use of KB cell culture. Prepared dendritic conjugates were evaluated for the anticancer drug delivery potential using 5-FU (5-fluorouracil) in tumor-bearing mice. Approximately 31% of 5-FU was loaded in folate-PEG-dendritic conjugates. Results indicated that folate-PEG-dendrimer conjugate was significantly safe and effective in tumor targeting compared to a non-PEGylated formulation. Tailoring of dendrimers via PEG-folic acid reduced hemolytic toxicity, which led to a sustained drug release pattern as well as highest accumulation in the tumor area.

Tumour and dendrimers: a review on drug delivery aspects.

Tumour is a morbid state, characterized by spontaneous outgrowth of an abnormal mass of cells. The evolution of tumours is random, disorganized, a condition of numerous mutations. The properties are biased and incompletely comprehended. It is a malignant or benign condition that encompasses its own rules of morphogenesis, an immortal state that elucidates different physiology. It is a pathological crisis that still haunts the minds of scientists, physicians and patients, a complete cure of which is still a dream to be realized. The unpredictable microenvironment of cancerous cells in all of its existing forms i.e. leukaemic cells, solid tumours and sarcomas is well documented. This phenomenon expressed by cancerous sites in the body poses various obstacles towards drug efficacy. Thus, it has become necessary to address briefly the issues relating to tumour physiology, its vasculature and angiogenesis. The information could provide insight towards the development of tumour-targeted drug delivery. The salient features regarding these have been discussed.

Ligand based dendritic systems for tumor targeting.

Medications that can selectively target tumors at the same time avoid access of the drug to nontarget areas, employ utilization of homing devices termed as ligands, that can bind to specific epitopes expressed on the surface of the necrotic mass of cells. Molecular signatures for transferrin, Epidermal Growth Factor, Sialic Lewis and folic acid are expressed on the surface of these cells. Dendrimers are nanosized, non-immunogenic, and hyper-branched vehicles that can be efficiently tailored for spatial distribution of bioactives, thereby reducing untoward cytotoxicity on normal cells. These nanoparticulate drug delivery vehicles provide a unique platform that has precisely placed functional groups so that multiple copies of ligands can be attached to it and facilitate targeting to the tumor surface or neo-vascularizing vessels proliferating around these cells. The article reviews the scope of ligand based dendritic system as a prospective for delivery of anti-cancer drugs, via active targeting with interception of minimal side effects.

Dendritic systems in drug delivery applications.

The design of well-defined particulate carrier systems with controlled size, shapes and physicochemical characteristics is becoming a focal point in the field of biomedicine and drug delivery. Dendrimers are one of the emerging technologies of recent times and have served as a unique platform to achieve the development as novel drug delivery scaffolds. Dendrimers may be engineered to meet the specific needs of biologically active agents, which can either be encapsulated within dendrimers or chemically attached to these units. The large number of active functional groups on the surface of dendrimers allows them to be meticulously tailored and to act as nano-scaffolds or nano-containers of various categories of drugs. The architecture of modified dendrimers has posed a challenge to drug delivery, in particular with respect to their in vivo metabolic fate. The drug delivery applications of dendrimers presented in this article provide an insight of their potential and substantiate the major roles for the future of these nanoconstructs.

Investigations on biodistribution of technetium-99m-labeled carbohydrate-coated poly(propylene imine) dendrimers.

The purpose of this work was to study the biodistribution pattern of the fifth generation of poly(propylene imine) dendrimer (PPI-5.0G)-based carbohydrate (mannose and lactose)-coated glycodendrimers in mice so as to explore the potential of these systems as drug carriers. Plain dendrimers were synthesized and coated with carbohydrates following the reported procedures. The formulations were labeled with radioactive technetium (sodium pertechnetate; 99mTcO4-) and characterized for labeling efficiency as well as in vitro and in vivo stability of the labeled complexes. The blood clearance study was performed in female New Zealand rabbits. The periodic in vivo biodistribution profile of the formulations was investigated in female Balb/c mice. The dendrimeric formulations were labeled with 95% labeling efficiency. The labeled complexes were found to be stable in vitro (97% to 98% stability) and in vivo (89% to 94% stability). All the formulations were cleared rapidly from circulation; clearance of mannose-coated poly (propylene imine) dendrimer (M-PPI) and lactose-coated poly(propylene imine) dendrimer (L-PPI) was faster than PPI-5.0G. All the formulations accumulated in liver to a significant extent, but only those with terminal carbohydrate moieties were retained for a longer period. Significant accumulation of PPI-5.0G and M-PPI was observed in kidneys as against very less activity in the case of L-PPI. Rapid clearance of the dendrimers was in accordance with the earlier reports. Higher and prolonged retention of M-PPI and L-PPI in liver was attributed to lectin-carbohydrate interactions. Lesser accumulation of L-PPI in kidneys was suggestive of its lesser excretion. This observation can be explained on the basis of the molecular weight of L-PPI, which was greater than the threshold of glomerular excretion. In general, it was observed that the carbohydrate-coated dendrimers were distributed in liver to a significant extent. This information could serve as a useful platform in designing carbohydrate-coated dendrimers for selective delivery of bioactive agents to liver.

Intracellular macrophage uptake of rifampicin loaded mannosylated dendrimers.

The present study was aimed at developing and exploring the use of mannosylated dendritic architecture for the selective delivery of an anti-tuberculosis drug, rifampicin (RIF) to alveolar macrophages (AM). The mannosylated dendritic architecture was synthesized and characterized by using IR and NMR spectroscopy. RIF was efficiently loaded into mannosylated dendrimer using dissolution method. Various physicochemical and physiological parameters such as UV, SEM, DSC, drug loading, solubilization, pH dependent in-vitro release, hemolytic toxicity, phagocytic AM uptake and cytotoxicity concerning the mannosylated dendrimer were evaluated. RIF loaded mannosylated dendrimer reduced release rate of drug in pH 7.4, hemolytic toxicity and cytotoxicity; whereas enhanced drug release in pH 5.0 and AM uptake was observed. The present novel dendritic system displayed suitability in terms of biocompatibility and site-specific delivery of antitubercular drug RIF.

Stavudine-loaded mannosylated liposomes: in-vitro anti-HIV-I activity, tissue distribution and pharmacokinetics.

Cells of the mononuclear phagocyte system (MPS) are important hosts for human immunodeficiency virus (HIV). Lectin receptors, which act as molecular targets for sugar molecules, are found on the surface of these cells of the MPS. Stavudine-loaded mannosylated liposomal formulations were developed for targeting to HIV-infected cells. The mannose-binding protein concanavalin A was employed as model system for the determination of in-vitro ligand-binding capacity. Antiretroviral activity was determined using MT-2 cell line. Haematological changes, tissue distribution and pharmacokinetic studies of free, liposomal and mannosylated liposomal drug were performed following a bolus intravenous injection in Sprague-Dawley rats. The entrapment efficiency of mannosylated liposomes was found to be 47.2 +/- 1.57%. Protein-carbohydrate interaction has been utilized for the effective delivery of mannosylated formulations. Cellular drug uptake was maximal when mannosylated liposomes were used. MT2 cells treated continuously with uncoated liposomal formulation had p24 levels 8-12 times lower than the level of free drug solution. Further, the mannosylated liposomes have shown p24 levels that were 14-20 and 1.4-2.3 times lower than the level of free drug and uncoated liposomal formulation treatment, respectively. Similar results were observed when infected MT2 cells were treated overnight. Stavudine, either given plain or incorporated in liposomes, led to development of anaemia and leucocytopenia while mannosylated liposomes overcame these drawbacks. These systems maintained a significant level of stavudine in the liver, spleen and lungs up to 12 h and had greater systemic clearance as compared with free drug or the uncoated liposomal formulation. Mannosylated liposomes have shown potential for the site-specific and ligand-directed delivery systems with desired therapeutics and better pharmacological activity.

Elastic liposomes mediated transcutaneous immunization against Hepatitis B.

Transcutaneous immunization presents a major challenge due to poor permeability of antigens through the skin barrier. To overcome this limitation ultradeformable lipid vesicles, the elastic liposomes, could be a better module for transcutaneous delivery of these proteinaceous antigens. In the present investigation Hepatitis B surface antigen (HBsAg)-loaded elastic liposomes were utilized as a mode for enhanced immunity against the antigen. Elastic liposomes were prepared by conventional rotary evaporation method and characterized for various parameters such as vesicles shape and surface morphology, size and size distribution, entrapment efficiency, elasticity, turbidity, stability and in vitro release pattern. Ex vivo cellular uptake and fluorescence studies were also conducted. In vivo studies were performed by measuring the immune response elicited by topically applied HBsAg-loaded elastic liposomes and compared to the intramuscularly administered alum-adsorbed HBsAg solution, topically applied plain HBsAg solution and physical mixture of HBsAg and elastic liposomes. Results indicate that transcutaneous immunization via elastic liposomes induces robust systemic and mucosal antibody response against HBsAg as compared to other formulations. The fluorescence microscopy results suggest prominent skin permeation and biodistribution, demonstrating efficient delivery of antigens to the immunocompetent Langerhans cells (LC) and lymphatics. The elastic liposomal formulation provides higher entrapment efficiency, enhanced penetration and effective immunoadjuvant property justifying its potential for improved vaccine delivery.

Transdermal delivery of a pineal hormone: melatonin via elastic liposomes.

Melatonin (MT) is a good candidate for transdermal delivery considering its short biological half-life, low molecular weight and a variable oral absorption. The objective of this work was to develop a novel formulation of melatonin for its efficient transdermal delivery. Melatonin loaded elastic liposomal formulation was prepared, characterized and the effect of this developed formulation on the in vitro permeation of melatonin across human cadaver skin was investigated, using a locally fabricated Franz diffusion cell. Skin permeation potential of the developed formulation was assessed using confocal laser scanning microscopy (CLSM), which revealed an enhanced permeation of the formulation to the deeper layers of the skin (up to 180 microm) following channel like pathways. Skin permeation profile of melatonin through elastic liposomal formulations was observed and the investigations revealed an enhanced transdermal flux (51.2+/-2.21 microg/cm(2)/h), decreased lag time (1.1h) and an optimum permeability coefficient (15.06+/-0.52 cm/h) for melatonin. The obtained flux was nearly 5 and 12.3 times higher than conventional liposomal and plain drug solution, respectively (P<0.005). Our result suggests the feasibility of elastic liposomal system for transdermal delivery of melatonin thereby eliminating the limitations of long lag time and poor skin permeation associated with the drug.

Dendrimers: novel polymeric nanoarchitectures for solubility enhancement.

Poor solubility and hydrophobicity of drugs/bioactives limit their possible applications in drug delivery and formulation development. Apart from conventional methods of solubility enhancement, there are some novel methods which can be used in solubilization. Dendrimers represent a novel type of polymeric material that has generated much interest in many diverse areas due to their unique structure and properties. Dendrimer-mediated solubility enhancement mainly depends on factors such as generation size, dendrimer concentration, pH, core, temperature, and terminal functionality. Added advantage in solubilization can be achieved considering these factors. Available literature suggests that ionic interaction, hydrogen bonding, and hydrophobic interactions are the possible mechanisms by which a dendrimer exerts its solubilizing property. This review presents various mechanisms and reports relating to solubility enhancement using dendrimers. Also, micellar behavior and future possibilities in relation to solubilization via dendrimers are included.

Lipid microparticles for mucosal immunization against hepatitis B.

Parenteral administration of vaccines often does not lead to optimal or long lasting protection against disease causing organisms particularly those that are inhaled, ingested or sexually transmitted. For optimal mucosal protection induction of immune response via mucosal routes is therefore highly desirable. Double emulsion-solvent evaporation (w/o/w) method best suited for water-soluble bioactives was selected for the preparation of hepatitis B surface antigen (HBsAg) loaded lipid microparticles. Intranasal route was considered for mucosal administration and hence to prepare the delivery system biocompatible and least irritable, soyalecithin (phospholipid) was taken instead of polymer because phosphatidylcholine is the major component of endogenous lung surfactant. The studies performed in present work included antigen characterization, development of lipid microparticles, stability studies of the prepared lipid microparticle formulations, percent mucoadhesion, ex vivo cellular uptake studies and in vivo studies. The general order obtained from in vivo studies for mucosal immune response (IgA) followed the sequence: LMST-HBsAg (IN)>LM-HBsAg (IN)>alum-HBsAg (IN)>LMST-HBsAg (IM)>alum-HBsAg (IM)>or=LM-HBsAg (IM)>plain HBsAg (IN)>plain HBsAg (IM).

Functional polymeric nanoparticles: an efficient and promising tool for active delivery of bioactives.

Nanotechnology is a multidisciplinary field and has achieved breakthroughs in bioengineering, molecular biology, diagnostics, and therapeutics. A recent advance in nanotechnology is the development of a functional nanosystem by incorporation, adsorption, or covalent coupling of polymers, carbohydrates, endogenous substances/ligands, peptides, proteins, nucleic acids, and polysaccharides to the surface of nanoparticles. Functionalization confers a wide array of interesting properties such as stealth characteristics, a bioadhesive property, and that it prevents aggregation of nanoparticles, imparts biostability and solubility, reduces toxicity, and provides site-specific delivery. This makes the nanosystem an intelligent tool for diagnostics, prognostics, and controlled and sustained delivery of protein, peptide, pDNA, and other therapeutic agents to specific targets (tissue, cell, and intracellular). Various types of functional nanosystems, such as carbon nanotubes, quantum dots, polymeric micelles, dendrimers, metallic nanoparticles, and liposomes, are being extensively explored. However, high tissue accumulation of nonbiodegradable nanoparticles has caused toxicity problems and rendered them as not-so-popular therapeutic and diagnostic systems. The toxicity and safety of nonbiodegradable nanoparticles are subject to future research. Polymeric nanoparticles have offered attractive alternative modules due to biocompatibility, nonimmunogenicity, nontoxicity, biodegradability, simple preparation methods, high physical stability, possibility of sustained drug release, and higher probability for surface functionalization. Depending on properties that have been modified, polymeric nanoparticles can be grouped in to four classes, namely, stealth, polysaccharide decorated biomimetic, bioadhesive, and ligand-anchored functional polymeric nanoparticles (f-PNPs). This review explores the ligand-anchored f-PNP as a carrier for active delivery of bioactives, envisaged to date. This review also details the ligands available for conjugation, their method of coupling to nanoparticles, and applications of f-PNPs in anticancer drug delivery, oral delivery, gene delivery, vaccine delivery, and intracellular delivery; site-specific delivery to liver, macrophages, lymphatics, and brain; and miscellaneous applications. This review also addresses formidable challenges encountered, and proposes some future strategies for development of a promising site-specific active delivery system.