Search

Development of a biodegradable nanoplatform poly(lactic-co-glycolic acid) (PLGA) for co-delivery of two drugs is hugely imperative and beneficial in anticancer therapeutics. In this study, co-deliv...

Targeted delivery of therapeutics forestalls the dreadful delocalized effects, drug toxicities and needless immunosuppression. Cancer cells are bounteous with sialic acid and the differential expression of glycosyl transferase, glycosidase and monosaccharide transporter compared to healthy tissues. The current study entails the development and characterisation of sialic acid (SA)-labelled chitosan nanoparticles encapsulating gemcitabine (GEM). Chitosan (CS) was conjugated with SA using coupling reaction and characterised spectroscopically. Furthermore, different concentrations of chitosan and tripolyphosphate (TPP) were optimised to fabricate surface modified chitosan nanoparticles. SA conjugated chitosan nanoparticles encapsulating GEM (SA-CS_GEM NPs) of 232 ± 9.69 nm with narrow distribution (PDI

The proposed study involves delivering drug/bioactive using a single nanoplatform based on poly lactic-co-glycolic acid (PLGA) for better efficacy, synergistic effect, and reduced toxicity. PLGA was conjugated to doxorubicin (D1), and this conjugate was used for encapsulation of naringenin (D2) to develop naringenin loaded PLGA-doxorubicin nanoparticles (PDNG). The PDNG NPs were 165.4 ± 4.27 nm in size, having 0.112 ± 0.035 PDI, with -10.1 ± 2.74 zeta potential. The surface morphology was confirmed through transmission electron microscopy (TEM) and atomic force microscopy (AFM). The in vitro studies revealed that PDNG NPs exhibited selective anticancer potential in breast cancer cells, and induced apoptosis with S-phase inhibition via an increase in intrinsic reactive oxygen species (ROS) and altering the mitochondrial potential. The results also signified the efficient uptake of nanoparticles encapsulated drugs by cells besides elevating the caspase level suggesting programmed cell death induction upon treatment. In vivo studies results revealed better half-life (27.35 ± 1.58 and 11.98 ± 1.21 h for doxorubicin and naringenin) with higher plasma drug concentration. In vivo biodistribution study was also in accordance with the in vitro studies and in line with the in vivo pharmacokinetic. In vivo tumor regression assay portrayed that the formulation PDNG halts the tumor growth and lessen the tumor volume with the stable bodyweight of the mice. Conclusively, the dual delivery approach was beneficial and highly effective against tumor-induced mice.

Anemia is the most common hematological abnormality of chemotherapy, which is responsible for poor clinical outcomes. To overcome this complication, the present study was aimed for developing a Eudragit/polylactic-co-glycolic acid (PLGA) based nanoparticulate system for a model drug paclitaxel (PTX). The study was planned using a simplex lattice mixture design. PTX nanoparticles (PTXNp) were evaluated in vitro for physicochemical properties, hemolytic effects and cytotoxic effects. Further, the nanoparticles were subjected to in vivo screening using rats for hemocompatibility, pharmacokinetic profile, and biodistribution to the vital organs. The PTXNps were 65.77–214.73 nm in size, showed more than 60% sustained drug release in 360 h and caused less than 8% hemolysis. The parameters like red blood cell count, activated partial thromboplastin time (aPTT), prothrombin time (PT) and C3 complement were similar to the negative control. Cytotoxicity results suggested that all the PTXNp demonstrated drug concentration-dependent cytotoxicity. The in vivo pharmacokinetic study concluded that PTXNp formulations had significantly higher blood AUC (93.194.55–163,071.15 h*ng/mL), longer half-lives (5.80–6.35 h) and extended mean residence times (6.05–8.54 h) in comparison to PTX solution (p

Herbal antioxidant like curcumin holds great potential to treat neurodegenerative disease like Alzheimer's disease. However, its therapeutic potency is obstructed due to rapid metabolism, poor solubility, GI susceptibility, enzymatic degradation and lower bioavailability. Thus, the present work aimed to design and optimize curcumin-loaded NLC (CNL) with higher drug entrapment, prolonged release and better stability. CNL was prepared by modified melt emulsification method followed by ultrasonication. The formulation was optimized by 3 factor 3 level Box-Behnken design using solid: liquid lipid, surfactant concentration and ultrasonication time as independent variable while particle size, entrapment efficiency and % drug release as dependant variable. The design suggested 3.092 solid:liquid lipid, 2.131% surfactant and 4.757 min ultrasonication fit best to get the optimized formulation. The size of the optimized CNL was noted 124.37 ± 55.81 nm, which is in the acceptable range for brain delivery. SEM results also comply with this size range (near 150 nm) and demonstrated almost spherical and uniform particles with porous and uneven surface structures. PDI, zeta potential, entrapment efficiency and % drug release were observed as 0.201 ± 0.00, − 17.2 ± 2.35 mV, 93.62 ± 0.68% and 92.73 ± 0.06%, respectively. The NLC demonstrated initial burst release with subsequent prolonged release of drug for 48 h. Weibull kinetic equation with 0.9958 R2, minimum AIC and maximum MSC value was found best fit to explain the release behavior. The β exponent and diffusional coefficient (n) indicated combined release mechanism with Fickian diffusion as drug release mechanism. Formulation was also found stable at different storage condition.

Lower generation PAMAM dendrimers have an immense potential for drug delivery with lower toxicity, but these dendrimers yet need certain basic ameliorations. In this study, the brain delivery potential of the synthesized PAMAM-Lf (lower generation PAMAM and lactoferrin conjugate) loaded with memantine (MEM) was explored and evaluated in vitro and in vivo in the disease-induced mouse model. The developed nanoscaffolds were characterized for size, zeta potential and in vitro release. Increase in the average size from 11.54 ± 0.91 to 131.72 ± 4.73 nm, respectively, was observed for drug-loaded PAMAM (i.e., PAMAM-MEM) and PAMAM-Lf (i.e., MEM-PAMAM-Lf). Release profile of MEM from MEM-PAMAM-Lf was slow and sustained up to 48 h. In vivo biodistribution in the Sprague-Dawley rat model revealed that the brain uptake of MEM-PAMAM-Lf was significantly higher than that of MEM alone. The behavioral response study in the healthy rats did not result in any significant changes. The in vivo study in an AlCl

The diagnosis and treatment of neurological ailments always remain an utmost challenge for research fraternity due to the presence of BBB. The intranasal route appeared as an attractive and alternative route for brain targeting of therapeutics without the intrusion of BBB and GI exposure. This route directly and effectively delivers the therapeutics to different regions of the brain via olfactory and trigeminal nerve pathways. However, shorter drug retention time and mucociliary clearance curtail the efficiency of the intranasal route. The in situ mucoadhesive gel overthrow the limitations of direct nose-to-brain delivery by not only enhancing nasal residence time but also minimizing the mucociliary clearance and enzymatic degradation. This delivery system further improves the nasal absorption as well as bioavailability of drugs in the brain. The in situ mucoadhesive gel is a controlled and sustained release system that facilitates the absorption of various proteins, peptides and other larger lipophilic and hydrophilic moieties. Owing to multiple benefits, in situ gelling system has been widely explored to target the brain via nasal route. However, very few review works are reported which explains the application of in situ nasal gel for brain delivery of CNS acting moieties. Hence, in this piece of work, we have initially discussed the global statistics of neurological disorders reported by WHO and other reputed organizations, nasal anatomy, mechanism and challenges of nose-to-brain drug delivery. The work mainly focused on the use of different stimuli-responsive polymers, specifically thermoresponsive, pH-responsive, and ion triggered systems for the development of an effective and controlled dosage form, i.e., in situ nasal gel for brain targeting of bioactives. We have also highlighted the origin, structure, nature and phase transition behavior of the smart polymers found suitable for nasal administration, including poloxamer, chitosan, EHEC, xyloglucan, Carbopol, gellan gum and DGG along with their application in the treatment of neurological disorders. The article is aimed to gather all the information of the past 10 years related to the development and application of stimuli-responsive in situ nasal gel for brain drug delivery.

Bortezomib (BTZ) is a proteasome inhibitor as approved by US FDA for the treatment of multiple myeloma. It exhibits significant anti-cancer properties, against solid tumors; but lacks aqueous solubility, chemical stability which hinders its successful formulation development. The present study is an attempt to deliver BTZ using N-(2-hydroxypropyl) methacrylamide (HPMA) based copolymeric conjugates and biotinylated PNPs in an effective manner. Study describes a systematic synthetic pathway to synthesize functional polymeric conjugates such as HPMA-Biotin (HP-BT) HPMA-Polylactic acid (HPLA) and HPMA-PLA-Biotin (HPLA-BT) followed by exhaustive characterization both spectroscopically and microscopically. Our strategy yielded polymeric nanoparticles (PNPs) of narrow size range of 199.7 ± 1.32 nm. Release studies were performed at pH 7.4 and 5.6. PNPs were 2-folds less hemolytic (p < 0.0001) than pure drug. BTZ loaded PNPs of HPLA-BT demonstrated significant anti-cancer activity against MCF-7 cells. IC50 value of these PNPs was 56.06 ± 0.12 nM, which was approximately two folds less than BTZ (p < 0.0001). Cellular uptake study confirmed that higher uptake of formulations might be an outcome of biotin surface tethering characteristics that enhanced selectivity and targeting of formulations efficiently. In vivo pharmacokinetics evidenced increased bioavailability (AUC0 t-∞) of DL-HPLA-BT PNPs (drug loaded) than BTZ with an improved half-life. Overall the developed PNPs led to the improved and effective BTZ delivery.

Polymers are one of the most researched materials in different fields of study like engineering, chemistry, biomedicine, etc. Interpenetrating polymer network-based gels are highly versatile as they possess the properties of two or even more type of polymers from which they are formulated. The 3D structure of IPN hydrogels possesses the ability of holding large quantities of water. These network gels show higher strength and are safe and biocompatible which make them useful for a range of biomedical applications. The combination of natural and synthetic polymers in IPN gels further adds to their advantage. The IPN gels are now also prepared from “smart polymers” which can be easily modified in terms of shape and volume and are sensitive to selected stimuli like temperature, pH, pressure, etc. All these make the development and evaluation of IPN gels a key thrust area for research. The present chapter highlights the various biomedical applications of IPN gels.

Selection of a suitable nanocarrier with an ability to sense and respond to the biological signals is the most essential and challenging step toward the development of a promising targeted drug delivery system. The distinct and integrated physicochemical behavior of carbon nanomaterial presents it as a potential carrier system for site-specific delivery of various therapeutically active moieties including anticancer agents, anti-Alzheimer drugs, neuroprotective agents, antiinflammatory agents, and gene delivery. In addition, these are potentially used in tissue engineering and regenerative medicines. Surface functionalization of carbon nanomaterial is one of the indispensable prerequisites to facilitate drug loading, site-specificity, and safety of the carrier system. Recent investigations are evident that surface functionalization with various bioactives, proteins, peptides, and drug substances improve the therapeutic potency and reduce the toxicity of carbon nanomaterials. The current review article highlights carbon nanomaterial and its biomedical application, including surface functionalization via the covalent and noncovalent coupling. In addition, we have also briefly explained the toxicity profile of carbon nanomaterial.

Carbon dioxide plays a vital role during the synthesis and processing (modification) of polymers. This chapter emphasizes recent advancements in polymer modification using SCO2. The SCO2 is a versatile solvent and finds application during polymer production as well as handling. Polymer production using SCO2 includes various polymerization techniques such as homogeneous polymerization, heterogeneous polymerization, precipitation polymerization, suspension polymerization, and emulsion polymerization. Polymer processing using SCO2 highlights different areas manipulating the property of polymers such as its viscosity, plasticization, tendency to form a microcellular foam, and polymer blends. The application of SCO2 in polymer modification emphasize its purification, dyeing, impregnation, and particle production. Overall, SCO2 can be considered as a good supporting medium for modification of polymers.

Carbon dioxide is widely applied in its supercritical state for extraction of bioactive compounds due to its non-toxic and environment-friendly nature. The supercritical fluid extraction is based on the solvation behavior of supercritical fluids, and the extraction efficiency is affected by different factors such as sample preparation, type of solvent, and various extraction parameters such as pressure, temperature, solvent flow rate, extraction time, and use of co-solvent. Furthermore, the supercritical carbon dioxide (SCCO2) extraction system can be used with supercritical fluid fractionation and supercritical fluid chromatography to purify and identify the extracted compounds. SCCO2 extraction can be an ideal alternative for obtaining high-quality catechin extracts from the green tea plant. In this chapter, we have discussed various extraction techniques, especially supercritical fluid for extraction of catechin from green tea using SCCO2 and the effect of various parameters on the extraction process.

Utilizing the diverse features of biocompatible polymers to target drugs into the tumor/s has been a research hotspot since last decade. Such polymeric conjugates of anti-cancer drugs have proven their potential in providing sustained release of drugs with reduced systemic toxicity and improved tumor retention. Polymers like polyethylene glycol (PEG), N-(2-Hydroxypropyl) methacrylamide (HPMA), Polylactic-co-glycolic acid (PLGA), Polyamidoamine (PAMAM), and others remain exploited for their specific as well as shared characteristics in the rational delivery of anti-cancer agents. Variable nano size, attachment with tumor-specific proteins, responsiveness to stimuli and ability to deliver a wide range of molecules like drugs, antibodies and peptides are some of the achievements of polymeric nano-conjugates so far. Many such conjugates have shown potential clinically which has attracted the researchers and promoted further advancements of the technique. Apart from achievements the polymeric conjugates suffer from shortcomings like poor drug loading and chances of potential chronic-systemic toxicities. The review highlights key findings of research in recent time and advancements taking place in the field of polymeric conjugates of anti-cancer drugs along with the limitations. We have also emphasized on newer and relatively less explored applications of tumor-targeted polymeric conjugates which can add new dimensions to this technique.

Diabetes associated oxidative stress and impaired cholinergic neurotransmission causes cognitive deficits. Although phloridzin shows antioxidant- and insulin sensitizing-activities, its ameliorative potential in diabetes-induced memory dysfunction remains unexplored. In the present study, type 2 diabetes (T2D) was induced by streptozotocin (35 mg/kg, intraperitoneal) in rats on ad libitum high-fat diet. Diabetic animals were treated orally with phloridzin (10 and 20 mg/kg) for four weeks. Memory functions were evaluated by passive avoidance test (PAT) and novel object recognition (NOR) test. Brains of rats were subjected to biochemical analysis of glutathione (GSH), brain-derived neurotrophic factor (BDNF), malonaldehyde (MDA) and acetylcholinesterase (AChE). Role of cholinergic system in the effects of phloridzin was evaluated by scopolamine pre-treatment in behavioral studies. While diabetic rats showed a significant decrease in step through latency in PAT, and exploration time and discrimination index in NOR test; a substantial increase in all parameters was observed following phloridzin treatment. Phloridzin reversed abnormal levels of GSH, BDNF, MDA and AChE in the brain of diabetic animals. Moreover, in silico molecular docking study revealed that phloridzin acts as a potent agonist at M1 receptor as compared to acetylcholine. Viewed collectively, reversal of T2D-induced memory impairment by phloridzin might be attributed to upregulation of neurotrophic factors, reduced oxidative stress and increased cholinergic signaling in the brain. Therefore, phloridzin may be a promising molecule in the management of cognitive impairment comorbid with T2D.

In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease.

The effect of Ca2+ ion cross-linker on acryalamide grafted carboxymethyl xanthan gum (CMXG-g-PAAm) on the drug release was investigated. Previously, CMXG was synthesized from XG and further grafted to CMXG-g-PAAm to retard the drug release. Once the CaCl2 solution is added to CMXG-g-PAAm, Ca2+ considerably affected the drug release mechanism mainly by diffusion and erosion. In order to validate the grafted polymer, tablets were prepared using wet granulation and dry granulation methods It has been noticed that the tablets prepared by wet granulation successfully controls the release of the drug over an extended period of time. Moreover, the release profile was aligned to Korsmeyer-Peppas equation and exhibited the drug transport mechanism via diffusion and erosion.

NLC is a next-generation lipid nanocarrier, which holds many advantages over other colloidal lipid carrier systems like higher drug loading, better and controlled release and enhanced stability. Owing to the unique structural composition, i.e. crystallized solid and liquid lipid blend, it offers excellent biocompatibility and higher permeation across physiological membranes like BBB. Moreover, the surface of NLC can easily be modified with target-specific ligands, proteins, peptides, etc. which makes it a potential candidate for brain targeting of CNS acting drugs. NLC has found various applications for the treatment of various CNS disorders including Alzheimer’s disease, Parkinson’s disease, schizophrenia, epilepsy, migraine, cerebral ischemia, etc. Among these, the application of NLC towards the treatment of AD has been well-explored in the past two decades. In this piece of work, we have discussed the types of NLC, its composition, fabrication techniques, characterization, stability profile and application in the treatment of AD.

Vincristine is a naturally occurring anticancer drug with a specific mechanism of action, given intravenously/bolus to treat various types of cancers, including breast cancer. The present studies explored the potential of thermosensitive injectable nanogel of vincristine loaded nanoparticles. In situ gel was chosen as the delivery system because it restricts the unwanted exposure in blood and other healthy tissues, thus eliminate hemolytic side effects of the drug and offer easy administration in vivo. Furthermore, non-biodegradable and cytocompatible polymeric Eudragit RSPO nanoparticles are proposed as ideal candidates for biomedical usage. The method of preparation includes two major steps—the first formation of vincristine nanoparticles with positively charged Eudragit RSPO. In the second step, these nanoparticles were suspended into a thermosensitive gel base to act as an in situ nanogel. Characterization parameters performed are size, surface charge, vincristine sulfate release behavior and mechanism, polymer-drug interaction, and encapsulation efficiency. In situ nanogel was also evaluated for gelling time, drug release, hemocompatibility and cytotoxic activity in breast cancer MCF-7 cell lines. The magnitude of size ( Furthermore, VS loaded in situ nanogels possessed less hemolytic activity than the pure drug. Hence, it can be concluded that thermo-receptive in situ nanogel of vincristine can be used to treat breast cancer cells with less hemolytic activity. Further in vivo studies are in progress to establish the effectiveness.

In the present work, an unreported graft copolymer of carboxymethyl xanthan gum and acrylamide has been synthesised by free radical polymerisation in a nitrogen atmosphere using ammonium persulphate as an initiator. The optimum reaction conditions adopted for affording maximum percentage of grafting including its grafting efficiency were obtained by varying the concentration of carboxymethyl xanthan gum from 4 to 24 g dm(-3); ammonium persulphate from 5×10(-4) to 30×10(-4)mol dm(-3); acrylamide from 0.4 to 1.2 mol dm(-3); reaction temperature from 55 to 75°C and reaction time from 30 to 90 min. The synthesised graft copolymer has been characterised by (1)H NMR, FTIR spectroscopy, X-ray diffraction measurement, thermal analysis, viscosity measurement and scanning electron microscopy. However, grafting of acrylamide onto carboxymethyl xanthan gum backbone enhanced its thermal stability. This graft copolymer might be well exploited globally as a potential carrier for drug delivery system.

Poor aqueous solubility of anticancer drug bortezomib (BTZ) still remains a major challenge in the development of a successful formulation. The dendrimeric platform can provide a better opportunity to deliver BTZ with improved solubility. BTZ encapsulated in PEGylated PAMAM dendrimers (BTZ-PEG-PAMAM) was characterized and evaluated comparatively with encapsulated and conjugated dendritic formulations. The particle size of BTZ-PEG-PAMAM was 188.6 ± 4.17 nm, with entrapment efficiency of 78.61 ± 2.91% and drug loading of 39.30 ± 1.98%. The aqueous solubility of BTZ in PAMAM-PEG conjugate was enhanced by 68.11 folds in comparison to pure drug. In vitro drug release profile was found to be sustained up to 72 h. A comparative colorimetric MTT assay against A549 and MCF-7 cancer cells resulted in maximum efficacy from BTZ-PEG-PAMAM with IC50 value 333.14 ± 15.42 and 152.60 ± 24.56 nM, respectively. Significantly higher cellular internalization was observed in FITC tagged BTZ-PEG-PAMAM. In vivo pharmacokinetic study performed on Sprague Dawley rats resulted in 8.63 folds increase in bioavailability for BTZ-PEG-PAMAM than pure drug. Pharmacokinetic parameters of BTZ-PEG-PAMAM were better and improved over BTZ and other dendritic formulations. In conclusion, the prepared formulation of BTZ-PEG-PAMAM has given significant outcome and this strategy may be further explored for better delivery of BTZ in future.

Currently, there is no treatment strategy which can reverse the process of neuro-degeneration in progression of Alzheimer's disease (AD). Practically, it is desired to achieve and maintain high therapeutic doses in the brain, but it is hard due to selective permeability of the blood-brain barrier (BBB). In the present study, lactoferrin (Lf) was conjugated to polyamidoamine generation 3.0 (PAMAM G3.0) dendrimers for the effective delivery of rivastigmine (RIV) to the brain. Conjugation of PAMAM G3.0 with lactoferrin was confirmed by FT-IR, 1H NMR, and 2D-NMR spectroscopy as well as AFM techniques. Further, RIV was loaded into PAMAM G3.0 and PAMAM-Lf conjugates. RP-HPLC was used to quantify the drug loading and release as well. Spectroscopic analysis confirmed PAMAM-Lf conjugation, the size of the conjugate was 100.04 ± 3.1 nm, and after RIV loading, the size was increased up to 216.13 ± 2.3 nm. Atomic force microscopic results revealed that the root-mean-square roughness ( Rq) and surface roughness ( Ra) were 6.31 and 5.27 nm, respectively, along with other parameters, Skewness and Kurtosis, which were 0.522 and 2.50, respectively. In vitro drug release from the PAMAM-Lf-RIV conjugate was sustained up to more than 100 h, and that of naive RIV was quite rapid (approxmately 99% release was observed in 8 h). Ex vivo hemotoxicity of the PAMAM-Lf-RIV conjugate was almost 9.8-fold lesser than the PAMAM G3.0 ( p < 0.0001), 7.77 times that of PAMAM-enc-RIV and 5 times that of naive RIV ( p < 0.0001), respectively. The in vivo targeting potency of the conjugate was investigated in a rat model. Bioavailability of the RIV was enhanced 7.87 times compared to RIV along with improved pharmacokinetic parameters. Brain uptake of the drug was improved when treated with PAMAM-Lf-RIV over the RIV and PAMAM-enc-RIV, almost 8 and 4.2 times, respectively, after 4 h of the administration. Additionally, the behavioral studies revealed that PAMAM-Lf-RIV significantly enhanced the overall locomotor activity with higher ambulations over the pure drug and PAMAM-enc-RIV formulation. The outcome of the novel object recognition test was an indirect evidence of memory improvement. Conclusively, the development and characterization of PAMAM-Lf-RIV resulted in improved brain uptake and brain bioavailability with boosted memory, which can be beneficial in the treatment of Alzheimer's.

Protein and peptide delivery by the use of stimuli triggered polymers remains to be the area of interest among the scientist and innovators. In-situ forming gel for the parenteral route in the form of hydrogel and implants are being utilized for various biomedical applications. The formulation of gel depends upon factors such as temperature modulation, pH changes, the presence of ions and ultra-violet irradiation, from which drug is released in a sustained and controlled manner. Among various stimuli triggered factors, thermoresponsive is the most potential one for the delivery of protein and peptides. Poly(ethylene glycol) (PEG) based copolymers play a crucial role as a biomedical material for biomedical applications, because of its biocompatibility, biodegradability, thermosensitivity and easy controlled characters. This review, stresses on the physicochemical property, stability and compositions prospects of smart thermoresponsive polymer specifically, PEG/Poly(N-isopropylacrylamide) (PNIPAAm) based thermoresponsive injectable hydrogels, recently utilized for biomedical applications. PEG-PNIPAAm based hydrogel exhibits good gelling mechanical strength and minimizes the initial burst effect of the drug. In addition, upon changing the composition and proportion of the copolymer molecular weight and ratio, the gelling time can be reduced to a great extent providing better sol-gel transition. The hydrogel formed by the same is able to release the drug over a long duration of time, meanwhile is also biocompatible and biodegradable. Manuscript will give the new researchers an idea about the potential and benefits of PNIPAAm based thermoresponsive hydrogels for the biomedical application.

To establish a platform for the possibility of effective and safe delivery of Temozolomide (TMZ) to brain via surface engineered (polyamidoamine) PAMAM dendrimer for the treatment of glioblastoma. The present study aims to investigate the efficacy of PAMAM-chitosan conjugate based TMZ nanoformulation (PCT) against gliomas in vitro as well as in vivo. The prepared nanoconjugated formulation was characterized by 1H NMR, FT-IR spectroscopy and for surface morphological parameters. The reported approach was also designed in such a way to ensure toxicity before in vivo delivery through conducting the hemolytic study. Surface morphology was found as per nanoformulation via size, pdi and zeta potential measurement. PCT was more efficacious in terms of IC50 values compared to pure TMZ against U-251 and T-98G glioma cell lines. The in vivo pharmacokinetic parameters proved sustained release fashion such as half-life (t1/2) of 22.74 h (PCT) rather than15.35 h (TMZ) only. Higher concentration was found in heart than brain in bio-distribution studies. This study exhibits the potential applicability of dendrimer and CS in improving the anticancer activity and delivery of TMZ to brain. The attractive ex vivo cytotoxicity against two glioma cell lines; U-251 and T-98G and phase solubility studies of TMZ revealed remarkable results. In vivo studies of prepared nanoformulation were significant and promising that explored the double concentration of TMZ in brain due to surface functionality of dendrimer. The reported work is novel and non- obvious as none of such approaches using chitosan anchored dendrimer for TMZ delivery has been reported earlier.

Primaquine phosphate (PQ) is mainly used as a radical cure therapy to eradicate relapse of malaria at the liver stage, which is particularly caused by P. falciparum and P. vivax. In the present study, PQ-loaded galactosylated gelatin nanoparticles (Gel–LA–PQ–NPs) were formulated using a one-step desolvation technique. The mean particle size of Gel–LA–PQ–NPs was found to be 93.48 ± 6.36 nm with a zeta potential of 4.80 ± 0.20 mV having 69.90 ± 1.53% encapsulation efficiency. Electron microscopy demonstrated that the NPs were spherical in shape and uniformly distributed without any cluster formation. The in vitro release of PQ from Gel–LA–PQ–NPs has been facilitated in sustained manner, and the release was three times slower than the naive drug. The prepared nanoparticles (Gel–LA–PQ–NPs) were significantly (p < 0.0001) less hemolytic than the pure drug PQ. The hematological ex vivo study further supported that the developed Gel–LA–PQ–NPs were safer than PQ. The in vitro antiplasmodium assay revealed that th...

The current review emphasizes on the herbal bioenhancers which themselves do not possess inherent pharmacological activity of their own but when co-administered with Active Pharmaceutical Ingredients (API), enhances their bioavailability and efficacy. Herbal bioenhancers play a crucial role in enhancing the bioavailability and bioefficacy of different classes of drugs, such as antihypertensives, anticancer, antiviral, antitubercular and antifungal drugs at low doses. This paper highlights various natural compounds that can be utilized as an efficient bioenhancer. Several herbal compounds including piperine, quercetin, genistein, naringin, sinomenine, curcumin, and glycyrrhizin have demonstrated capability to improve the pharmacokinetic parameters of several potent API. This article also focuses on various United States patents on herbal bioenhancers, which has proved to be beneficial in improving oral absorption of nutraceuticals like vitamins, minerals, amino acids and certain herbal compounds. The present paper also describes proposed mechanism of action, which mainly includes absorption process, drug metabolism, and action on drug target. The herbal bioenhancers are easily available, safe, free from side effects, minimizes drug toxicity, shortens the duration of treatment, lowers the drug resistance problems and minimizes the cost of treatment. Inspite of the fact that herbal bioenhancers provide an innovative concept for enhancing the bioavailability of several potent drugs, there are numerous bioenhancers of herbal origin that are yet to be explored in several vital areas. These bioenhancers must also be implied to enhance the bioavailability and bioefficacy through routes other than the oral route of drug delivery. There is a vast array of unexploited plants which can be investigated for their drug bioenhancing potency. The toxicity profiles of these herbal bioenhancers must not be overlooked. Researches must be carried out to solve these issues and to deliver a safe and effective dose of drugs to attain desired pharmacological response.

Objectives This study aims to develop novel carrier system incorporating luteolin, a poorly soluble biologically active plant active. Methods We investigated a lipid-based drug delivery system to enhance dissolution and absorption profile of luteolin. Luteolin was complexed with phospholipids, and the preparation was characterized. The formulation was evaluated for physicochemical properties, in-vitro solubility or release studies. In vivo anti-inflammatory action of luteolin and its phospholipid complex was evaluated by using carrageenan and 12-O-tetradecanoylphorbol-13-acetate as inducers. Key findings The prepared luteolin–phospholipid complex (LPC) showed drug loading of about 72.64% with average particle size of 152.6 nm. The Fourier transform infrared spectroscopy and thermal studies confirm formation of complex. The solubility of luteolin as LPC was about 2.5 times higher than the solubility of pure luteolin in water. In the diffusion study, LPC showed 95.12% of drug release at the end of 2 h. Animal studies demonstrated significant differences in response of LPC and luteolin. Conclusion LPC was successfully prepared by optimizing the process parameters. The resultant delivery system improved bioavailability and efficacy of luteolin and in the future may become an efficient tool for administration of luteolin.

Objectives In this study, we have used melphalan (ML) as a model drug, used extensively for the treatment of breast cancer. Due to its remarkable haemolytic activity, clinical application of this drug is limited. Methods We incorporated the two synthesized PEGylated melphalan conjugates, viz. MLPEG 2000 and MLPEG 5000, separately into the medium molecular weight chitosan (CS)-based smart thermoreversible in-situ forming injectable hydrogel. Prepared hydrogels were evaluated for gelation time, rheological behaviour, drug release and stability. Key findings Although PEGylated melphalan shows significant increase in aqueous solubility and decrease in haemolytic activity, it was loaded to hydrogel to improve dose frequency and local effect. Hydrogel comprising CS (3.22%, w/v) and glycerophosphate disodium salt (GP) (16%, w/v) showed consistent gelation time and retard the release of drug without compromising its stability. To underline the role of GP, conjugates were loaded into CS solution with and without the GP. Remarkably, absence of GP results in rapid initial burst with nearly complete drug release within 50 h, while addition of GP exhibited drug release up to 100 h. Conclusions Thus, this study highlighted the role of CS/GP thermoreversible injectable hydrogel for successful loading of PEGylated melphalan.

Calcipotriol is a very efficient drug used in the treatment of psoriasis. In present work a novel, hasty, effortless and cost-effective Reversed -Phase High-Performance Thin-Layer Chromatography (RP-HPTLC) technique has been developed and subsequently validated for quantitative assessment of calcipotriol in bulk and in ointment. Optimized chromatographic condition was employed to accomplish separation on a Phenomenex Luna C18 column (250mm X 4.6 mm in diameter) with typical particle size of 5µ column employing Shimadzu HPLC system. Mobile phase constituting of methanol: water (80:20, v/v) was pumped during the chromatographic separation at 1 mL/min flow rate and detection was made by ultraviolet-visible detector at 264 nm. The method was validated for linearity, precision, robustness, accuracy, limit of detection and limit of quantification as per guidelines of International conference on Harmonization (ICH). The method resulted into sharp and well resolved peak for Calcipotriol at 8.2 min retention time. Method was also found to be linear (regression coefficient: 0.999), accurate (average recovery: 100%), precise and robust. Thus the developed analytical method is acceptable for identification and quantitative estimation of calcipotriol in bulk formulation and ointment formulation.

Several methods and techniques are potentially useful for the preparation of microparticles in the field of controlled drug delivery. The type and the size of the microparticles, the entrapment, release characteristics and stability of drug in microparticles in the formulations are dependent on the method used. One of the most common methods of preparing microparticles is the single emulsion technique. Poorly soluble, lipophilic drugs are successfully retained within the microparticles prepared by this method. However, the encapsulation of highly water soluble compounds including protein and peptides presents formidable challenges to the researchers. The successful encapsulation of such compounds requires high drug loading in the microparticles, prevention of protein and peptide degradation by the encapsulation method involved and predictable release, both rate and extent, of the drug compound from the microparticles. The above mentioned problems can be overcome by using the double emulsion technique, alternatively called as multiple emulsion technique. Aiming to achieve this various techniques have been examined to prepare stable formulations utilizing w/o/w, s/o/w, w/o/o, and s/o/o type double emulsion methods. This article reviews the current state of the art in double emulsion based technologies for the preparation of microparticles including the investigation of various classes of substances that are pharmaceutically and biopharmaceutically active.

The objective of the current study was to develop and optimize an orodispersible tablet formulation of montelukast sodium which is an effective drug in the treatment of asthma and allergic disorders. Montelukast sodium is the drug used in treatment of ashthmatic and allergicrhinitis; it is selective leukotrienesreceptor antagonist. Orodispersible tablet is rapid dissolving or disintegrates without water within a few minutes in the oral cavity which may produce rapid onset of action due to the action of superdisintegrants. The orodispersible tablet were prepared by direct compression method using superdisintegrant agent such as croscarmilose sodium, crosspovidone and sodium starch glycolate. Six formulations of superdisintegrants having different concentration were prepared. After examine the angle of repose, bulk density, tapped density, Compressibility index and Hausner's ratio of powder blend the results were found to be within prescribed limits and indicated good flowing property. The tablets were evaluated for hardness, drug content, friability, weight variation, wetting time and in vitro disintegration time and were found to be satisfactory. Among the formulations tablets of batch F3 and F6 containing co-processed disintegrating agents like croscarmilose: sodium starch glycolate (1: 2) and crospovidone: croscarmiloss sodium (1: 2) respectively showed superior organoleptic properties along with excellent in-vitro disintegration time and drug release as compare to other formulations. Hence crospovidone is recommended as suitable disintegrant for the preparation of direct compression mouth dissolving tablets of Montelukast sodium.

Alzheimer's disease, is a somatic disease that affects the brain. It is a progressive disease that destroys memory and other important mental functions. During this disease, accumulation of cerebral extracellular amyloid, which is mostly composed of accumulated amyloid-β (Ab) peptide as well as the accumulation of intracellular neurofibrillary tangles, appears to start up. This results in the loss of connection between nerve cell, and lead to the degeneration of neurons and finally death of brain tissue. Also due to the deficiency of some important chemical messenger in the brain, the signal transmission gets ultimately, affected in the body. The main objective of this study was to prepare the optimized formula of a VCO based emulsion containing Tween 20 as the surfactant for treatment of Alzheimer's disease which may help to increase the cholesterol level in the brain and to destroy the β amyloid plaque as a result of which the level of chemical messenger will increase in the brain. This study is further aimed to analyze, concentration of drug reaching into the brain and to study its effect in destroying β amyloid plaque.

Inspite of several dosage forms available in the market for effective localized action, the lozenges finds a special importance, as they are the best dosage forms for formulating large dose medicaments. The anatomy of mouth and cheek favors easy absorption of drug, reducing the systemic absorption thus ensuring a better patient compliance especially for pediatrics and geriatrics. Ascorbic acid mechanism of action suites this type of formulation and easily absorbed in oral cavity. Preformulation studies are primarily done to investigate the physicochemical properties of drug and to establish its compatibility with other excipients. Ascorbic acid was mixed with all excipients, used in the formulation in different. The formulated lozenges were evaluated for physical parameters and the results complied with the pharmacopoeiallimits.ascorbic acid hard candy lozenges were prepared by heat fusion method using sugar as a base. The usage of corn syrup in the formulation made the lozenges transparent and smooth, which helped in improving the elegancy of formulation. The controlled release of medicament from Lozenges was achieved by using polymers like methyl cellulose, locust bean gum, HPMC, K4M and xanthan gum. The prepared lozenges were subjected to physico-chemical as well as in vitro drug release study. Among all the formulations of hard candy lozenges FL1 showed good stability.

With emergence of new technology and concept, self-poring osmotic tablets were developed in order to reduce the complications and problems associated with micro drilling and laser drilling in osmotic tablet. This research describes a very simple and cheap method of developing self-poring osmotic tablet that deliver Diltiazem HCl in a controlled rate for prolonged duration. For this purpose 5 formulations of osmotictablets were prepared through wet granulation technique in which different concentration of sodium lauryl sulphate (SLS) were used as pore forming agent in coating solution. In tablet core also varied concentration of sorbitol as osmogens, guar gum and HPMC were encorporated, which forms gel like matrix through which drug releases at zero order. Through optimization out of 5 formulations, F3 (C2) formulation was selected as best. From result of invitro drug release study it was clear that more concentration of pore former and osmogens releases drug in short time while less concentration takes more time for drug release. Therefore, it is necessary to use SLS, polymer and osmogens in balance concentration for getting optimum control release at zero order upto 24 hrs. Self-poring Osmotic tablets hold promising potential for increasing drug efficacy and reducing dosing frequency with minimal side effects also provides an economic means of developing controlled release dosage forms.

Mouth dissolving oral films are useful in patients such as paediatric, geriatric, bedridden or developmentally disabled who face difficulty in swallowing conventional tablets or capsules and liquid orals or syrups leading to ineffective therapy. Mouthdissolving films have been played an important role in the current pharmaceutical research. They have convenience and ease of use over other dosage forms such as orally disintegrating tablets and immediate release tablets. Mouth dissolving films are oral solid dosage form that disintegrate and dissolve within a minute when placed in mouth without taking water or chewing. Risperidone is effective for treating the positive and negative symptoms of schizophrenia compared to first generation antipsychotics. But oral administration of Risperidone has drawbacks such as hepatic first pass metabolism which is overcome by means of mouth dissolving film. In the present research, mouthdissolving films of riseperidone were developed using low viscosity grades of HPMC K15 and sorbitol polymers and propylene glycol as plasticizer and purified water as solvent followed by solvent casting method. All films prepared were smooth and elegant in appearance and showed no visible cracks; were uniform in thickness, weight and drug content.

The aim of present research was to report the buccoadhesive tablet of itraconazole to provide localized delivery of drug for the treatment of oral thrush and maintain the drug concentration in the mouth for prolonged period of time thereby improving the oral bioavailability of drug. Buccoadhesive tablet is a sustained release of itraconazole for easy permeation across buccal mucosa and provide a local delivery concentration that may or may not be sufficient to maintain MIC to kill the microorganism. Solid dispersion of itraconazole was prepared by solvent evaporation technique using silica gel act as adsorbent and drug was soluble in chloroform to obtain a slurry or uniform mixture. The buccoadhesive tablet was prepared by direct compression method using different polymers such as Carbopol(C934P), HPMC K4M, Eudragit E100. Five formulations of different concentrations were prepared. Itraconazole strength were kept constant at 30mg and target was fixed at 120mg. After examine the moisture content, bulk density, tapped density, Angle of repose of powder blend get the result were found to be prescribed limit and indicated good flow property. Then the tablets were evaluated for hardness, thickness, weight variation, drug content, friability, swelling index, In-vitro drug release.

Monteleukast sodium is most commonly used in treatment of Asthma. It mainly prevents leukotriene mediated effect associated with asthama. Dispersible tablet are film coated or uncoated tablet that can be dispersed in liquid medium before administration, giving a homogenous dispersion. Dispersible tablet were prepared by using a direct compression method employing super disintegrating agentsuch as cross povidone, cross carmellose sodium and sodium starch glycolate, the tablet were preparedusing various diluents like MCC and lactose. Magnesium stearate and talc is used as a lubricant and glidant. Pre-compression parameter such as angle of repose, bulk density, tapped density, carrs index, hausner ratio carried out to study the flow properties of powder to achieve uniformity of tablet. The prepared tablet were evaluated for hardness, thickness, weight variation friablitity, % drug content, disintegration time and other parameter such as wetting time were also evaluated.

The candesartan cilexetil floating matrix drug delivery system was design to prolong the gastric residence time and improve its bioavailability. The candesartan cilexetil floating matrix tablet was prepared by using direct compression technique. Various natural polymer such as xanthan gum, guar gum as well as synthetic polymer such as hydroxypropyl methyl cellulose used in combination along with other standard excipients. Here, sodium bicarbonate acts as gas-generating agent. The granules undergoes through pre and post compression studies. The tablet evaluated by using various evaluating parameter viz, hardness, friability, weight variation, content uniformity, floating capacity and in vitro drug release studies.

Azithromycin is used for the treatment of bacterial infection, mainly used in middle ear infection, typhoid, sinusitis, bronchitis in urinary tract infection and venereal disease. The present study aimed to develop dry or oral reconstitutable suspension to minimize the solubility problem of the drug. It shows the adequate chemical stability of the drug during the shelf life and it avoids the problem of physical stability and solubility of drug. The study was carried out by preparing the dry powder or granules for oral reconstitutable suspension by using suspending agent sodium CMC and acacia on release profile of the drug. The prepared best formulation (F6) was selected depending on its physiochemical properties. The prepared oral reconstitutable suspension was evaluated for the rheological, viscosity, re-suspendibility and sedimentation volume. The formulation of acacia showed excellent sedimentation volume and good re-dispersibility as compared to other formulation. The study was found that the dry physical mixture method showed good stability of the drug.

Many predefined ways are now a day adopted to interface with biological tissues. One such significant class of biomaterials are hydrogels, which are defined as highly hydrated materials. Hydrogels are designed to absorb a large amount of water or biological fluids due to its three-dimensional, hydrophilic, polymeric network. They closely simulate natural living tissue, more so than any other class of synthetic biomaterials because of their high-water content, porosity, and soft consistency. They are chemically stable but may degrade and gradually disintegrate up to dissolve. Now a day they become more popular because of their unique property of flexibility and biocompatibility. Hydrogels can be produced by both natural and synthetic polymers. These polymers undergo physical and chemical cross-linking to produce hydrogels. Due to their resemblance to the living tissue, they have the immense possibility to use hydrogels in the biomedical field. Some of the well-known use of hydrogels include manufacturing contact lenses, hygiene products, tissue engineering scaffolds, drug delivery system and wound dressings. The current review article deals with information about the hydrogels, their various types, preparation methods along with an evaluation of the same. Also, the present study is performed for the motivation of the graduates towards publication and research. Hence, we have encouraged the graduates to prepare an informative article on the present subject.

Drug induced hemolysis is a frequent complication associated with chemotherapy. It results from interaction of drug with erythrocyte membrane and leads to cell lysis. In recent past, various approaches were made to reduce drug-induced hemolysis, which includes drug polymer conjugation, drug delivery via colloidal carriers and hydrogels, co-administration of botanical agents and modification in molecular chemistry of drug molecules. The basic concept behind these strategies is to protect the red blood cells from membrane damaging effects of drugs. There are several examples of drug polymer conjugate that either are approved by Food and Drug Administration or are under clinical trial for delivering drugs with reduced toxicities. Likewise, colloidal carriers are also used successfully nowadays for the delivery of various chemotherapeutic agents like gemcitabine and amphotericin B with remarkable decrease in their hemolytic activity. Similarly, co-administration of botanical agents with drugs works as secondary system proving protection and strength to erythrocyte membranes. In addition to the above statement, interaction hindrance between RBC and drug molecule by molecular modification plays an important role in reducing hemolysis. This review predominantly describes the above recent approaches explored to achieve the reduced hemolytic activity of drugs especially chemotherapeutic agents.

Ease of administration and painless approach made oral route the most preferred. Poor oral bioavailability is pronounced with the majority of recent active ingredients because of dissolution rate limited absorption. Failure to attain intended therapeutic effect of the poor water soluble drugs by this route led to development of novel drug delivery systems which will fulfill therapeutic needs with minimum dose. Although many formulation approaches like solid dispersions, complexation, pH modifications and lipid based delivery systems finding increased appliance with the apparent increase in absorption of drug. Among lipid based formulations, self-micro emulsifying formulations (droplet size < 100 nm) are evident to improve the oral bioavailability of hydrophobic drugs primarily due to their efficiency in facilitating solubilization and in presenting the hydrophobic drug in solubilized form whereby dissolution process can be circumvented. Various components that are used to formulate these dosage forms like surfactants and lipids contribute to the overall improvement in oral bioavailability via promoting the lymphatic transport; thereby hepatic first pass metabolism can be surmounted. The present article gives exhaustive information on the formulation design and characterization of SMEDDS by which the bioavailability can be improved. In this review article, the various aspects of pharmaceutical SMEDDS where compiled together and target audience are specifically the B. Pharm and M. Pharm students so that their knowledge towards the subject concern can be enhanced and also at the same time can be motivated towards the publication.

Transdermal drug delivery systems (TDDS) are dosage forms involves drug transport to viable epidermal and or dermal tissues of the skin for local therapeutic effect while a main function of drug is transported into the systemic blood circulation. The purpose of this research was to develop a matrix-type transdermal therapeutic system containing drug diclofenac with different ratios of hydrophilic (hydroxyl propyl cellulose) and hydrophobic (ethyl cellulose) polymeric systems polymeric systems by the solvent evaporation technique and by using Glycerol as plasticizer. Different concentrations of oleic acid and isopropyl myristate were used to enhance the transdermal permeation of Diclofenac. To improve characters of transdermal drug delivery system (TDDS) was emerged, which will improve the therapeutic efficacy and safety of drugs by specific sites within the body, thereby reducing both the size and number of doses. The present article reviews the selection of drug candidates and polymers suitable to be formulated as transdermal system, advantages, disadvantages of formulation design and the methods of evaluation. In this review article the various aspects of pharmaceutical transdermal drug delivery system where compiled together and the target audience are specifically the M Pharm and B Pharm students so that their knowledge towards the subject concern can be enhanced and also at the same time can be motivated towards the publications.

Controlled drug delivery is useful because it allows obtaining better drug product, effectiveness, reliability and safety. Hydrogel are one of the upcoming classes of polymer-based controlled release drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogel also show stimuli-responsive changes in their structural network and hence, the drug release. Because of large variations in physiological pH at various body sites in normal as well as pathological conditions, pH-responsive polymeric networks have been extensively studied. This review highlights the use of hydrogel (a class of polymeric systems) in controlled drug delivery, and their application in pH-responsive, drug release. Hydrogel show minimal tendency to adsorb proteins from body fluids because of their low interfacial tension. Further, the ability of molecules of different sizes to diffuse into (drug loading) and out of (drug release) hydrogel allows the possible use of dry or swollen polymeric networks as drug delivery systems for oral, nasal, buccal, rectal, vaginal, ocular and parenteral routes of administration. Hydrogel also terms ‘intelligent gels’ or ‘smart hydrogel’. The smartness of any material is the key to its ability to receive, transmit or process a stimulus, and respond by producing a useful effect. This review highlights the use of hydrogel (a class of polymeric systems) in controlled drug delivery, and their application in stimuli responsive, especially pH-responsive, drug release. In this review article, the various aspects of pharmaceutical microemulsin where compile together and the target audience are specifically the M. pharm and B .pharm student so that their knowledge towards the subject concern can be enhanced and also at the same time can be motivated towards the publication.