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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. • Cognitive deficit in diabetes is linked with oxidative stress, impaired neuroprotection and cholinergic neurotransmission. • Phloridzin is a flavonoid with promising antioxidant and insulin sensitizing actions in type 2 diabetes. • Four weeks treatments with phloridzin significantly reversed cognitive deficit in diabetic rats. • Phloridzin enhanced cholinergic neurotransmission, antioxidant defense and neurotrophic factor in the brain of diabetic rats. • Phloridzin may have therapeutic potential in the management of cognitive impairment associated with diabetes. [ABSTRACT FROM AUTHOR]

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 < 0.05). Overall, the study provides a nanoparticulate drug delivery system to deliver PTX safely and effectively along with reducing the associated hematological adverse effects. [Display omitted] • A simplex lattice mixture design of experiment was used to study the influence of formulation polymers (ERSPO, ERLPO and PLGA) and their respective concentrations on particle size, hemolysis and drug release. • Lastly, the three optimized nanoparticles were evaluated in vitro and in vivo specifically for their pharmacokinetic profile, biodistribution studies, and hemocompatibility studies. • The optimized PTX nanoparticles demonstrated significant hemocompatibility as compared to pure drug solution. • The mean AUC and terminal half-life of PTX upon IV administration of PTXNp was significantly higher than from pure PTX solution. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • Imperfect lattice structure of NLC greatly enhances drug entrapment efficiency. • Drug loaded NLC was prepared by melt-emulsification ultrasonication method. • Effect of solid:liquid lipid, surfactant concentration on formulation was optimized. • Initial burst release with subsequent sustained release of 92.73% drug. • Weibull kinetic exponent showed combined release mechanism with Fickian diffusion. [ABSTRACT FROM AUTHOR]

• Poor aqueous solubility of bortezomib: major drawback in formulation development. • Bortezomib encapsulation in PEGylated PAMAM dendrimers. • Cytotoxicity assay against A549 and MCF-7 cancer cells. • In vivo pharmacokinetic studies co-relating the in vitro results. 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 IC 50 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. [ABSTRACT FROM AUTHOR]

• Synthesis and evaluation of conjugates; HPMA-Biotin, HPMA-PLA, HPMA-PLA-Biotin. • Effect of biotin as a targeting ligand on breast cancer cells. • Two folds reduction in IC 50 values of HPLA-BT PNPs than pure BTZ. • Cellular uptake interactions of PNPs in breast cancer cells. • In vivo data (bioavailability, t1/2, v d) supported in vitro results. 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. IC 50 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 (AUC 0 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. [ABSTRACT FROM AUTHOR]

The field of cancer therapy has witnessed significant strides with the emergence of innovative drug delivery systems and one such promising avenue is solid lipid-based nanoparticle (SLN) technology. This abstract provides a complete overview of current advances in developing SLNs for effective cancer treatment solid lipid nanoparticles (NPs) represent a novel drug delivery platform characterized by their unique composition which includes biocompatible lipids as the main carrier material. This technology addresses challenges related to standard chemotherapy such as low bioavailability limited medicine stability and non-specific targeting. The incorporation of lipids in SLNs ensures enhanced drug encapsulation, protection of therapeutic agents from degradation-controlled release profiles. Recent breakthroughs in SLN technology have focused on optimizing formulation parameters to achieve superior drug loading capacities stability and sustained release kinetics. Advanced fabrication techniques including high-pressure homogenization and microemulsion methods have been pivotal in tailoring SLN properties for specific cancer types and therapeutic agents. Furthermore, SLNs' capacity to passively build up in tumor tissues using increased penetration and retention effects has been harnessed for targeted drug transport. Surface modifications using ligands or antibodies to facilitate active targeting, enhancing medication delivery's selectivity to tumor cells decreasing unwanted effects on normal tissues. This abstract highlights recent preclinical and clinical studies demonstrating the efficacy of SLN-based formulations in enhancing the therapeutic outcomes of various anticancer agents. The versatile nature of SLN technology makes it a viable option for the advancement of personalized and precision cancer therapies, marking a significant stride toward overcoming the limitations of conventional cancer treatments. As research in this domain progresses, the integration of SLNs holds immense potential for revolutionizing tumor treatment strategies., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

This thorough analysis looks critically at how glycosaminoglycan (GAG) supports joint health. It emphasizes the importance of GAG in particular, clarifies the underlying processes linked to joint pain, and assesses the shortcomings of traditional therapy modalities. Additionally, the research delves into several traditional approaches, such as injectable GAG therapy and oral supplements, carefully evaluating the benefits and drawbacks of each. The study then explores novel GAG drug delivery technologies, acknowledging the urgent need for better treatment approaches. The article highlights the potential of hydrogel-based systems, liposomal/micellar carriers, and nanoparticles in addressing current challenges in GAG delivery. These challenges include achieving sustained release, improving bioavailability, facilitating targeted delivery, and reducing safety concerns related to biocompatibility. Examining these elements closely and critically, the review seeks to provide a thorough grasp of the developments, difficulties, and possible breakthroughs in GAG delivery systems. In the end, this thorough investigation will greatly aid in the improvement of joint pain therapies. The results imply that by shielding articular joints from erosive effects, early use of GAG therapy-particularly hyaluronic acid-can reduce joint deterioration associated with arthritis. Even though GAG-based therapies have shown promise in lowering inflammation and increasing joint flexibility, further study is required to improve their effectiveness in treating joint pain, particularly in diseases like osteoarthritis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Red blood cells with sickle cell anemia (SCA) have an irregular shape, and it is a genetic blood condition that can cause several problems and shorten life expectancy. Traditional treatments have focused on symptom management, but recent advancements in drug delivery systems offer promising pathways for targeted therapies. This abstract explores novel approaches to combat SCA through innovative drug delivery systems, gene therapy, and new pharmaceutical interventions. One novel pathway for targeting SCA involves utilizing advanced drug delivery systems to enhance the effectiveness of therapeutic agents. Nanotechnology-based delivery systems, such as nanoparticles and liposomes, offer precise drug targeting, controlled release, and improved bioavailability. These systems can encapsulate anti-sickling agents, like hydroxyurea, and enable their specific delivery to affected cells, reducing side effects and enhancing therapeutic outcomes. Additionally, therapy has become a ground-breaking method of treating SCA. CRISPR/Cas9 technology presents a groundbreaking opportunity to correct the genetic mutation responsible for sickle hemoglobin production. By precisely editing the HBB gene, which encodes the abnormal hemoglobin, researchers aim to restore normal hemoglobin expression, potentially offering a curative treatment for SCA. Furthermore, recent advancements in drug development have led to the discovery of promising candidates targeting specific pathways involved in SCA pathophysiology. Experimental drugs, such as voxelotor and crizanlizumab focus on modifying hemoglobin properties or inhibiting cell adhesion, respectively, thereby preventing sickle cell-related complications and reducing vaso-occlusive crisis frequency., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Due to their potential to enhance therapeutic results and enable targeted drug administration, polymer-drug conjugates that use polyethylene glycol (PEG) as both the polymer and the linker for drug conjugation have attracted much research. This study seeks to investigate recent developments in the design and synthesis of PEG-based polymer-drug conjugates, emphasizing fresh ideas that fill in existing knowledge gaps and satisfy the increasing need for more potent drug delivery methods. Through an extensive review of the existing literature, this study identifies key challenges and proposes innovative strategies for future investigations. The paper presents a comprehensive framework for designing and synthesizing PEG-based polymer-drug conjugates, including rational molecular design, linker selection, conjugation methods, and characterization techniques. To further emphasize the importance and adaptability of PEG-based polymer-drug conjugates, prospective applications are highlighted, including cancer treatment, infectious disorders, and chronic ailments., Competing Interests: Declarations Ethical Approval Not applicable. Consent to Participation All the authors had their consent for participation in the reported study. Consent for Publication All the authors had their consent for the publication of the reported study. Competing Interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer is a global health issue that requires ongoing therapeutic advances. This review provides an overview of recent treatment strategies focusing on novel pathways in cancer therapy. Emerging research has unveiled promising targets that go beyond traditional modalities, offering new avenues for precision medicine and improved patient outcomes. One key area of innovation lies in targeted therapies directed at specific molecular pathways implicated in cancer progression. The identification of novel biomarkers has paved the way for the development of precision medicines tailored to individual patient profiles. Immunotherapy has also revolutionised cancer treatment by using the immune system to identify and remove cancer cells. Moreover, advancements in epigenetic therapies and RNA-based interventions demonstrate unprecedented potential in modulating gene expression and disrupting cancer-specific signalling pathways. We have discussed the pathophysiology of cancer, different immune checkpoint inhibitors, and targeted therapies in signalling therapies. The epigenetic modulators, such as Histone deacetylase (HDACs) inhibitors and DNA methyltransferase (DNMT) inhibitors, were studied. Recent breakthroughs in cancer immunotherapy treatment (CAR-T) cell therapy showcase the potential to enhance the immune response against various cancers; thus, related information was incorporated. Further, RNA-based therapies like RNA interference and mRNA-based vaccines and therapies, combination therapies, and novel therapies were discussed in the present article., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Contextualizing the void of research on inhalant abuse among adolescents as epistemic neglect, in this study, we use mixed-methods action research to understand inhalant abuse in a specific context in the Global South. Focusing on a large metropolitan city in Western India, we surveyed 158 street-involved children and adolescents (110 boys and 48 girls, age range from 5 to 17 years) in a group setting along with follow-up group interviews. Despite finding a high prevalence rate of inhalant abuse, our work suggests an absence of supporting structures and emphasizes the need to revisit our understanding and interpretation of substance-using behavior of street-involved youth. Instead of explaining inhalant-abusing behavior as emerging from pathological deficiencies in individuals or households, we stress the need to critically examine the exploitative environment they are embedded in. In doing so, we join efforts to decolonize conventional ways of understanding "deviant" behavior., (© 2024 Society for Research on Adolescence.)

Anticancer medications as well as additional therapeutic compounds, have poor clinical effectiveness due to their diverse distribution, non-selectivity for malignant cells, and undesirable off-target side effects. As a result, ultrasound-based targeted delivery of therapeutic compounds carried in sophisticated nanocarriers has grown in favor of cancer therapy and control. Nanobubbles are nanoscale bubbles that exhibit unique physiochemical properties in both their inner core and outer shell. Manufacturing nanobubbles primarily aims to enhance therapeutic agents' bioavailability, stability, and targeted delivery. The small size of nanobubbles allows for their extravasation from blood vessels into surrounding tissues and site-specific release through ultrasound targeting. Ultrasound technology is widely utilized for therapy due to its speed, safety, and cost-effectiveness, and micro/nanobubbles, as ultrasound contrast agents, have numerous potential applications in disease treatment. Thus, combining ultrasound applications with NBs has recently demonstrated increased localization of anticancer molecules in tumor tissues with triggered release behavior. Consequently, an effective therapeutic concentration of drugs/genes is achieved in target tumor tissues with ultimately increased therapeutic efficacy and minimal side effects on other non-cancerous tissues. This paper provides a brief overview of the production processes for nanobubbles, along with their key characteristics and potential therapeutic uses., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cancer is a broad term for a set of disorders marked by the development of physically and functionally changed cells that proliferate uncontrollably, infect neighboring tissues, and result in malignant tumours, 'neoplasm'. Cancer remains a difficult disease to treat because of the significant adverse effects and poor pharmacokinetic profile of antineoplastic drugs, despite advancements in our understanding of the features and behavior of tumor cells in recent decades. In this series, the role of natural polymers is prominent as a component of a novel delivery system of anticancer drugs. These natural polymeric drug delivery systems (NPDDS) have many advantages over synthetic polymers like controlled delivery, biodegradability, inexpensive, low toxicity profile, and easily obtainable. These polymers further modify for the targeting of tumour cells. This review discusses and critically analyses the different natural polymers, such as chitosan, cellulose, starch, albumin, dextran, fucoidan, gelatin, etc., in terms of natural ingredient-based polymeric nanocarriers specifically for cancer therapy. It also describes benefits, drawbacks, and opinions and provides insights about the efficacy of NPDDS as well as its future perspectives and tabulated recent patents and cases under clinical trials exploited for cancer treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The temperature-triggered in situ gelling system has been revolutionized by introducing an intelligent polymeric system. Temperature-triggered polymer solutions are initially in a sol state and then undergo a phase transition to form a gel at body temperature due to various parameters like pH, temperature, and so on. These smart polymers offer a number of advantages, including ease of administration, long duration of release of the drug, low administration frequency with good patient compliance, and targeted drug delivery with fewer adverse effects. Polymers such as poly(N-isopropylacrylamide) (PNIPAAm), polyethylene glycol (PEG), poly (N, N'-diethyl acrylamide), and polyoxypropylene (PPO) have been briefly discussed. In addition to various novel Drug Delivery Systems (DDS), the smart temperature-triggered polymeric system has various applications in cancer therapy and many other disease conditions. This review focuses on the principals involved in situ gelling systems using various temperature-triggered polymers for chemotherapeutic purposes, using smart DDS, and their advanced application in cancer therapy, as well as available marketed formulations and recent advances in these thermoresponsive sol-gel transforming systems., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Acetylcholine (ACh) is ubiquitously present in the nervous system and has been involved in the regulation of various brain functions. By modulating synaptic transmission and promoting synaptic plasticity, particularly in the hippocampus and cortex, ACh plays a pivotal role in the regulation of learning and memory. These procognitive actions of ACh are mediated by the neuronal muscarinic and nicotinic cholinergic receptors. The impairment of cholinergic transmission leads to cognitive decline associated with aging and dementia. Therefore, the cholinergic system has been of prime focus when concerned with Alzheimer's disease (AD), the most common cause of dementia. In AD, the extensive destruction of cholinergic neurons occurs by amyloid-β plaques and tau protein-rich neurofibrillary tangles. Amyloid-β also blocks cholinergic receptors and obstructs neuronal signaling. This makes the central cholinergic system an important target for the development of drugs for AD. In fact, centrally acting cholinesterase inhibitors like donepezil and rivastigmine are approved for the treatment of AD, although the outcome is not satisfactory. Therefore, identification of specific subtypes of cholinergic receptors involved in the pathogenesis of AD is essential to develop future drugs. Also, the identification of endogenous rescue mechanisms to the cholinergic system can pave the way for new drug development. In this article, we discussed the neuroanatomy of the central cholinergic system. Further, various subtypes of muscarinic and nicotinic receptors involved in the cognition and pathophysiology of AD are described in detail. The article also reviewed primary neurotransmitters that regulate cognitive processes by modulating basal forebrain cholinergic projection neurons., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Most cancer patients rarely benefit from monodrug therapy because of both cancer complexity and tumor environment. One of the main reasons for this failure is insufficient accumulation of the optimal dose at the tumorous site. Our investigation implies a promising strategy to engineer prodrug nanoparticles (NPs) of bortezomib (BTZ) and selenium (Se) using sialic acid (SAL) as a ligand to improve breast cancer therapy. BTZ was conjugated with SAL and HPMA ( N -2-hydroxypropyl methacrylamide) to prepare a prodrug conjugate; BTZ-SAL-HPMA (BSAL-HP) and then fabricated into prodrug NPs with Se (Se&#95;BSAL-HP prodrug NPs). The self-assembly of prodrug NPs functionalized with Se showed size (204.13 ± 0.02 nm) and zeta potential (-31.0 ± 0.11 mV) in dynamic light scattering (DLS) experiments and spherical shape in TEM and SEM analysis. Good stability and low pH drug release profile were characterized by Se&#95;BSAL-HP prodrug NPs. The tumor-selective boronate-ester-based prodrug NPs of BTZ in combination with Se endowed a synergistic effect against cancer cells. Compared to prodrug conjugate, Se&#95;BSAL-HP prodrug NPs exhibited higher cell cytotoxicity and enhanced cellular internalization with significant changes in mitochondria membrane potential (MMP). Elevated apoptosis was observed in the (G2/M) phase of the cell cycle for Se&#95;BSAL-HP prodrug NPs (2.7-fold) higher than BTZ. In vivo studies were performed on Sprague-Dawley rats and resulted in positive trends. The increased therapeutic activity of Se&#95;BSAL-HP prodrug NPs inhibited primary tumor growth and showed 43.05 fold decrease in tumor volume than the control in 4T1 tumor bearing mice. The surprising and remarkable outcomes for Se&#95;BSAL-HP prodrug NPs were probably due to the ROS triggering effect of boronate ester and selenium given together.

The present study was aimed to synthesize, characterize, and evaluate the angiopep-2 grafted PAMAM dendrimers (Den, G 3.0 NH 2 ) with and without PEGylation for the targeted and better delivery approach of temozolomide (TMZ) for the management of glioblastoma multiforme (GBM). Den-ANG and Den-PEG 2 -ANG conjugates were synthesized and characterized by 1 H NMR spectroscopy. The PEGylated (TMZ@Den-PEG 2 -ANG) and non-PEGylated (TMZ@Den-ANG) drug loaded formulations were prepared and characterized for particle size, zeta potential, entrapment efficiency, and drug loading. An in vitro release study at physiological (pH 7.4) and acidic pH (pH 5.0) was performed. Preliminary toxicity studies were performed through hemolytic assay in human RBCs. MTT assay, cell uptake, and cell cycle analysis were performed to evaluate the in vitro efficacy against GBM cell lines (U87MG). Finally, the formulations were evaluated in vivo in a Sprague-Dawley rat model for pharmacokinetics and organ distribution analysis. The 1 H NMR spectra confirmed the conjugation of angiopep-2 to both PAMAM and PEGylated PAMAM dendrimers, as the characteristic chemical shifts were observed in the range of 2.1 to 3.9 ppm. AFM results revealed that the surface of Den-ANG and Den-PEG 2 -ANG conjugates were rough. The particle size and zeta potential of TMZ@Den-ANG were observed to be 229.0 ± 17.8 nm and 9.06 ± 0.4 mV, respectively, whereas the same for TMZ@Den-PEG 2 -ANG were found to be 249.6 ± 12.9 nm and 10.9 ± 0.6 mV, respectively. The entrapment efficiency of TMZ@Den-ANG and TMZ@Den-PEG 2 -ANG were calculated to be 63.27 ± 5.1% and 71.48 ± 4.3%, respectively. Moreover, TMZ@Den-PEG 2 -ANG showed a better drug release profile with a controlled and sustained pattern at PBS pH 5.0 than at pH 7.4. The ex vivo hemolytic study revealed that TMZ@Den-PEG 2 -ANG was biocompatible in nature as it showed 2.78 ± 0.1% hemolysis compared to 4.12 ± 0.2% hemolysis displayed by TMZ@Den-ANG. The outcomes of the MTT assay inferred that TMZ@Den-PEG 2 -ANG possessed maximum cytotoxic effects against U87MG cells with IC 50 values of 106.62 ± 11.43 μM (24 h) and 85.90 ± 9.12 μM (48 h). In the case of TMZ@Den-PEG 2 -ANG, the IC 50 values were reduced by 2.23-fold (24 h) and 1.36-fold (48 h) in comparison to pure TMZ. The cytotoxicity findings were further confirmed by significantly higher cellular uptake of TMZ@Den-PEG 2 -ANG. Cell cycle analysis of the formulations suggested that the PEGylated formulation halts the cell cycle at G2/M phase with S-phase inhibition. In the in vivo studies, the half-life ( t 1/2 ) values of TMZ@Den-ANG and TMZ@Den-PEG 2 -ANG were enhanced by 2.22 and 2.76 times, respectively, than the pure TMZ. After 4 h of administration, the brain uptake values of TMZ@Den-ANG and TMZ@Den-PEG 2 -ANG were found to be 2.55 and 3.35 times, respectively, higher than that of pure TMZ. The outcomes of various in vitro and ex vivo experiments promoted the use of PEGylated nanocarriers for the management of GBM. Angiopep-2 grafted PEGylated PAMAM dendrimers can be potential and promising drug carriers for the targeted delivery of antiglioma drugs directly to the brain.

Breast cancer leads to the highest mortality among women resulting in a major clinical burden. Multidrug therapy is more efficient in such patients compared to monodrug therapy. Simultaneous combinatorial or co-delivery garnered significant interest in the past years. Caffeic acid (CFA) (a natural polyphenol) has received growing attention because of its anticarcinogenic and antioxidant potential. Bortezomib (BTZ) is a proteasome inhibitor and may be explored for treating breast cancer. Despite its high anticancer activity, the low water solubility and chemical instability restrict its efficacy against solid tumors. In the present study, we designed and investigated a HP-PCL ( N -2-hydroxypropylmethacrylamide-polycaprolactone) polymeric micellar (PMCs) system for the simultaneous delivery of BTZ and CFA in the treatment of breast cancer. The designed BTZ+CFA-HP-PCL PMCs were fabricated, optimized, and characterized for size, zeta potential, surface morphology, and in vitro drug release. Developed nanosized (174.6 ± 0.24 nm) PMCs showed enhanced cellular internalization and cell cytotoxicity in both MCF-7 and MDA-MB-231 cells. ROS (reactive oxygen species) levels were highest in BTZ-HP-PCL PMCs, while CFA-HP-PCL PMCs significantly ( p < 0.001) scavenged the ROS generated in 2',7'-dichlorofluorescein diacetate (DCFH-DA) assay. The mitochondrial membrane potential (MMP) assay revealed intense and significant green fluorescence in both types of cancer cells when treated with BTZ-HP-PCL PMCs ( p < 0.001) indicating apoptosis or cell death. The pharmacokinetic studies revealed that BTZ-HP-PCL PMCs and BTZ+CFA-HP-PCL PMCs exhibited the highest bioavailability, enhanced plasma half-life, decreased volume of distribution, and lower clearance rate than the pure combination of drugs. In the organ biodistribution studies, the combination of BTZ+CFA showed higher distribution in the spleen and the heart. Overall findings of in vitro studies surprisingly resulted in better therapeutic efficiency of BTZ-HP-PCL PMCs than BTZ+CFA-HP-PCL PMCs. However, the in vivo tumor growth inhibition study performed in tumor-induced mice concluded that the tumor growth was inhibited by both BTZ-HP-PCL PMCs and BTZ+CFA-HP-PCL PMCs ( p < 0.0001) more efficiently than pure BTZ and the combination (BTZ+CFA), which may be due to the conversion of boronate ester into boronic acid. Henceforth, the combination of BTZ and CFA provides further indications to be explored in the future to support the hypothesis that BTZ may work with polyphenol (CFA) in the acidic environment of the tumor.

Multi-drug resistance has shown to be one of the leading threats faced currently in many chemotherapeutic agents. Permeability glycoprotein (P-gp) is an efflux transporter in membrane, an integral part of ATP-binding cassette (ABC) transporters widely distributed in the body for cellular uptake. It is present enormously in cancerous cells and is in charge of generating transporter mediated resistance to treatments of tumorous cells in addition to blocking the entry of chemotherapeutic drugs into the cell. Natural P-gp inhibitors are derived from natural plant sources possessing basic structures like alkaloids, flavonoids, phenolics, terpenoids, saponins, sapogenins, sterols, coumarins and miscellaneous structures acting on P-gp substrate for inhibition of multi-drug resistance via inhibiting the efflux pump. They do not depict their action on the healthy cells and thus it is proven to be more effective and less toxic than synthetic P-gp inhibitor leading to enhancement in bioavailability of chemotherapeutic drugs. The significant objective of the present review is surfing through the impact of natural P-gp inhibitors having basic structures derived from the plant sources and how it inhibits the resistance of chemotherapeutic drugs together with how well it delivers chemotherapy medicines., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Autoimmune disease is increasing widely, and the biologicals in autoimmune disease play a vital role in the cure. Biologicals have an affinity to bind the specific target molecule and suppress inflammation. The different biologicals are used to treat various autoimmune diseases by preventing the cytokines from unlocking cells and causing inflammation. Each biologic targets a different cytokine. The common classes of biologic that are used to treat autoimmune disease are i) Tumor Necrosis Factor-alpha (TNFα) inhibitors and ii) Interleukin Inhibitors (IL). Along with biologics, nanomedicine has shown to be a successful method for creating customized nanomaterials with the potential to deliver medicinal agents to particular organs or tissues drugs without causing immunosuppressive or immunostimulatory adverse effects. This article reviews biologics used in treating Autoimmune Disease (AD) and the mechanism involved. The examination of current developments that have been made to create innovative nanoparticle-based therapies for autoimmune illnesses and their inclusion in vaccines. Also, recent clinical trials display nanosystem strategies for treating AD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Cytochrome (CYP) enzymes catalyze the metabolism of numerous exogenous and endogenous substrates in cancer therapy leading to significant drug interactions due to their metabolizing effect. CYP enzymes play an important role in the metabolism of essential anticancer medications. They are shown to be overexpressed in tumor cells at numerous locations in the body. This overexpression could be a result of lifestyle factors, presence of hereditary variants of CYP (Bio individuality) and multi-drug resistance. This finding has sparked an interest in using CYP inhibitors to lower their metabolizing activity as a result facilitating anti-cancer medications to have a therapeutic impact. As a result of the cytotoxic nature of synthetic enzyme inhibitors and the increased prevalence of herbal medication, natural CYP inhibitors have been identified as an excellent way to inhibit overexpression sighting their tendency to show less cytotoxicity, lesser adverse drug reactions and enhanced bioavailability. Nonetheless, their effect of lowering the hindrance caused in chemotherapy due to CYP enzymes remains unexploited to its fullest. It has been observed that there is a substantial decrease in first pass metabolism and increase in intestinal absorption of chemotherapeutic drugs like paclitaxel when administered along with flavonoids which help suppress certain specific cytochrome enzymes which play a role in paclitaxel metabolism. This review elaborates on the role and scope of phytochemicals in primary, secondary and tertiary care and how targeted prevention of cancer could be a breakthrough in the field of chemotherapy and oncology. This opens up a whole new area of research for delivery of these natural inhibitors along with anticancer drugs with the help of liposomes, micelles, nanoparticles, the usage of liquid biopsy analysis, artificial intelligence in medicine, risk assessment tools, multi-omics and multi-parametric analysis. Further, the site of action, mechanisms, metabolites involved, experimental models, doses and observations of two natural compounds, quercetin & thymoquinone, and two plant extracts, liquorice & garlic on CYP enzymes have been summarized., (© 2022. The Author(s).)

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&#95;GEM NPs) of 232 ± 9.69 nm with narrow distribution (PDI < 0.5) and zeta potential of - 19 ± 0.97 mV was fabricated. GEM was successfully loaded in the SA-CS NPs, depicting prolonged and biphasic drug release pattern more elated at low pH. Pronounced cellular uptake (FITC tagged) and cytotoxicity (IC 50 487.4 nM) was observed in SA-CS&#95;GEM NPs against A549 cells. IC 50 for SA-CS&#95;GEM NPs plunged with an increase in the time points from 24 to 72 h. Concentration-dependent haemolytic study confirmed significant haemocompatibility of SA-CS&#95;GEM NPs. Pharmacokinetic study was performed on Sprague-Dawley rats and the kinetic parameters were calculated using PKSolver 2.0. Results demonstrated a consequential refinement of 2.98 times in modified SA-CS&#95;GEM NPs with a significant increase in retention time, bioavailability and elimination half-life, and decrease in elimination rate constant and volume of distribution in comparison to CS&#95;GEM NPs. Therefore, SA-CS shell core nanoparticles could be a beneficial approach to target and treat NSCLC (non-small cell lung cancer) and direct for research possibilities to target the other tumour cells., (© 2021. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

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., Competing Interests: The authors declare no competing financial interest., (© 2021 The Author(s).)

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-delivery of a natural phytoconstituent, crocin (carotenoid), and a commonly prescribed drug, doxorubicin, was attempted using a nanoparticulate platform in the form of PLGA nanoparticles. Doxorubicin was chemically conjugated, while crocin was encapsulated physically in prepared PLGA nanoparticles (PDCR NPs). Prepared NPs were well-characterized for size, ζ, and surface morphology. PDCR NPs were of 174.2 ± 1.57 nm in size. The transmission electron microscopy (TEM) and atomic force microscopy (AFM) images revealed the spherical shape and smooth surface morphology of the nanoparticles, respectively. The entrapment efficiency and drug loading were found to be 58.95 ± 2.58 and 13.89 ± 1.09%, respectively. The drug release pattern of PDCR NPs showed a sustained and controlled release pattern throughout 48 h in PBS buffer pH 7.4 and acetate buffer pH 6.5. PDCR NPs were significantly less hemolytic than doxorubicin ( p < 0.0001). Investigational formulation selectively produced cytotoxic effects on breast cancer cells via decreasing reactive oxygen species (ROS) and altering the mitochondrial potential that led to apoptosis with cell-cycle arrest at the G2/M phase. Prepared NPs were able to upregulate the caspase levels as well as efficient uptake by cells in a time-dependent manner. In vivo plasma drug profile studies in healthy rats revealed prolonged persistence of crocin and doxorubicin in systemic circulation. Additionally, the PDCR NPs portrayed reduced tumor volume as compared to control groups in the tumor-induced animal studies, which were favorable. Conclusively, the co-delivery of natural anticancer bioactive crocin along with doxorubicin in PDCR NPs provides a possible controlled-release nanoplatform for efficient drug delivery in vitro and in vivo .

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 naïve 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 the IC 50 value against the blood stage of asexual P. falciparum 3D7 strains was significantly (p < 0.01) less (2.862 ± 0.103 μM) for Gel-LA-PQ-NPs than naïve PQ (3.879 ± 0.655 μM). In vivo pharmacokinetic parameters of Gel-LA-PQ-NPs such as half-life and AUC were significantly higher for Gel-LA-PQ-NPs, i.e., with higher bioavailability. Galactosylation of the NPs led to liver targeting of the PQ in animal studies. Approximately eight-fold higher accumulation of PQ was observed in liver compared to pure drug (i.e., PQ). Conclusively, the prepared galactosylated gelatin nanocarrier holds the promising potential and hepatic targetability of an antimalarial, maintaining its safety and biocompatibility.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Application of pharmaceutical nanotechnology (nanomedicines) for plant actives and extracts, is gaining a tremendous growth and interest among the scientists. This emerging herbal revolution has headed towards the development of another approaches for the delivery of poorly soluble herbal bioactives and plant extracts for enhancing their bioavailability and efficacy. In the same context, a majority of pharmaceutical nanotechnologies and targeting strategies including phytosomes, nanoparticles, hydrogels, microspheres, transferosomes and ethosomes, self nano emulsifying drug delivery systems (SNEDDS), self micro emulsifying drug delivery systems (SMEDDS) has been applied for the delivery of bioactives and plant extracts and were identified and explored. These pharmaceutical nanotechnologies have been proven to be the most efficient and reliable delivery systems, as these enhance the solubility, absorption, pharmacokinetics, bioavailability and provide protection from toxicity. Considering these aspects, the present review highlights the present scenario related to the expansion of novel herbal formulations utilizing the nanotechnologies and compilation of their delivery types and mechanism, methodology, loaded drug, drug size, entrapment efficiency of drug, in vivo activity and its application. Moreover, this review article provides an understanding of therapeutic efficacy of the herbal medicines to be loaded into the novel drug delivery system for various biomedical applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cancer is the major cause of fatality and the number of new cases is increasing incessantly. Conventional therapies and existing anticancer agents cause serious side effects and expand the patient's lifespan by a few years. There is the need to exploit alternative anticancer agents and novel drug delivery system to deliver these agents to the tumor site for the prevention of cancer. Recently, biologically active compounds isolated from plants used for the management of cancer have been the heart of interest. Capsaicin is a major pungent agent present in the chili peppers that is heavily consumed in the world. Capsaicin has demonstrated effectiveness as an anticancer agent, but a restraining factor is its pungency, extremely low aqueous solubility, and poor oral bioavailability which impede its use as an anticancer agent. Many technologies have been developed and applied to conquer this drawback. We bring to light the benefits of this phytoconstituent for treating different types of cancer. We also discussed some of the delivery approaches that have already made an impact by either delivering a drug to target tissue or increasing its bioavailability by many folds.

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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., (© 2014 Royal Pharmaceutical Society.)

Stimuli triggered polymers provide a variety of applications related with the biomedical fields. Among various stimuli triggered mechanisms, thermoresponsive mechanisms have been extensively investigated, as they are relatively more convenient and effective stimuli for biomedical applications. In a contemporary approach for achieving the sustained action of proteins, peptides and bioactives, injectable depots and implants have always remained the thrust areas of research. In the same series, Poloxamer based thermogelling copolymers have their own limitations regarding biodegradability. Thus, there is a need to have an alternative biomaterial for the formulation of injectable hydrogel, which must remain biocompatible along with safety and efficacy. In the same context, poly(ethylene glycol) (PEG) based copolymers play a crucial role as a biomedical material for biomedical applications, because of their biocompatibility, biodegradability, thermosensitivity and easy controlled characters. This review stresses on the physicochemical property, stability and composition prospects of smart PEG/poly(lactic-co-glycolic acid) (PLGA) based thermoresponsive injectable hydrogels, recently utilized for biomedical applications. The manuscript also highlights the synthesis scheme and stability characteristics of these copolymers, which will surely help the researchers working in the same area. We have also emphasized the applied use of these smart copolymers along with their formulation problems, which could help in understanding the possible modifications related with these, to overcome their inherent associated limitations., (© 2013.)

Emulgel is an emerging topical drug delivery system to which if more effort is paid towards its formulation & development with more number of topically effective drugs it will prove a boon for derma care & cosmetology. Emulgels are either emulsion of oil in water or water in oil type, which is gelled by mixing it with gelling agent. Incorporation of emulsion into gel increases its stability & makes it a dual control release system. Due to lack of excess oily bases & insoluble excipients, it shows better drug release as compared to other topical drug delivery system. Presence of gel phase makes it a non greasy & favors good patient compliance. These reviews give knowledge about Emulgel including its properties, advantages, formulation considerations, and its recent advances in research field. All factors such as selection of gelling agent, oil agent, emulsifiers influencing the stability and efficacy of Emulgel are discussed. All justifications are described in accordance with the research work carried out by various scientists. These brief reviews on formulation method have been included. Current research works that carried out on Emulgel are also discussed and highlighted the wide utility of Emulgel in topical drug delivery system. After the vast study, it can be concluded that the Emulgels appear better & effective drug delivery system as compared to other topical drug delivery system. The comprehensive analysis of rheological and release properties will provide an insight into the potential usage of Emulgel formulation as drug delivery system., (© 2013.)

This study presents development and evaluation of novel sustained release system of diclofenac sodium (DS) prepared by solid dispersion (SD) technique using Eudragit E 100 (EE 100) and/or Eudragit S 100 (ES 100) as carriers. Compatibility of the drug and its crystalline nature in the SD were examined using Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD) and differential scanning calorimetry (DSC). The drug was relatively stable, amorphous in the SD. The greater amount of EE100 or ES 100 in the SD slowed down the release rates with smaller dissolution efficiency and hence the mean dissolution time was enhanced. Moreover, combined carriers of EE 100-ES 100 exhibited more dissolution retarding effect than any of the carriers. The release of drug followed anomalous transport in artificial intestinal juice (pH 6.8).

A novel diclofenac sodium (DS) loaded interpenetrating polymer network (IPN) beads of pectin and hydrolyzed polyacrylamide-graft-sodium alginate (PAAm-g-SA) was developed through ionotropic gelation and covalent cross-linking. The graft copolymer was synthesized by free radical polymerization under the nitrogen atmosphere followed by alkaline hydrolysis. The grafting, alkaline hydrolysis, and characterization of beads were confirmed by Fourier transforms infrared spectroscopy. The crystalline structure of drug after encapsulation into IPN beads were evaluated by differential scanning colorimetry and X-ray diffraction analyses. DS encapsulation was up to 96.45 %. The effect of hydrolyzed graft copolymer/pectin ratios and glutaraldehyde concentration on drug release in acidic and phosphate buffer solutions were investigated. The release of drug was significantly increased with increase of pH. The release of drug depends on the extent of cross-linking. The results indicated that IPN beads of hydrolyzed PAAm-g-SA and pectin could be used for sustained release of DS.

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.

Introduction: Current research efforts focused on the design and evaluation of drug delivery systems that are easy to administer require decreased administration frequency, and provide sustained drug release in order to increase clinical efficacy and compliance of the patients. The gel forming smart polymeric formulations offer numerous applications resemble sustained and prolonged action in contrast to conventional drug delivery systems., Areas Covered: Article summarizes type of bioactive, sol-gel triggering factors, dose, rationales, and polymers involved in gelation with respect to their route of administration. A lot of work has been done with smart polymeric gelling system taking the advantage of stimuli (temperature and pH) triggered sol-gel phase-transition in the administered area that have great prospective in biomedical and pharmaceutical applications, particularly in target-specific controlled drug delivery systems., Expert Opinion: Although the principle of gelation is so attractive, key issues remain to be solved which include (i) variability of the drug release, (ii) avoidance of burst release in case of depot formulation, and (iii) issues related to toxicity. Unfortunately, till now area concerning the detailed processes of the gelling formation is still not much explored. Despite this proclamation, many efforts are made in industry and institutions to improve concerned approaches. New materials and approaches enter the preclinical and clinical phases and one can be sure that this strategy will gain further clinical importance within the next years. Thus, this review article will assuredly serve as an informative tool for the innovators working in the concern area.

Alginate is a non-toxic, biocompatible and biodegradable natural polymer with a number of peculiar physicochemical properties for which it has wide applications in drug delivery and cell delivery systems. Hydrogel formation can be obtained by interactions of anionic alginates with multivalent inorganic cations by simple ionotropic gelation method. Hydrophilic polymeric network of three dimensional cross linked structures of hydrogels absorb substantial amount of water or biological fluids. Among the numerous biomaterials used for hydrogel formation alginate has been and will continue to be one of the most important biomaterial. Therefore, in view of the vast literature support, we focus in this review on alginate - based hydrogel as drug delivery and cell delivery carriers for biomedical applications. Various properties of alginates, their hydrogels and also various techniques used for preparing alginate hydrogels have been reviewed.

Traditional medicines that formed the basis of health care throughout the world since the earliest days of mankind are still widely used and have considerable importance in international trade. Recognition of their clinical, pharmaceutical, and economic value is still growing, although this varies widely between countries and therefore regulation of exploitation and exportation is essential, together with international cooperation and coordination for their conservation so as to ensure their availability for the future. World Health Organization and European Union issued the guidelines defined the basic criteria for the evaluation of quality, safety, and efficacy of herbal medicines with the goal of assisting national regulatory authorities, scientific organizations, and manufacturers in assessing documentation, submissions, and dossiers in respect of such products. Legislative controls in respect of medicinal plants have not evolved around a structured control model. There are different ways in which countries define medicinal plants or herbs or products derived from them. The present review highlights the status of different countries adopted various approaches to licensing, dispensing, manufacturing, and trading to ensure their safety, quality, and efficacy.