Displaying publications 1 - 20 of 81 in total

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  1. Gorain B, Rajeswary DC, Pandey M, Kesharwani P, Kumbhar SA, Choudhury H
    Curr Pharm Des, 2020;26(19):2233-2246.
    PMID: 32167424 DOI: 10.2174/1381612826666200313125613
    Increasing incidence of demented patients around the globe with limited FDA approved conventional therapies requires pronounced research attention for the management of the demented conditions in the growing elderly population in the developing world. Dementia of Alzheimer's type is a neurodegenerative disorder, where conventional therapies are available for symptomatic treatment of the disease but possess several peripheral toxicities due to lack of brain targeting. Nanotechnology based formulations via intranasal (IN) routes of administration have shown to improve therapeutic efficacy of several therapeutics via circumventing blood-brain barrier and limited peripheral exposure. Instead of numerous research on polymeric and lipid-based nanocarriers in the improvement of therapeutic chemicals and peptides in preclinical research, a step towards clinical studies still requires wide-ranging data on safety and efficacy. This review has focused on current approaches of nanocarrierbased therapies on Alzheimer's disease (AD) via the IN route for polymeric and lipid-based nanocarriers for the improvement of therapeutic efficacy and safety. Moreover, the clinical application of IN nanocarrier-based delivery of therapeutics to the brain needs a long run; however, proper attention towards AD therapy via this platform could bring a new era for the AD patients.
  2. Gorain B, Al-Dhubiab BE, Nair A, Kesharwani P, Pandey M, Choudhury H
    Curr Pharm Des, 2021;27(43):4404-4415.
    PMID: 34459377 DOI: 10.2174/1381612827666210830095941
    The advancement of delivery tools for therapeutic agents has brought several novel formulations with increased drug loading, sustained release, targeted delivery, and prolonged efficacy. Amongst the several novel delivery approaches, multivesicular liposome has gained potential interest because this delivery system possesses the above advantages. In addition, this multivesicular liposomal delivery prevents degradation of the entrapped drug within the physiological environment while administered. The special structure of the vesicles allowed successful entrapment of hydrophobic and hydrophilic therapeutic agents, including proteins and peptides. Furthermore, this novel formulation could maintain the desired drug concentration in the plasma for a prolonged period, which helps to reduce the dosing frequencies, improve bioavailability, and safety. This tool could also provide stability of the formulation, and finally gaining patient compliance. Several multivesicular liposomes received approval for clinical research, while others are at different stages of laboratory research. In this review, we have focused on the preparation of multivesicular liposomes along with their application in different ailments for the improvement of the performance of the entrapped drug. Moreover, the challenges of delivering multivesicular vesicles have also been emphasized. Overall, it could be inferred that multivesicular liposomal delivery is a platform of advanced drug delivery with improved efficacy and safety.
  3. Kumar Bandaru R, Rout SR, Kenguva G, Gorain B, Alhakamy NA, Kesharwani P, et al.
    Front Pharmacol, 2021;12:780582.
    PMID: 34858194 DOI: 10.3389/fphar.2021.780582
    The pharmacokinetics profile of active pharmaceutical ingredients (APIs) in the solid pharmaceutical dosage forms is largely dependent on the solid-state characteristics of the chemicals to understand the physicochemical properties by particle size, size distribution, surface area, solubility, stability, porosity, thermal properties, etc. The formation of salts, solvates, and polymorphs are the conventional strategies for altering the solid characteristics of pharmaceutical compounds, but they have their own limitations. Cocrystallization approach was established as an alternative method for tuning the solubility, permeability, and processability of APIs by introducing another compatible molecule/s into the crystal structure without affecting its therapeutic efficacy to successfully develop the formulation with the desired pharmacokinetic profile. In the present review, we have grossly focused on cocrystallization, particularly at different stages of development, from design to production. Furthermore, we have also discussed regulatory guidelines for pharmaceutical industries and challenges associated with the design, development and production of pharmaceutical cocrystals with commercially available cocrystal-based products.
  4. Hejmady S, Pradhan R, Alexander A, Agrawal M, Singhvi G, Gorain B, et al.
    Drug Discov Today, 2020 12;25(12):2227-2244.
    PMID: 33011342 DOI: 10.1016/j.drudis.2020.09.031
    A tumor serves as a major avenue in drug development owing to its complexity. Conventional therapies against tumors possess limitations such as suboptimal therapeutic efficacy and extreme side effects. These display poor pharmacokinetics and lack specific targeting, with non-specific distribution resulting in systemic toxicity. Therefore, nanocarriers targeted against cancers are increasingly being explored. Nanomedicine aids in maintaining a balance between efficacy and toxicity by specifically accumulating in tumors. Nanotherapeutics possess advantages such as increased solubility of chemotherapeutics, encapsulation of multiple drugs and improved biodistribution, and can ensure tumor-directed drug delivery and release via the approaches of passive targeting and active targeting. This review aims to offer a general overview of the current advances in tumor-targeting nanocarriers for clinical and diagnostic use.
  5. Choudhury H, Pandey M, Lim YQ, Low CY, Lee CT, Marilyn TCL, et al.
    Mater Sci Eng C Mater Biol Appl, 2020 Jul;112:110925.
    PMID: 32409075 DOI: 10.1016/j.msec.2020.110925
    Wounds associated with diabetes mellitus are the most severe co-morbidities, which could be progressed to cause cell necrosis leading to amputation. Statistics on the recent status of the diabetic wounds revealed that the disease affects 15% of diabetic patients, where 20% of them undergo amputation of their limb. Conventional therapies are found to be ineffective due to changes in the molecular architecture of the injured area, urging novel deliveries for effective treatment. Therefore, recent researches are on the development of new and effective wound care materials. Literature is evident in providing potential tools in topical drug delivery for wound healing under the umbrella of nanotechnology, where nano-scaffolds and nanofibers have shown promising results. The nano-sized particles are also known to promote healing of wounds by facilitating proper movement through the healing phases. To date, focuses have been made on the efficacy of silver nanoparticles (AgNPs) in treating the diabetic wound, where these nanoparticles are known to exploit potential biological properties in producing anti-inflammatory and antibacterial activities. AgNPs are also known to activate cellular mechanisms towards the healing of chronic wounds; however, associated toxicities of AgNPs are of great concern. This review is an attempt to illustrate the use of AgNPs in wound healing to facilitate this delivery system in bringing into clinical applications for a superior dressing and treatment over wounds and ulcers in diabetes patients.
  6. Choudhury H, Pandey M, Yin TH, Kaur T, Jia GW, Tan SQL, et al.
    Mater Sci Eng C Mater Biol Appl, 2019 Aug;101:596-613.
    PMID: 31029353 DOI: 10.1016/j.msec.2019.04.005
    Multidrug resistance (MDR) is one of the key barriers in chemotherapy, leading to the generation of insensitive cancer cells towards administered therapy. Genetic and epigenetic alterations of the cells are the consequences of MDR, resulted in drug resistivity, which reflects in impaired delivery of cytotoxic agents to the cancer site. Nanotechnology-based nanocarriers have shown immense shreds of evidence in overcoming these problems, where these promising tools handle desired dosage load of hydrophobic chemotherapeutics to facilitate designing of safe, controlled and effective delivery to specifically at tumor microenvironment. Therefore, encapsulating drugs within the nano-architecture have shown to enhance solubility, bioavailability, drug targeting, where co-administered P-gp inhibitors have additionally combat against developed MDR. Moreover, recent advancement in the stimuli-sensitive delivery of nanocarriers facilitates a tumor-targeted release of the chemotherapeutics to reduce the associated toxicities of chemotherapeutic agents in normal cells. The present article is focused on MDR development strategies in the cancer cell and different nanocarrier-based approaches in circumventing this hurdle to establish an effective therapy against deadliest cancer disease.
  7. Pandey M, Choudhury H, Yeun OC, Yin HM, Lynn TW, Tine CLY, et al.
    Curr Pharm Biotechnol, 2018;19(4):276-292.
    PMID: 29874994 DOI: 10.2174/1389201019666180605125234
    BACKGROUND: Targeting chemotherapeutic agents to the tumor tissues and achieving accumulation with ideal release behavior for desired therapy requires an ideal treatment strategy to inhibit division of rapid growing cancerous cells and as an outcome improve patient's quality of life. However, majority of the available anticancer therapies are well known for their systemic toxicities and multidrug resistance.

    METHODS: Application of nanotechnology in medicine have perceived a great evolution during past few decades. Nanoemulsion, submicron sized thermodynamically stable distribution of two immiscible liquids, has gained extensive importance as a nanocarrier to improve chemotherapies seeking to overcome the limitations of drug solubilization, improving systemic delivery of the chemotherapeutics to the site of action to achieve a promising inhibitory in tumor growth profile with reduced systemic toxicity.

    RESULTS AND CONCLUSION: This review has focused on potential application of nanoemulsion in the translational research and its role in chemotherapy using oral, parenteral and transdermal route to enhance systemic availability of poorly soluble drug. In summary, nanoemulsion is a multifunctional nanocarrier capable of enhancing drug delivery potential of cytotoxic agents, thereby, can improve the outcomes of cancer treatment by increasing the life-span of the patient and quality of life, however, further clinical research and characterization of interactive reactions should need to be explored.

  8. Choudhury H, Pandey M, Chin PX, Phang YL, Cheah JY, Ooi SC, et al.
    Drug Deliv Transl Res, 2018 10;8(5):1545-1563.
    PMID: 29916012 DOI: 10.1007/s13346-018-0552-2
    Treatment of glioblastoma multiforme (GBM) is a predominant challenge in chemotherapy due to the existence of blood-brain barrier (BBB) which restricts delivery of chemotherapeutic agents to the brain together with the problem of drug penetration through hard parenchyma of the GBM. With the structural and mechanistic elucidation of the BBB under both physiological and pathological conditions, it is now viable to target central nervous system (CNS) disorders utilizing the presence of transferrin (Tf) receptors (TfRs). However, overexpression of these TfRs on the GBM cell surface can also help to avoid restrictions of GBM cells to deliver chemotherapeutic agents within the tumor. Therefore, targeting of TfR-mediated delivery could counteract drug delivery issues in GBM and create a delivery system that could cross the BBB effectively to utilize ligand-conjugated drug complexes through receptor-mediated transcytosis. Hence, approach towards successful delivery of antitumor agents to the gliomas has been making possible through targeting these overexpressed TfRs within the CNS and glioma cells. This review article presents a thorough analysis of current understanding on Tf-conjugated nanocarriers as efficient drug delivery system.
  9. Sharma AK, Gothwal A, Kesharwani P, Alsaab H, Iyer AK, Gupta U
    Drug Discov Today, 2017 02;22(2):314-326.
    PMID: 27671487 DOI: 10.1016/j.drudis.2016.09.013
    Dendrimers are novel nanoarchitectures with unique properties including a globular 3D shape, a monodispersed unimicellar nature and a nanometric size range. The availability of multiple peripheral functional groups and tunable surface engineering enable the facile modification of the dendrimer surface with different therapeutic drugs, diagnostic agents and targeting ligands. Drug encapsulation, and solubilizing and passive targeting also equally contribute to the therapeutic use of dendrimers. In this review, we highlight recent advances in the delivery of anticancer drugs using dendrimers, as well as other biomedical and diagnostic applications. Taken together, the immense potential and utility of dendrimers are envisaged to have a significant positive impact on the growing arena of drug delivery and targeting.
  10. Kumar H, Mishra G, Sharma AK, Gothwal A, Kesharwani P, Gupta U
    Pharm Nanotechnol, 2017;5(3):203-214.
    PMID: 28521670 DOI: 10.2174/2211738505666170515113936
    BACKGROUND: The convoluted pathophysiology of brain disorders along with penetration issue of drugs to brain represents major hurdle that requires some novel therapies. The blood-brain barrier (BBB) denotes a rigid barrier for delivery of therapeutics in vivo; to overcome this barrier, intranasal delivery is an excellent strategy to deliver the drug directly to brain via olfactory and trigeminal nerve pathways that originate as olfactory neuro-epithelium in the nasal cavity and terminate in brain.

    METHOD: Kind of therapeutics like low molecular weight drugs can be delivered to the CNS via this route. In this review, we have outlined the anatomy and physiological aspect of nasal mucosa, certain hurdles, various strategies including importance of muco-adhesive polymers to increase the drug delivery and possible clinical prospects that partly contribute in intranasal drug delivery.

    RESULTS: Exhaustive literature survey related to intranasal drug delivery system revealed the new strategy that circumvents the BBB, based on non-invasive concept for treating various CNS disorders. Numerous advantages like prompt effects, self-medication through wide-ranging devices, and the frequent as well protracted dosing are associated with this novel route.

    CONCLUSION: Recently few reports have proven that nasal to brain drug delivery system bypasses the BBB. This novel route is associated with targeting efficiency and less exposure of therapeutic substances to non-target site. Nevertheless, this route desires much more research into the safe transferring of therapeutics to the brain. Role of muco-adhesive polymer and surface modification with specific ligands are area of interest of researcher to explore more about this.

  11. Khan I, Kumar H, Mishra G, Gothwal A, Kesharwani P, Gupta U
    Curr Pharm Des, 2017;23(35):5315-5326.
    PMID: 28875848 DOI: 10.2174/1381612823666170829164828
    BACKGROUND: Delivery of chemotherapeutic drugs for the diagnosis and treatment of cancer is becoming advanced day by day. However, the challenge of the effective delivery system still does exist. In various types of cancers, breast cancer is the most commonly diagnosed cancer among women. Breast cancer is a combination of different diseases. It cannot be considered as only one entity because there are many specific patient factors, which are involved in the development of this disease. Nanotechnology has opened a new area in the effective treatment of breast cancer due to the several benefits offered by this technology.

    METHODS: Polymeric nanocarriers are among one of the effective delivery systems, which has given promising results in the treatment of breast cancers. Nanocarriers does exert their anticancer effect either through active or passive targeting mode.

    RESULTS: The use of nanocarriers has been resolute about the adverse effects of chemotherapeutic drugs such as poor solubility and less penetrability in tumor cells.

    CONCLUSION: The present review is focused on recent developments regarding polymeric nanocarriers, such as polymeric micelles, polymeric nanoparticles, dendrimers, liposomes, nanoshells, fullerenes, carbon nanotubes (CNT) and quantum dots, etc. for their recent advancements in breast cancer therapy.

  12. Kesharwani P, Gothwal A, Iyer AK, Jain K, Chourasia MK, Gupta U
    Drug Discov Today, 2017 Jul 08.
    PMID: 28697371 DOI: 10.1016/j.drudis.2017.06.009
    Highly controllable dendritic structural design means dendrimers are a leading carrier in drug delivery applications. Dendrimer- and other nanocarrier-based hybrid systems are an emerging platform in the field of drug delivery. This review is a compilation of increasing reports of dendrimer interactions, such as dendrimer-liposome, dendrimer-carbon-nanotube, among others, known as hybrid carriers. This should prompt entirely new research with promising results for these hybrid carriers. It is assumed that such emerging hybrid nanosystems - from combining two already-established drug delivery platforms - could lead the way for the development of newer delivery systems with multiple applicability for latent theranostic applications in the future.
  13. Hussain Z, Thu HE, Shuid AN, Kesharwani P, Khan S, Hussain F
    Biomed Pharmacother, 2017 Sep;93:596-608.
    PMID: 28686974 DOI: 10.1016/j.biopha.2017.06.087
    For many decades, natural herbal medicines, polyherbal formulations and/or decoctions of plant-derived materials have widely been accepted as alternative complementary therapies for the treatment, cure or prevention of a wide range of acute and chronic skin diseases including chronic herpes, prurigo, acute and chronic wounds, psoriasis and atopic dermatitis (AD). This review was aimed to summarize and critically discuss about the therapeutic viability and clinical applicability of natural herbal medicines for the treatment of AD in human. The critical analysis of the literature revealed that oral (in the form of capsules, syrup or granules) and/or topical application (alone or in conjunction with wet-wrap dressing and/or acupuncture) of natural herbal medicines exhibit remarkable potential for the treatment of mild-to-severe AD in adults, children, infants and in the pregnant women. In this review, the clinical efficacy of various herbal formulations such as Chinese herbal therapies, Korean medicines, Iranian medicines, honey, natural herbal oils (coconut oil, olive oil and mineral oil), beeswax, dodder seeds and whey for the treatment of AD has been discussed. The clinical anti-AD efficacy of these complementary therapies has been observed in terms of down-regulation in Scoring Atopic Dermatitis (SCORAD) index, erythematic intensity, Children's Dermatology Life Quality Index (CDLQI), Dermatology Life Quality Index (DLQI), pruritus and itching frequency, transepidermal water loss (TEWL) and expression of AD-mediated chemokines. Conclusively, we recognized that natural herbal medicines demonstrate remarkable clinical efficacy when used alone or in conjunction with other complementary therapies for the treatment of AD in patients of all ages as well as pregnant women.
  14. Gorain B, Choudhury H, Pandey M, Kesharwani P, Abeer MM, Tekade RK, et al.
    Biomed Pharmacother, 2018 Aug;104:496-508.
    PMID: 29800914 DOI: 10.1016/j.biopha.2018.05.066
    Myocardial infarction (cardiac tissue death) is among the most prevalent causes of death among the cardiac patients due to the inability of self-repair in cardiac tissues. Myocardial tissue engineering is regarded as one of the most realistic strategies for repairing damaged cardiac tissue. However, hindrance in transduction of electric signals across the cardiomyocytes due to insulating properties of polymeric materials worsens the clinical viability of myocardial tissue engineering. Aligned and conductive scaffolds based on Carbon nanotubes (CNT) have gained remarkable recognition due to their exceptional attributes which provide synthetic but viable microenvironment for regeneration of engineered cardiomyocytes. This review presents an overview and critical analysis of pharmaceutical implications and therapeutic feasibility of CNT based scaffolds in improving the cardiac tissue regeneration and functionality. The expository analysis of the available evidence revealed that inclusion of single- or multi-walled CNT into fibrous, polymeric, and elastomeric scaffolds results in significant improvement in electrical stimulation and signal transduction through cardiomyocytes. Moreover, incorporation of CNT in engineering scaffolds showed a greater potential of augmenting cardiomyocyte proliferation, differentiation, and maturation and has improved synchronous beating of cardiomyocytes. Despite promising ability of CNT in promoting functionality of cardiomyocytes, their presence in scaffolds resulted in substantial improvement in mechanical properties and structural integrity. Conclusively, this review provides new insight into the remarkable potential of CNT aligned scaffolds in improving the functionality of engineered cardiac tissue and signifies their feasibility in cardiac tissue regenerative medicines and stem cell therapy.
  15. Pandey M, Choudhury H, Yi CX, Mun CW, Phing GK, Rou GX, et al.
    Curr Drug Targets, 2018;19(15):1782-1800.
    PMID: 29792143 DOI: 10.2174/1389450119666180523092100
    Diabetes mellitus, a metabolic disorder of glucose metabolism, is mainly associated with insulin resistance to the body cells, or impaired production of insulin by the pancreatic β-cells. Insulin is mainly required to regulate glucose metabolism in type 1 diabetes mellitus patients; however, many patients with type 2 diabetes mellitus also require insulin, especially when their condition cannot be controlled solely by oral hypoglycemic agents. Hence, major research is ongoing attempting to improve the delivery of insulin in order to make it more convenient to patients who experience side effects from the conventional treatment procedure or non-adherence to insulin regimen due to multiple comorbid conditions. Conventionally, insulin is administered via subcutaneous route which is also one of the sole reasons of patient's non-compliance due to the invasiveness of this method. Several attempts have been done to improve patient compliance, reduce side effects, improve delivery adherence, and to enhance the pharmaceutical performance of the insulin therapy. Despite facing substantial challenges in developing efficient delivery systems for insulin, vast research studies have been carried out for the development of smart delivery systems to deliver insulin via ocular, buccal, pulmonary, oral, transdermal, as well as rectal routes. Therefore, the present review was aimed to overview the challenges encountered with the current insulin delivery systems and to summarize recent advancements in technology of various novel insulin delivery systems being discovered and introduced in the current market.
  16. Amjad MW, Amin MC, Katas H, Butt AM, Kesharwani P, Iyer AK
    Mol Pharm, 2015 Dec 7;12(12):4247-58.
    PMID: 26567518 DOI: 10.1021/acs.molpharmaceut.5b00827
    Multidrug resistance poses a great challenge to cancer treatment. In order to improve the targeting and codelivery of small interfering RNA (siRNA) and doxorubicin, and to overcome multidrug resistance, we conjugated a cholic acid-polyethylenimine polymer with folic acid, forming CA-PEI-FA micelles. CA-PEI-FA exhibited a low critical micelle concentration (80 μM), small average particle size (150 nm), and positive zeta potential (+ 12 mV). They showed high entrapment efficiency for doxorubicin (61.2 ± 1.7%, w/w), forming D-CA-PEI-FA, and for siRNA, forming D-CA-PEI-FA-S. X-ray photoelectron spectroscopic analysis revealed the presence of external FA on D-CA-PEI-FA micelles. About 25% doxorubicin was released within 24 h at pH 7.4, while more than 30% release was observed at pH 5. The presence of FA enhanced micelle antitumor activity. The D-CA-PEI-FA and D-CA-PEI-FA-S micelles inhibited tumor growth in vivo. No significant differences between their in vitro cytotoxic activities or their in vivo antitumor effects were observed, indicating that the siRNA coloading did not significantly increase the antitumor activity. Histological analysis revealed that tumor tissues from mice treated with D-CA-PEI-FA or D-CA-PEI-FA-S showed the lowest cancer cell density and the highest levels of apoptosis and necrosis. Similarly, the livers of these mice exhibited the lowest level of dihydropyrimidine dehydrogenase among all treated groups. The lowest serum vascular endothelial growth factor level (VEGF) (24.4 pg/mL) was observed in mice treated with D-CA-PEI-FA-S micelles using siRNA targeting VEGF. These findings indicated that the developed CA-PEI-FA nanoconjugate has the potential to achieve targeted codelivery of drugs and siRNA.
  17. Luong D, Kesharwani P, Deshmukh R, Mohd Amin MCI, Gupta U, Greish K, et al.
    Acta Biomater, 2016 10 01;43:14-29.
    PMID: 27422195 DOI: 10.1016/j.actbio.2016.07.015
    Poly(amidoamine) dendrimers (PAMAM) are well-defined, highly branched, nanoscale macromolecules with numerous active amine groups on the surface. PAMAM dendrimer can enhance the solubility of hydrophobic drugs, and with numerous reactive groups on the surface PAMAM dendrimer can be engineered with various functional groups for specific targeting ability. However, in physiological conditions, these amine groups are toxic to cells and limit the application of PAMAM. In the recent years, polyethylene glycol (PEG) conjugation has been the most widely used approach to reduce the toxicity of the active group on dendrimer surface. PEG molecules are known to be inert, non-immunogenic, and non-antigenic with a significant water solubility. PEGylated PAMAM-mediated delivery could not only overcome the limitations of dendrimer such as drug leakage, immunogenicity, hemolytic toxicity, systemic cytotoxicity but they also have the ability to enhance the solubilization of hydrophobic drugs and facilitates the potential for DNA transfection, siRNA delivery and tumor targeting. This review focuses on the recent developments on the application and influence of PEGylation on various biopharmaceutical properties of PAMAM dendrimers.

    STATEMENT OF SIGNIFICANCE: It is well established that dendrimers have demonstrated promising potentials for drug delivery. However, the inherent toxicity poses challenges for its clinical translation. In this regard, PEGylation has helped mitigate some of the toxicity concerns of dendrimers and have paved the way forward for testing its translational potentials. The review is a collection of articles demonstrating the utility of PEGylation of the most studied PAMAM dendrimers. To our knowledge, this is a first such attempt to draw reader's attention, specifically, towards PEGylated PAMAM dendrimers.

  18. Wickens JM, Alsaab HO, Kesharwani P, Bhise K, Amin MCIM, Tekade RK, et al.
    Drug Discov Today, 2017 Apr;22(4):665-680.
    PMID: 28017836 DOI: 10.1016/j.drudis.2016.12.009
    The cluster-determinant 44 (CD44) receptor has a high affinity for hyaluronic acid (HA) binding and is a desirable receptor for active targeting based on its overexpression in cancer cells compared with normal body cells. The nanocarrier affinity can be increased by conjugating drug-loaded carriers with HA, allowing enhanced cancer cell uptake via the HA-CD44 receptor-mediated endocytosis pathway. In this review, we discuss recent advances in HA-based nanocarriers and micelles for cancer therapy. In vitro and in vivo experiments have repeatedly indicated HA-based nanocarriers to be a target-specific drug and gene delivery platform with great promise for future applications in clinical cancer therapy.
  19. Mansuri S, Kesharwani P, Tekade RK, Jain NK
    Eur J Pharm Biopharm, 2016 May;102:202-13.
    PMID: 26563727 DOI: 10.1016/j.ejpb.2015.10.015
    Dendrimers are multifunctional carriers widely employed for delivering drugs in a variety of disease conditions including HIV/AIDS and cancer. Albendazole (ABZ) is a commonly used anthelmintic drug in human as well as veterinary medicine. In this investigation, ABZ was formulated as a "muco-dendrimer" based sustained released tablet. The mucoadhesive complex was synthesized by anchoring chitosan to fifth generation PPI dendrimer (Muco-PPI) and characterized by UV, FTIR, (1)H NMR spectroscopy and electron microscopy. ABZ was entrapped inside Muco-PPI followed by lyophilization and tableting as matrix tablet. A half-life (t1/2) of 8.06±0.15, 8.17±0.47, 11.04±0.73, 11.49±0.92, 12.52±1.04 and 16.9±1.18h was noted for ABZ (free drug), conventional ABZ tablet (F1), conventional ABZ matrix tablet (F2), PPI-ABZ complex, PPI-ABZ matrix tablet (F3) and Muco-PPI-ABZ matrix tablet (F4), respectively. Thus the novel mucoadhesive-PPI based formulation of ABZ (F4) increased the t1/2 of ABZ significantly by almost twofold as compared to the administration of free drug. The in vivo drug release data showed that the Muco-PPI based formulations have a significantly higher Cmax (2.40±0.02μg/mL) compared with orally administered free ABZ (0.19±0.07μg/mL) as well as conventional tablet (0.20±0.05μg/mL). In addition, the Muco-PPI-ABZ matrix tablet displayed increased mean residence time (MRT) and is therefore a potential candidate to appreciably improve the pharmacokinetic profile of ABZ.
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