Frequency: Quarterly E- ISSN: 2250-0243 P- ISSN: 2249-3530 IBI Factor 3.9 Abstracted/ Indexed in: Ulrich's International Periodical Directory, Google Scholar, SCIRUS, Genamics Journal Seek, PSOAR, getCITED, InfoBase Index, EBSCO Information Services
Quarterly published in print and online "Inventi Impact: Advanced Dosaging" publishes high quality unpublished as well as high impact pre-published research and reviews catering to the needs of researchers and professionals. This journal focuses on finding the newer methods of administering active pharmaceuticals to the patients either through newer dosage forms of by deploying newer administration devices. The first of its kind of journal, "Inventi Impact: Advanced Dosaging" invites researchers sharing new insight in achieving the therapeutic goals.
Microneedle (MN) technology is an optimal choice for the delivery of drugs via the transdermal route, with a minimally invasive procedure. MN applications are varied from drug delivery, cosmetics, tissue engineering, vaccine delivery, and disease diagnostics. The MN is a biomedical device that offers many advantages including but not limited to a painless experience, being time-effective, and real-time sensing. This research implements additive manufacturing (AM) technology to fabricate MN arrays for advanced therapeutic applications. Stereolithography (SLA) was used to fabricate six MN designs with three aspect ratios. The MN array included conical-shaped 100 needles (10 × 10 needle) in each array. The microneedles were characterized using optical and scanning electron microscopy to evaluate the dimensional accuracy. Further, mechanical and insertion tests were performed to analyze the mechanical strength and skin penetration capabilities of the polymeric MN. MNs with higher aspect ratios had higher deformation characteristics suitable for penetration to deeper levels beyond the stratum corneum. MNs with both 0.3 mm and 0.4 mm base diameters displayed consistent force–displacement behavior during a skin-equivalent penetration test. This research establishes guidelines for fabricating polymericMNfor high-accuracy and low-cost 3D printing....
A Bayesian adaptive design for dose finding of a combination of two drugs in cancer phase I clinical trials that takes into account\npatients heterogeneity thought to be related to treatment susceptibility is described. The estimation of the maximum tolerated dose\n(MTD) curve is a function of a baseline covariate using two cytotoxic agents. A logistic model is used to describe the relationship\nbetween the doses, baseline covariate, and the probability of dose limiting toxicity (DLT). Trial design proceeds by treating cohorts\nof two patients simultaneously using escalation with overdose control (EWOC), where at each stage of the trial, the next dose\ncombination corresponds to the.................
Background: The addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first\r\nline treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and\r\nactivity of a lower dose of bevacizumab in pretreated advanced stage EOC.\r\nMethods: We treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior\r\ncytotoxic regimens, with bevacizumab 5ââ?¬â??7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral\r\ncyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor\r\nresponse was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT.\r\nResults: The median number of bevacizumab cycles was 21 (range 3ââ?¬â??59). The median baseline CA125 was 272 U/\r\nml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial\r\nresponse (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 ââ?¬â?? 95.8) according\r\nto Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall\r\nmetabolic response rate of 67% (95%CI, 42.8 ââ?¬â?? 90.6) according to PET Response Criteria in Solid Tumors (PERCIST).\r\nMedian progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3\r\nadverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment\r\nwas delayed in five patients for nasal bleeding or uncontrolled hypertension.\r\nConclusions: Low-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated\r\npopulation of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC....
Background.Many studies have demonstrated that a higher radiotherapy dose is associated with improved outcomes in non-smallcell\nlung cancer (NSCLC). We performed a dosimetric planning study to assess the dosimetric feasibility of intensity-modulated\nradiation therapy (IMRT) with a simultaneous integrated boost (SIB) in locally advanced NSCLC. Methods. We enrolled twenty\npatients. Five different dose plans were generated for each patient. All plans were prescribed a dose of 60Gy to the planning tumor\nvolume (PTV). In the three SIB groups, the prescribed dose was 69Gy, 75Gy, and 81Gy in 30 fractions to the internal gross tumor\nvolume (iGTV). Results. The SIB-IMRT plans were associated with a significant increase in the iGTV dose (P < 0.05), without\nincreased normal tissue exposure or prolonged overall treatment time. Significant differences were not observed in the dose to the\nnormal lung in terms of the V5 and V20 among the four IMRT plans.The maximum dose (Dmax) in the esophagus moderately\nincreased along with the prescribed dose (P < 0.05). Conclusions. Our results indicated that escalating the dose by SIB-IMRT is\ndosimetrically feasible; however, systematic evaluations via clinical trials are still warranted. We have designed a further clinical\nstudy (which is registered with ClinicalTrials.gov, number NCT02841228)....
Background\nWe have harnessed a novel biological system, the bacterial minicell, to deliver cancer therapeutics\nto cancer cells. Preclinical studies showed that epidermal growth factor receptor\n(EGFR)-targeted, paclitaxel-loaded minicells (EGFRminicellsPac) have antitumor effects in\nxenograft models. To examine the safety of the minicell delivery system, we initiated a firsttime-\nin-human, open-label, phase I clinical study of EGFRminicellsPac in patients with\nadvanced solid tumors.\nMethodology\nPatients received 5 weekly infusions followed by a treatment free week. Seven dose levels\n(1x108, 1x109, 3x109, 1x1010, 1.5x1010, 2x1010, 5x1010) were evaluated using a 3+3 doseescalation\ndesign. Primary objectives were safety, tolerability and determination of the maximum\ntolerated dose. Secondary objectives were assessment of immune/inflammatory\nresponses and antitumor activity.\nPrincipal Findings\nTwenty eight patients were enrolled, 22 patients completed at least one cycle of EGFR mini cells Pac;\n6 patients did not complete a cycle due to rapidly progressive disease. A total of\n236 doses was delivered over 42 cycles, with a maximum of 45 doses administered to a single\npatient. Most common treatment-related adverse events were rigors and pyrexia. No\ndeaths resulted from treatment-related adverse events and the maximum tolerated dose\nwas defined as 1x1010 EGFR mini cells Pac. Surprisingly, only a mild self-limiting elevation in the inflammatory cytokines IL-6, IL-8 and TNF�± and anti-inflammatory IL-10 was observed.\nAnti-LPS antibody titers peaked by dose 3 and were maintained at that level despite repeat\ndosing with the bacterially derived minicells. Ten patients (45%; n = 22) achieved stable disease\nas their best response.\nConclusions/Significance\nThis is the first study in humans of a novel biological system that can provide targeted delivery\nof a range of chemotherapeutic drugs to solid tumor cells. Bispecific antibody-targeted\nminicells, packaged with the chemotherapeutic paclitaxel, were shown to be safe in patients\nwith advanced solid tumors with modest clinical efficacy observed. Further study in Phase II\ntrials is planned....
Background: The prevalence of asthma has increased over recent decades and the reasons for this are poorly\r\nunderstood. A sensitive tool that can evaluate potential risk factors for asthma is bronchial hyperresponsiveness\r\n(BHR), a key physiological characteristic of asthma. However, although the minimum clinically important difference\r\nin BHR for an individual is accepted to be around one doubling dose, the minimum important change in a\r\npopulation is not defined. As with surrogate measures of cardiovascular disease risk such as blood pressure and\r\ncholesterol, a change that is not clinically important in an individual may be extremely important in public health\r\nterms.\r\nFindings: To assess the potential impact of a small absolute change in BHR across a population, we modelled the\r\neffect of different changes in BHR on the prevalence rates of moderate and severe BHR in an asthmatic population.\r\nWe calculate that a one half doubling dose increase in BHR increases the prevalence of moderate and severe BHR\r\nby 30%. If this was accompanied by an equivalent increase in the population prevalence of moderate and severe\r\nasthma, this would be highly significant in public health terms.\r\nConclusions: We propose that a one half doubling dose worsening in BHR across a population may represent an\r\nimportant change...
A liposome formulation for paclitaxel was developed in this study. The liposomes, composed of naturally unsaturated and hydrogenated phosphatidylcholines, with significant phase transition temperature difference, were prepared and characterized. The liposomes exhibited a high content of paclitaxel, which was incorporated within the segregated microdomains coexisting on phospholipid bilayer of liposomes. As much as 15% paclitaxel to phospholipid molar ratio were attained without precipitates observed during preparation. In addition, the liposomes remained stable in liquid form at 4�°C for at least 6 months. The special composition of liposomal membrane which could reduce paclitaxel aggregation could account for such a capacity and stability. The cytotoxicity of prepared paclitaxel liposomes on the colon cancer C-26 cell culture was comparable to Taxol. Acute toxicity test revealed that LD50 for intravenous bolus injection in mice exceeded by 40?mg/kg. In antitumor efficacy study, the prepared liposomal paclitaxel demonstrated the increase in the efficacy against human cancer in animal model. Taken together, the novel formulated liposomes can incorporate high content of paclitaxel, remaining stable for long-term storage. These animal data also demonstrate that the liposomal paclitaxel is promising for further clinical use....
We have developed a new ââ?¬Å?drugââ?¬Â and approach that appear to be effective in reducing arterial age. This ââ?¬Å?drugââ?¬Â represents a\nlow, subtherapeutic dose of statin and sartan and particularly their low-dose combination. The improvement of arterial wall\ncharacteristics, also reflecting in a decrease of arterial age, was achieved after a short period of treatment (one month) with the\nabove-mentioned drugs. In addition, we have also implemented a new, innovative therapeutic approach, consisting of intermittent\n(cyclic) treatmentââ?¬â?alternating short ââ?¬Å?treatmentââ?¬Â periods andmuch longer ââ?¬Å?restââ?¬Â periods (when the beneficial effects are still present\nbut gradually decline). This new ââ?¬Å?drugââ?¬Â and approach both merit further investigation in order to confirm their antiaging efficacy....
Combination of chemotherapy and immunotherapy has been a promising strategy in cancer\ntreatment. Polysaccharides from Angelica sinensis (AP), a well-known Chinese herbal medicine,\nhave been proved to have good immunomodulatory activity. In the present study, an enzyme-sensitive\ntumor-targeting nano drug delivery system (AP-PP-DOX (doxorubicin), PP stood for peptide)\nwas constructed. In this system, Angelica polysaccharides act as not only carriers to targeted\ndelivery of drugs to tumor tissue but also eectors to improve tumor microenvironment and enhance\nimmune function, resulting in synergistic antitumor eect with chemotherapy drugs. The structure\nof this conjugate was confirmed by FI-IR and 1H-NMR. The particle size and zeta potential of\nthe nanoparticles were...................................................................................................
Limitations of bone defect reconstruction include poor bone healing and osteointegration with acrylic cements, lack of strength with bone putty/paste, and poor osteointegration. Tissue engineering aims to bridge these gaps through the use of bioactive implants. However, there is often a risk of infection and biofilm formation associated with orthopedic implants, which may develop anti-microbial resistance. To promote bone repair while also locally delivering therapeutics, 3D-printed implants serve as a suitable alternative. Soft, nanoporous 3D-printed filaments made from a thermoplastic polyurethane and polyvinyl alcohol blend, LAY-FOMM and LAY-FELT, have shown promise for drug delivery and orthopedic applications. Here, we compare 3D printability and sustained antibiotic release kinetics from two types of commercial 3D-printed porous filaments suitable for bone tissue engineering applications. We found that both LAY-FOMM and LAY-FELT could be consistently printed into scaffolds for drug delivery. Further, the materials could sustainably release Tetracycline over 3 days, independent of material type and infill geometry. The drug-loaded materials did not show any cytotoxicity when cultured with primary human fibroblasts. We conclude that both LAY-FOMM and LAY-FELT 3D-printed scaffolds are suitable devices for local antibiotic delivery applications, and they may have potential applications to prophylactically reduce infections in orthopedic reconstruction surgery....
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