Ziyaur Rahman

Nanomedicines as cancer therapeutics: current status.

As of 21st century, cancer is arguably the most complex and challenging disease known to mankind and an inevitable public health concern of this millennium. Nanotechnology, suitably amalgamated with cancer research, has ushered an era of highly personalized and safer medicines which can improve cancer diagnosis and therapy. A wide variety of nanomedicines are currently under investigation, including polymeric/non-polymeric nanoparticles, dendrimers, quantum dots, carbon nanotubes, lipid- and micelle-based nanoparticles. The bases of these nanomedicines in reducing toxicity associated with cancer therapy are their ability to carry a large payload and multivalent-ligand targeting. This imparts specificity for targeting the tissues as well as bypass resistance mechanisms. The major hurdles on these future medicines are potential toxicity of nanoparticles, which imposes the need of extensive regulatory evaluation before nanomedicines could be utilized as cancer therapeutics. This review highlights nanopharmaceuticals that have been investigated in oncology for various applications (diagnosis, therapeutic delivery and theranostics). It also discusses the effects of nano-sized materials on tissues/organ functions, the possibility of overcoming multi-drug resistance by using nanomedicines and their current clinical status.

Nanometric gold in cancer nanotechnology: current status and future prospect

This review elaborate on modified gold nanoparticulate concept in oncology, provides an overview of the use of gold nanoparticles in cancer treatment and discusses their potential applications and clinical benefits.

Omega-3 fatty acids as pharmacotherapeutics in psoriasis: current status and scope of nanomedicine in its effective delivery.

Psoriasis is a multifactorial autoimmune skin disorder based on irregularities of the T- cell function. The abnormal keratinocyte hyper proliferation in psoriasis arises due to the activation of T-cells which produces rich amount of arachidonic acid leads to generation of various proinflammatory mediators like PGs, LTs, cytokines and adhesion molecules via MAPK/AP-1, EARK1/2 and protein kinase-C (PKCs) activation pathways. Incorporation of naturally occuring bioactives like, omega (ω)-3 fatty acids (i.e., EPA and DHA) in a dose dependent manner results in inhibition of various pro-inflammatory mediators and metabolization of EPA and DHA leads to dampening of inflammation and higher resolution of the skin abnromalities. These all due to the promotion of the synthesis of ω-3 PUFA-derived lipid mediators viz namely resolvins and protectins. These have been widely used alone or in combination with other drugs in the treatment of psoriasis. Despite of their meritorious visages, the use of these bioactives is associated with several hiccups like higher unstability and vulnerable to degradation due to lipid peroxidation, poor and incosistent bioavilability by oral and topical administration. The potential use of nanomedicines in the delivery of such bioactives has gained wider attention owing to their promising bioavailability enhancement characteristics, improved stability and better efficacy. The present review gives an extensive account on ω-3 fatty acids (EPA and DHA) starting from seedling to apex, including biosynthesis, metabolites, and its mechanism of action in psoriasis. Moreover, barriers in the effective delivery of ω-3 fatty acids and how nanomedicines can be fit in the scope of its therapeutic delivery in psoriasis have also been addressed. Despite numerous advantages, application of EPA-DHA as ω-3 fatty acids therapeutics in the management of psoriasis are still at an initial stage. Nanomedicines approach to achieve high bioavailable delivery with safety and stability of ω-3 fatty acids showing the promising area for the future in psoriasis management.

Development of meloxicam in situ implant formulation by quality by design principle

Abstract Objective: The focus of this study was to develop and optimize in situ implant formulation of meloxicam by quality by design (QbD) principle for long-term management of musculoskeletal inflammatory disorders. Methods: The formulation was optimized by Box–Behnken design with polylactide-co-glycolide (PLGA) level (X1), N-methyl pyrrolidone level (X2) and PLGA intrinsic viscosity (X3) as the independent variables and initial burst release of drug (Y1), cumulative release (Y2), and dissolution efficiency (Y3) as the dependent variables. The formulation was physicochemically characterized by scanning electron microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy and powder X-ray diffraction (PXRD). Pharmacokinetic studies of the optimized formulation were performed on Sprague--Dawley rats. Results: Y1 was significantly affected by X2 and X3. Y2 was affected by X1 and X3 while Y3 was affected by all three independent variables employed in the formulations. Responses for the optimized formulation were in close agreement with the values predicted by the model. SEM photomicrographs indicated uniform gel formulation. No chemical interaction between the components of formulation was observed by FT-IR and meloxicam was found to be present in the amorphous form in the gel matrix as revealed by PXRD. The maximum plasma concentration (Cmax), time to achieve Cmax and area under plasma concentration curve were significantly different from those of the solution formulation used as the control. Plasma concentration of meloxicam was maintained above its IC50 concentration required for COX-2 inhibition for 23 days. Conclusion: Meloxicam in situ implant may provide long-term management of inflammatory conditions with improved patient compliance and better therapeutic index.

Ocular pharmacoscintigraphic and aqueous humoral drug availability of ganciclovir-loaded mucoadhesive nanoparticles in rabbits

Abstract The present report describes the improved ocular retention and aqueous humoral drug availability of ganciclovir (GCV) when administered via topical instillation of different kind of nanoparticles onto the rabbit eye. GCV was loaded into PLGA nanoparticles, chitosan-coated nanoparticles and chitosan-coated niosomal nanoparticles. All three formulations contained nanoparticles equally round in shape with a mean particle size in the range of 180–200 nm. The ocular corneal retention property was evaluated by gamma scintigraphy, revealing that the clearance was slowest in the case of the chitosan-containing formulations. GCV in chitosan-coated PLGA nanoparticles and chitosan-coated niosomal nanoparticles showed approx. 6-fold higher aqueous humor drug availability as compared to a GCV solution and nearly 2.5-fold higher as compared to the chitosan-lacking GCV-PLGA nanoparticles. The results indicate that the use of a mucoadhesive chitosan coating can improve the ocular residence time and aqueous humoral availability of GCV when administered topically in nanoparticles.

Role of Nanomedicines in Delivery of Anti-Acetylcholinesterase Compounds to the Brain in Alzheimer’s Disease

Alzheimers disease (AD) is a multifarious progressive neuro-degenerative state among elders. Potentiation of central cholinergic activity by using acetylcholinesterase inhibitors (AChEI) is considered as one of the major pharmacological means for the management of AD. Investigation in the past and the rest decades revealed that many drugs with anti-AD activity, including the AChEI have been discovered from natural and synthetic origin but getting success in their brain delivery is still limited. However, barriers like blood-brain barrier, blood-cerebrospinal fluid barrier and p-glycoproteins restrict the effective and safe drug delivery to the brain in patients with AD. Advancement in nanotechnology-based drug delivery systems over the last decade exemplifies the effective drug delivery and targeting to the brain with controlled rate in various diseases including AD. Till recently, diverse kinds of nanomedicines for targeting of the anti-AD drugs in brain are being studied. In this review, we have highlighted the recent progress in AChEI, challenges in their effective brain delivery (physicochemical properties and biological barriers) and possible nanotechnology-based strategies that can deliver drugs across the CNS barriers during AD.

Nanotechnology to Combat Multidrug Resistance in Cancer

Multidrug resistance (MDR) in cancer is a prime obstacle toward successful cancer chemotherapy which is the combination of the complicated mechanisms involving abnormal vasculature, localized area of hypoxia, upregulated ABC transporters, aerobic glycolysis, elevated apoptotic threshold, and increased interstitial fluid pressure. Nanomedicines in targeted cancer chemotherapy hold great promise as an effective approach to prevail over MDR. Extensive research has been conducted to get success in development of Nanomedicines against MDR that introduced many of them as personalized medicine and in different clinical stages. Nanomedicines can be preferentially accumulated in tumor areas by EPR and by active targeting of upregulated processes such as ABC transporters of cancer cells. In this review, we aimed to discuss different nanomedicines that showed promises against MDR in cancer and improved the chemotherapeutic efficacy in the last decade. Moreover, different cellular and physiological factors that underlie MDR in cancer will also be discussed.

Tulsi oil as a potential penetration enhancer for celecoxib transdermal gel formulations.

Abstract The focus of the present study was to develop and evaluate the transdermal system of celecoxib. Transdermal gels composed of carbopol 940 in propylene glycol (PG) containing penetration enhancers. The formulations were characterized by permeation, pharmacokinetics, pharmacodynamics and histopathology. Celecoxib permeation across excised rat skins were statistically (p < 0.05) enhanced by tulsi oil compared to turpentine oil containing formulations. In comparison to orally administered formulations, the pharmacokinetic parameters of gel and control formulations were significantly higher (p < 0.05). The maximum plasma concentration (Cmax) obtained with formulations containing 4% turpentine and 6% tulsi oil was, respectively, 1.52 and 2.41 times higher than the formulations without penetration enhancer. Similarly, area under the curve (AUC) of these formulations was 1.70 and 2.40 times higher than the formulations without penetration enhancers. Anti-inflammatory studies demonstrated a statistically significant (p < 0.05) pharmacodynamics profile for the transdermal gel formulations compared to orally administered and control celecoxib formulations. Histopathological studies revealed some disruption in the epidermis without any toxic effect on the dermis layer of skin by penetration enhancers. In summary, the transdermal gel formulations of celecoxib containing penetration enhancers sustained drug level in the blood and will reduce the dose frequency as required with its conventional oral formulation.

Quantitative estimation of phenytoin sodium disproportionation in the formulations using vibration spectroscopies and multivariate methodologies

Phenytoin sodium (PS) has a tendency to convert to its base form; phenytoin base (PHT) during manufacturing, packaging, shelf life and in-use conditions that can influence its clinical performance. The objective of the present work was to develop a non-destructive, quick and easy analytical method for quantification of PHT in the drug product. A formulation was prepared to contain the excipients of commercial capsule formulation of PS. The formulation containing either 100% PHT or PS was prepared and these formulations were mixed in different proportion to achieve 0-100% PHT matrices. FTIR, NIR and Raman spectra of samples were collected. Data were truncated and mathematically pretreated before development of partial least squares (PLS) and principal component analysis (PCA) regressions model. The models were assessed by slope, intercept, R, R2, root mean square error (RMSE) and standard error (SEP). The models exhibited good linearity over the selected range of PHT in the formulations with low error as indicated by slope that was close to one and small values of intercept, RMSE and SE. The models of NIR based data were more accurate and precise than Raman data based models as indicated by the low values of RMSE and SE. Prediction accuracy of independent samples containing 25% PHT using NIR models were similar to Raman models. On the other hand, the prediction was more precise for the independent sample containing 5% PHT using NIR data based models compared to Raman data based models as indicated by standard deviation. In conclusion, chemometric models based on NIR and Raman spectroscopies provides a fast and easy way to monitor the disproportionation of PS in the drug products.

Sample Size for Tablet Compression and Capsule Filling Events During Process Validation

During solid dosage form manufacturing, the uniformity of dosage units (UDU) is ensured by testing samples at 2 stages, that is, blend stage and tablet compression or capsule/powder filling stage. The aim of this work is to propose a sample size selection approach based on quality risk management principles for process performance qualification (PPQ) and continued process verification (CPV) stages by linking UDU to potential formulation and process risk factors. Bayes success run theorem appeared to be the most appropriate approach among various methods considered in this work for computing sample size for PPQ. The sample sizes for high-risk (reliability level of 99%), medium-risk (reliability level of 95%), and low-risk factors (reliability level of 90%) were estimated to be 299, 59, and 29, respectively. Risk-based assignment of reliability levels was supported by the fact that at low defect rate, the confidence to detect out-of-specification units would decrease which must be supplemented with an increase in sample size to enhance the confidence in estimation. Based on level of knowledge acquired during PPQ and the level of knowledge further required to comprehend process, sample size for CPV was calculated using Bayesian statistics to accomplish reduced sampling design for CPV.