Kifayat Ullah Shah

Co-delivery strategies to overcome multidrug resistance in ovarian cancer

Cancer is one of the leading causes of death and equally strikes both genders. Among women, ovarian cancer is responsible for many deaths as it remains symptomless in the earlier stages and generally diagnosed in third stage. At this point it becomes difficult to carry out de-bulking surgery and treatment with different chemotherapeutic drugs has shown resistance, a phenomenon known as multidrug resistance (MDR). Different treatment choices are available for ovarian cancer; however, this article only focuses on various co-delivery strategies, where two different agents are encapsulated in a single carrier and act via different pathways to overcome cancer cell resistance. Ovarian cancer develops MDR via different pathways but majorly involving pump and the non-pump mechanisms in most cases. To overcome MDR it is imperative to strike malignant cells from various directions. Nanocarriers are known to strike the pump mechanism by avoiding the drug efflux pump located on cellular membrane. The efflux pump can also be blocked by blocking activity of ATP binding cassette (ABC) membrane transporters. To stop the non-pump mechanism one can use chemosensitizers, genes, apoptotic factor and others. Treatment of cancer cells could even more effective if the drug is combined with co-agents in a single carrier with targeting moiety. These co-agents along with nanocarriers, allow the drug to accumulate in high enough concentrations in ovarian cancer cells to kill them without affecting normal cells.

Nigella sativa provides protection against metabolic syndrome

The seeds of Nigella sativa have been used in folk medicine all over the world. The plant has been of interest due to its low degree of toxicity and beneficial pharmacological properties like antihypertensive, hypoglycemic, antifungal, anti-inflammatory, antihistaminic, antioxidant, along with significant anti-neuplastic activities. The present clinical study was undertaken to ascertain the adjuvant effect of Nigella seeds on various clinical and biochemical parameters of metabolic syndrome. After final diagnosis and considering inclusion and exclusion criteria, one hundred and fifty nine patients were enrolled in this study. Patients were divided into two groups. In Group I (standard group), patients were advised to take simvastatin 10 mg once a day, metformin 500 mg twice a day, Enalapril 10 mg once a day, Atenolol 50 mg once a day and clopidagrel 75 mg once a day for a period of six weeks. In Group II ( Nigella seeds group), patients were advised the above standard medication plus Nigella seeds 250 mg twice daily for a period of six weeks. Blood sugar both fasting and postprandial, fasting lipid profile and different parameters of obesity were recorded before therapy and after completion of therapy. It was found that the addition of Nigella seeds provide beneficial effects in all the clinical and biochemical parameters for the adult’s treatment panel-III of metabolic disorders especially in fasting blood sugar, low density lipoproteins and high density lipoproteins. No sign of toxicity of the plant appeared in the Group II. Improvement in all other parameters like blood pressure, circumference of waist and serum triglyceride was also observed. Thus, Nigella seeds were found to be effective as an adjuvant therapy in patients of dyslipidemia and hyperglycemia. Keywords: Nigella sativa , toxicity, hyperglycemia, adjuvant, antihistaminic, antioxidant, patients

Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37°C ± 0.1. Similarity factor f 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including C max⁡, T max⁡ and AUC0-t were compared which showed an optimized C max⁡ and T max⁡ (P < 0.05). A good correlation was obtained between in vitro drug release and in vivo drug absorption with correlation value (R 2 = 0.934). Relative bioavailability was found to be 93%. Reproducibility of manufacturing process and accelerated stability of the developed tablets were performed in stability chamber at 40 ± 2°C and 75 ± 5% relative humidity for a period of 6 months and were found to be stable throughout the stability period.

Once daily controlled release matrix tablet of Prochlorperazine maleate: Influence of Ethocel® and/or Methocel® on in vitro drug release and bioavailability

Context: Controlled release (CR) matrix tablet of Prochlorperazine maleate was developed to improve its patient compliance. Methods: Tablet formulations F1, F2 and F3 based on different concentrations of Methocel® K100 LV-CR Premium, were compacted by direct compression method while tablet formulations F4, F5 and F6, based on distinct blends of Methocel® K100 LV-CR Premium and Ethocel® Standard 7FP Premium, were compressed by flow-bound dry granulation-slugging method. The prepared powder mixtures, granules and tablets were evaluated for their physicochemical performance. Bioequivalence study of the optimized test tablet versus reference-conventional Stemitil® tablet was conducted on rabbits, using HPLC-UV system at λmax 254 nm. Results: The test tablet, containing 28% Methocel® and 58% Ethocel® (F6) exhibited desired zero order kinetics for 24 h and was found stable at accelerated storage conditions for 6 months. In vitro drug release rate decreased as the Ethocel® content in the blend was increased, perhaps due to slower penetrability of water. Hydrodynamic conditions and hardness of tablets could not affect drug release kinetics. The tablet displayed significantly (p < 0.05) optimized peak drug concentration-Cmax (45 ± 3.42 vs. 64.5 ± 4.03), extended half life-t1/2 (16.071 ± 3.97 vs. 5.257 ± 1.314 h) and bioequivalence to the reference tablet taken three times a day (1409 ± 15 ng·h/mL vs. 1346 ± 23 ng h/mL). The tablet showed strong Level A correlation (R2 = 0.8458) between drug absorbed in vivo and drug released in vitro. Conclusions: The developed tablet may be adopted by pharmaceutical industry to improve patient compliance of the Prochlorperazine maleate.

Release pattern of three new polymers in Ketoprofen controlled-release tablets

The objective of the study was to formulate and evaluate sustained release polymeric tablets of ketoprofen for the release rate, release patterns and the mechanism involved in the release process of the drug. Formulations with three different types of newly synthesized polymers and one grade of ethyl cellulose ether derivatives (FP100 premium) in several drug-to-polymer ratios (D:P ratio 10:1, 10:2 and 10:3) were compressed into tablets using the direct compression method. They were examined for their physical properties and appearance. Tablets dimensional tests (thickness, diameter) and Q.C tests (hardness, friability, disintegration) were performed according to the USP methods. For in vitro drug release studies of Ketoprofen controlled release (CR) tablets, the USP Method-1 (Rotating Basket Method) was used with Pharma test dissolution apparatus (D-63512 Hainburg, Germany). The medium used for dissolution was phosphate buffer having a pH of 7.4 kept at constant temperature of 37±1°C. In order to analyze the drug release kinetics from each of the prepared matrices, five different mathematical models were applied to the release data including zero order kinetics, first order kinetics, Higuchi kinetics, Hixson Crowell kinetics and Korsmeyer Peppas equations were applied to the release data. The results obtained from different parameters showed that polymers: Polyglycolide, PGA-cocaprolactone, PGA-co-pentadecalactone and Ethocel FP100 premium can be used successfully in order to develop directly compressed prolonged release tablets of slightly soluble drugs such as ketoprofen. Particle size of polymer is a determining factor in controlling the release of ketoprofen from tablets. Ethocel standard FP100 polymers extend the release rates of drug more efficiently than the conventional granular form of the other three polymers. Further, the three new polymers and Ethocel FP100 could efficiently extend the release of the drugs as compared to the reference conventional formulation.

From nanoemulsions to self-nanoemulsions, with recent advances in self-nanoemulsifying drug delivery systems (SNEDDS)

ABSTRACT Introduction: Lipid-based drug delivery systems (LBDDS) are the most promising technique to formulate the poorly water soluble drugs. Nanotechnology strongly influences the therapeutic performance of hydrophobic drugs and has become an essential approach in drug delivery research. Self-nanoemulsifying drug delivery systems (SNEDDS) are a vital strategy that combines benefits of LBDDS and nanotechnology. SNEDDS are now preferred to improve the formulation of drugs with poor aqueous solubility. Areas covered: The review in its first part shortly describes the LBDDS, nanoemulsions and clarifies the ambiguity between nanoemulsions and microemulsions. In the second part, the review discusses SNEDDS and elaborates on the current developments and modifications in this area without discussing their associated preparation techniques and excipient properties. Expert opinion: SNEDDS have exhibit the potential to increase the bioavailability of poorly water soluble drugs. The stability of SNEDDS is further increased by solidification. Controlled release and supersaturation can be achieved, and are associated with increased patient compliance and improved drug loads, respectively. Presence of biodegradable ingredients and ease of large-scale manufacturing combined with a lot of ‘drug-targeting opportunities’ give SNEDDS a clear distinction and prominence over other solubility enhancement techniques.

A Homozygous Missense Mutation in SLC25A16 is Associated with Autosomal Recessive Isolated Fingernail Dysplasia in a Pakistani Family

Developmental nail disorders are heterogeneous group of genodermatosis, with nonsyndromic congenital nail disorder (NDNC) being a rare subgroup inherited in autosomal dominant or autosomal recessive pattern. These are classified into ten different types (NDNC1-10), which are described in OMIM.1 The genes described for isolated nail disorders include PLCD1 (MIM 602142), RSPO4 (MIM 610573), FZD6 (MIM 603409), COL7A1 (MIM 120120), HPGD (MIM 601688) and SLCO2A1 (MIM 601460). In Addition, two other loci for NDNC have been mapped on chromosome 17p13 and 17q25.1-17q25.3.1, 2 This article is protected by copyright. All rights reserved.

Thiomers and their potential applications in drug delivery

ABSTRACT Introduction: Thiomers are the product of the immobilization of sulfhydryl-bearing ligands onto the polymer backbone of a conventional polymer, which results in a significant improvement in mucoadhesion; in situ gelation and efflux inhibition compare with unchanged polymers. Because of thiol groups, thiomers have more reactivity and enhanced protection against oxidation. Since the late 1990s, extensive work has been conducted on these promising polymeric excipients in the pharmaceutical field. Areas covered: This review covers thiomers, their classification and their different properties. Various techniques for the synthesis, purification and characterization of thiomers are described in detail. This review also encompasses their various properties such as mucoadhesion, permeation enhancement, in situ gelation and efflux inhibition, as well as different formulations based on thiomers. In addition to the use of thiomers as multifunctional excipients, this review also encompasses their use as drugs. Expert opinion: The synthesis is realized by linkage of sulfhydryl-bearing ligands but reported methods give low yields. Higher degrees of modification are not necessary and would probably lead to extreme changes in properties. Nevertheless, an accurate characterization of the final product is important. The scale-up procedure for industrial manufacturing has been adapted to produce GMP materials; Lacrimera® eye drops have already entered the European market.

Functionalised nanostructures for transdermal delivery of drug cargos

Abstract Nanotechnology has burgeoned over last decade exploring varieties of novel applications in all areas of science and technology. Utilisation of bio-friendly polymers for engineering nanostructures (NS) improves safety and efficacy in drug delivery. Biopolymers not merely employed for fabricating drug carriers but also leveraged for surface functionalisation of other NS to impart bio-mimicking properties. Biopolymer functionalised NS garnered researcher’s attention because of their potential to enhance skin permeability of drug cargo. Biopolymers, i.e. cell-penetrating peptides (CPP), chitosan and hyaluronic acid not only enhance skin permeability but also add multiple functions due to their intrinsic biomimetic properties. This multifunctional drug delivery system is a promising tool to achieve skin delivery of large number of therapeutic agents. In this review, functionalisation of NS with biopolymers particularly polysaccharides and polypeptides is discussed in detail. In particular, applications of these functionalised NS for TDDS is elaborated. Moreover, this review provides framework for elaborating importance of functionalisation of NS to enhance skin permeability and depicts advantages of biopolymers to construct more biocompatible carriers for drug cargos.

Factors associated with anxiety in type 2 diabetes mellitus patients in Pakistan

The aim of this study was to assess the factors associated with anxiety in type 2 diabetes mellitus patients (T2DM) by using Hamilton Anxiety Rating Scale (HAM-A). A cross-sectional quantitative study was conducted after necessary ethical approval from Medicare Hospital Rawalpindi and Capital Development Authority Hospital Islamabad in accordance with Declaration of Helsinki. Three hundred thirty-eight patients with type 2 diabetes mellitus were selected by non-stratified random sampling technique from August 2016 to February 2017. Majority of the T2DM patients (n = 258, 66.5%) had mild anxiety, followed by mild to moderate anxiety (n = 82, 21.1%). A significant association (p < 0.01) was observed between anxiety and patients’ gender, education, and occupation; whereas, statistically insignificant association (p > 0.05) was observed between HAM-A score and patients’ age, family history, and life style. Linear regression analysis revealed gender (OR = − 0.308, CI-0.57-0.299) as a significant predictor (p < 0.01) for anxiety. Findings of this study demonstrate that large proportion of the diabetic patients is suffering with type of anxiety. A significant association of anxiety was identified with gender, education, and occupation of type 2 diabetes patients.