Development and characterization of polyamidoamine based doxorubicin loaded polymeric nanocarriers and in-vitro evaluation on liver cancer cell lines.

In order to achieve the benefits of targeted drug delivery, this study intended to encapsulate doxorubicin in a linear polyamidoamine and its PEGylated co-polymer. The drug was loaded by using the emulsion solvent evaporation method. By adjusting the doxorubicin to polymer ratios to 1:10, 1:20 and 1:30, three formulations of each polymer/copolymer were prepared. The drug release profile was investigated using phosphate buffered saline. In vitro cytotoxicity investigation was executed on liver cancer cell line (Hep G2 cell lines) by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay. The outcome demonstrated that doxorubicin had been successfully loaded on polyamidoamine and its PEGylated co-polymer with a drug loading efficiency of about 90%. Nanocarrier sizes were between 245±1.10 nm -579±1.00 nm and the zeta potential range was +22.4±0.5 mV-+37.9±0.3 mV. In-vitro drug release investigations revealed a characteristic pH-dependent drug release. The cytotoxicity testing of optimal formulation revealed that the doxorubicin was successfully released from the formulations and exerted therapeutic effect. According to our research, doxorubicin could be loaded onto linear polyamidoamines for potent antitumor effects on the target liver cancer cell lines (Hep G2).

Public awareness regarding the manufacturer provided information about medicine usage, safety, and adverse drug reactions in Balochistan, Pakistan.

Objectives: This study aimed to analyze the general public's awareness of medicine information, safety, and adverse drug reactions in Quetta, Pakistan. Methods: A cross-sectional descriptive study was conducted using random sampling from April 2020 to April 2021 in Quetta. Samples were collected from respondents who met the inclusion criteria and had visited community pharmacies. The analysis was done using SPSS version 23. Bivariate and multivariate analyses were performed to assess factors associated with good knowledge. Results: Multivariate analysis revealed that purchase on prescription was a determining factor of knowledge regarding knowledge of pharmaceutical products and their provided information, medicines usage and safety, and Medication ADRs. Patients who bought medicines on prescriptions were more likely to have better knowledge. Patients having education were more likely to have better knowledge. Conclusion: Public awareness about medicine information, safety, and the information provided by manufacturers is crucial to ensuring that patients have access to accurate information about their medications and can make informed decisions about their health. Healthcare providers and regulatory bodies must work together to improve access to information and promote safe medication practices.

Exploring the Potent Combination of Quercetin-Boronic Acid, Epalrestat, and Urea Containing Nanoethosomal Keratolytic Gel for the Treatment of Diabetic Neuropathic Pain: In Vitro and In Vivo Studies.

Transdermal penetration of therapeutic moieties from topical dosage forms always remains a challenge due to the presence of permeation impeding keratin which should be addressed. The purpose of the study was to formulate quercetin and 4-formyl phenyl boronic acid (QB complex) used for the preparation of nanoethosomal keratolytic gel (EF3-G). The QB complex was confirmed by Fourier transform infrared spectroscopy while skin permeation, viscosity, and epalrestat entrapment efficiency were used for the optimization of nanoethosomal gel. The keratolytic effect of the proposed nanoethosomal gel with urea (QB + EPL + U) was calculated in rat and snake skin. The spherical shape of nanoethosomes was confirmed by scanning electron microscopy. According to the findings of stability studies, viscosity decreases as temperature increases, proving their thermal stability. The negative charge of optimized EF3 with 0.7 PDI proved narrow particle size distribution with homogeneity. Optimized EF3 showed two folds increase of epalrestat permeation in highly keratinized snake skin as compared to rats' skin after 24 h. Antioxidant behaviors of EF3 (QB) > QB complex > quercetin > ascorbic acid proved reduction of oxidative stress in DPPH reduction analysis. Interestingly, the hot plate and cold allodynia test in the diabetic neuropathic rat model reduced 3-fold pain as compared to the diabetic control group which was further confirmed by in vivo biochemical studies even after the eight week. Conclusively, ureal keratolysis, primary dermal irritation index reduction, and improved loading of epalrestat render the nanoethosomal gel (EF3-G) ideal for the treatment of diabetic neuropathic pain.

Formulation, optimization and in vitro evaluation of sustained release oral hydrogels of diacerein to treat arthritis.

The current study is aimed to formulate pH responsive polymeric hydrogels. Potassium per sulphate and Methylene bis acrylamide were employed as initiator and cross linker respectively. To determine the effect of substrate on degree of cross linking different ratios of the acrylic acid (AA), potassium per sulphate (KPS) and methylenebisacrylamide (MBA) were used. Swelling experiments were conducted in both basic and acidic media. Phosphate buffer of pH 7.4 and 0.1N HCl solution were used for swelling experiment of hydrogels. The hydrogels were more responsive towards basic medium as compared to acidic environment. Formulations were also evaluated for In vitro evaluation. Diacerein was selected model drug for hydrogel. Release pattern of the diacerein was studied both in acidic (0.1N HCl solution) and basic medium. Percentage drug release from M3 formulation showed as cross linker concentration increase (0.03%) drug release decrease Hydrogel samples were characterized by FTIR to confirm the functional groups of the hydrogels and their components and scanning electron spectroscopy (SEM) was performed to characterize the structure or morphology of the hydrogels. Finally, the dissolution studies were performed to evaluate the sustain release property of the hydrogel samples. Results show that all formulations of hydrogels are pH-sensitive and follow zero-order kinetics for drug release. Hence, optimized nexus (M3) serves as excellent carrier for target drug delivery.

Synthesis and characterization of self-assembling chitosan-based nanoparticles.

Chitosan (CHT) based biodegradable nanovectors were synthesized and modified with poly ethylene glycol 4000 (PEG-4000). CHT having medium molecular weight with 75% to 85% deacetylation was phthaloylated with phthalic anhydride, followed by PEGylation using PEG-4000. After confirmation of successful PEGylation by fourier transforminfra red spectroscopy (FTIR), the modified polymer was further processed to develop the nanocarrier using ionic gelation method by the addition of sodium tripolyphosphate (NaTPP). The prepared nanocarriers were subjected to physicochemical evaluation. The surface morphology of the particles was observed under scanning electron microscope (SEM), and particle size by dynamic light scattering (DLS) method, which was about 159-170nm in diameter. The zeta potential of the prepared nanovectors was +0.907mV which was due to cationic nature of nanovectors. The cell viability studies were also conducted to find the suitability of the carrier for in-vivo application, using liver cancerous cells (Hep G2). The findings have disclosed the concentration dependent activities of the particles, as viability of the cell was shown to be decreased with the increase in the concentration of the particles. Conclusively, the study was successful in determining the toxicity profile of these nanovectors as these were proved non-toxic at specific concentration.

GC-MS analysis, anticancer and anti-inflammatory activities of Saussurea hypoleuca spreng. Root.

Study has been premeditated to appraise the anticancer and anti-inflammatory activities of a native medicinal plant Saussurea hypoleuca Spreng root. Anticancer assays including MTT, Alamar Blue (AB), Neutral Red (NR) & LDH were employed on root methanolic extract (RME) and all fractions to calculate % age of cell viability and cell cytotoxicity. All fractions of plant root were tested for in vitro as well as in vivo anti-inflammatory assays by reported methods. GC-MS analysis of n-hexane: chloroform fractions in column chromatography has shown isopropyl myristate, hexadecanoic acid, 11-octadecenoic acid, Di-n-octyl phthalate, dioctyl ether, decanedioic acid, 1H-3a,7-Methanoazulene, 3,4-hexanedione and Tetracosapentaene. Percentage of cell viability in anticancer assays was significantly high in all fractions. However, whole results were momentous with ethyl acetate and aqueous fractions owning to excellent profile in evaluating cytotoxicity in each assay. COX-2 inhibition was calculated which was high in RME (68.69%), ethyl acetate (56.52%), aqueous (55.21%) and chloroform fraction (53.47%). Carrageenan and formalin models were developed on rats to investigate in vivo anti-inflammatory activity. RME (56.19%, 71.09%, 66.4%, 67.99%) and ethyl acetate (51.36%, 64.97%, 55.63% & 61.01%) produced significant % age inhibition in dose dependent manner at 200 and 400 mg/kg doses respectively. All above findings direct that plant root holds strong anticancer and anti-inflammatory activities.

Perceptions of and barriers to ethical promotion of pharmaceuticals in Pakistan: perspectives of medical representatives and doctors.

BACKGROUND: In Pakistan, drug promotion practices, ethical or unethical, have rarely been in the spotlight. We aimed to assess the perception and barriers of medical representatives (MRs) and doctors (MDs) regarding ethical promotion of pharmaceuticals in Pakistan. METHODS: A cross sectional survey was conducted in seven major cities of Pakistan for 6-months period. Self-administered questionnaire was used for data collection. Logistic regression and five-point Likert scale scoring was used to estimate the perceptions and barriers. RESULTS: Compared to national companies (NCs), the medical representatives (MRs) of multinational companies (MNCs) strongly believed that their companies follow World Health Organization (WHO) (OR; 5.31, p = 0.0005), International Federation of Pharmaceutical Manufacturers & Associations (IFPMA) (OR; 6.45, p = 0.0005) and national codes of ethics (OR; 5.84, p = 0.0005). MNCs trained their MRs (OR; 6.68, p = 0.0005), provide accurate and valid scientific data (OR; 4.01, p = 0.007) with adequate system of accountability and controls on product samples (OR; 1.96, p = 0.047), while, NCs sponsor social or entertainment activities, seminars and conferences, and all sort of facilitation in form of gifts of their choice and clinic renovation for medical doctors (MDs). MDs perceptions were similar to MRs mentioned above, yet strongly agreed that companies offer cash payments or equivalents to MDs. The MRs of NCs/MNCs and MDs agreed/strongly agreed that no external accountability, profiteering, pressure on sale targets, job insecurity, condoning unethical promotion by high-ups' and business promotion by junior MDs were the predominant barriers. CONCLUSION: In conclusion, MRs of MNCs and MDs believed that MNCs follow certain codes of ethics in the promotion of pharmaceuticals, while NCs tend to be more profit oriented and even condone unethical promotion. All stakeholders, MRs, MDs and companies, might pose certain barriers, intentionally or unintentionally, in ethical promotion.

Comparison of clinico-pathological characteristics and survival of recurrent ovarian cancer patients on seven different chemo-protocols.

Despite growing prevalence of ovarian cancer (OC) in Pakistan, no literature evidence exists regarding its clinic-pathological characteristics, survival and compliance of patients with recurrent ovarian cancer on various chemo-protocols. An observational study was conducted by enrolling 251 recurrent OC patients on 7 different chemo-protocols, from a specialized cancer care hospital, Lahore, Pakistan, using convenient judgmental sampling. The study was conducted for a period of 6 months. Most of the patients were between 18 and 70 years of age, with IIIC FIGO stage and papillary serous histological grade. As per RECIST, improved partial response (PR) (63.3 %) and complete response (CR) (52.1 %) was observed in the CP (carboplatin + paclitaxel) arm, substantiated by improved median progression free survival (PFS) and overall survival (OS) in CP and CD (carboplatin + docetaxel) arms, respectively, yet with no significant differences in survival curves, PFS (p = 0.12) and OS (p = 0.22). Interestingly, the highest and the lowest patient non-compliance were observed in CG (carboplatin + gemcitabine) (81.6 %) and paclitaxel (4.5 %) arms, resp. As per the hazard model for survival, topotecan showed significant association with the therapy related events/deaths compared to other protocols. These data suggest that CP regimen exhibited improved clinical efficacy and decreased toxicity related non-compliance in recurrent ovarian cancer patients of Lahore.

A randomized control trial of primary care-based management of type 2 diabetes by a pharmacist in Pakistan.

BACKGROUND: The role of a pharmacist in primary health care settings of Pakistan is still obscure. Thus, we aimed to demonstrate the pharmacist-led improvements in glycemic, blood pressure and lipid controls in type 2 diabetes mellitus (T2DM) patients of Lahore, Pakistan. METHODS: The first open label, randomized control trial conducted at a primary health care facility of Lahore, Pakistan by enrolling 244 uncontrolled type 2 diabetes (hemoglobin A1 c, (HbA1c); 10.85 ± 1.74) patients. The pharmacological intervention included identification of drug related problems, drug interactions, change in dose, frequency and therapy switches in collaboration with physician, while non-pharmacological intervention consisted of diet, lifestyle and behavior counseling. Outcome measures were glycemic (HbA1c), blood pressure and lipid controls. RESULTS: In intra-group comparison, compared to control arm (C, n = 52), subjects in the intervention arm (I, n = 83) demonstrated significant differences in process outcome measures; baseline vs final, such as HbA1c (C; 10.3 ± 1.3 vs 9.7 ± 1.3, p <  0.001, I; 10.9 ± 1.7 vs 7.7 ± 0.9, p <  0.0001), systolic blood pressure (SBP) (C; 129.9 ± 13.9 vs 136 ± 7.1, p = 0.0001, I; 145 ± 20.4 vs 123.9 ± 9.9 mmHg, p <  0.0001), diastolic blood pressure (DBP) (C; + 4, p = 0.03, I; - 7 mmHg, p <  0.0001), cholesterol (C; 235.8 ± 57.7 vs 220.9 ± 53.2, p = 0.15, I; 224 ± 55.2 vs 153 ± 25.9 mg/dL, p < 0.0001), triglycerides (C; 213.2 ± 86.6 vs 172.4 ± 48.7, p = 0.001, I; 273 ± 119.4 vs 143 ± 31.6 mg/dL, p < 0.0001) and estimated glomerular filtration rate (eGFR) (C; 77.5 ± 18.6 vs 76 ± 14.2, p = 0.5, I; 69.4 ± 21.3 vs 93.8 ± 15.2 ml/min/1.73m2, p < 0.0001). Likewise, inter-group improvements were more significant in the subjects of intervention group at final follow up in comparison to control for various process outcome measures; HbA1c (p < 0.001), SBP (p < 0.0001), DBP (p = 0.02), cholesterol (p < 0.0001), triglycerides (p < 0.0001), SCr (p < 0.001), eGFR (p < 0.001). Moreover, both male and female subjects exhibited similar responses towards intervention with similar improvements in outcome measures. CONCLUSION: These data suggested that pharmacist intervention in collaboration with physician in primary health care settings may result in significant improvements in glycemic, blood pressure and lipid controls in Pakistani population. TRIAL REGISTRATION: The trial was registered retrospectively with International Standard Registered Clinical/soCial sTudy Number (ISRCTN) registry on July 26, 2017 under nutritional, metabolic, endocrine category with assigned registration # ISRCTN22657497 and can be assessed at https://doi.org/10.1186/ISRCTN22657497.

Review: Nigella sativa (Prophetic Medicine): A Review.

The present report is a significant effort to explore detail description of N. Sativa, its pharmacognostic characteristics, morphological characteristics, and mechanism of actions, doses and medicinal uses. Nigella sativa (N. Sativa) is greatest form of healing medicine. It is also known as Prophetic Medicine as its use has been mentioned in Prophetic Hadit, as natural remedy for all the diseases except death. It is recommended on daily basis in Tibb-e-Nabwi (Prophetic Medicine). Hazrat Abu Hurairah States ''I have heard from Rasool Allah (PBUH) that there is cure for every disease in black seeds except death and black seeds are shooneeze''. Salim Bin Abdullah narrates with reference to his father Hazrat Abdullah Bin Omar that Rasool Allah (PBUH) said, 'Let all the black seed upon you, these contain cure of all diseases except death'. N. sativa claimed to have anti-inflammatory, analgesic, hepato-protective, neuro-protective, gastro-protective and other useful properties. Biological and pharmacological effects are attributed to its two important constituents Thymoquinone (TQ) and Nigella sativa oil (NSO). TQ has interaction with human serum albumin. Seeds containing volatile oils mainly Melanthin showed toxicity at larger doses. This report is a reference for all pharmaceutical researchers, physicians and biologists researching on N. sativa and will open a door towards novel agent.

Mesenchymal stem cells (MSCs) as skeletal therapeutics - an update.

Mesenchymal stem cells hold the promise to treat not only several congenital and acquired bone degenerative diseases but also to repair and regenerate morbid bone tissues. Utilizing MSCs, several lines of evidences advocate promising clinical outcomes in skeletal diseases and skeletal tissue repair/regeneration. In this context, both, autologous and allogeneic cell transfer options have been utilized. Studies suggest that MSCs are transplanted either alone by mixing with autogenous plasma/serum or by loading onto repair/induction supportive resorb-able scaffolds. Thus, this review is aimed at highlighting a wide range of pertinent clinical therapeutic options of MSCs in the treatment of skeletal diseases and skeletal tissue regeneration. Additionally, in skeletal disease and regenerative sections, only the early and more recent preclinical evidences are discussed followed by all the pertinent clinical studies. Moreover, germane post transplant therapeutic mechanisms afforded by MSCs have also been conversed. Nonetheless, assertive use of MSCs in the clinic for skeletal disorders and repair is far from a mature therapeutic option, therefore, posed challenges and future directions are also discussed. Importantly, for uniformity at all instances, term MSCs is used throughout the review.

PELLETS AND PELLETIZATION: EMERGING TRENDS IN THE PHARMA INDUSTRY.

The present time is considered as an era of advancements in drug delivery systems. Different novel approaches are under investigation that range from uniparticulate to multi particulate system, macro to micro and nano particulate systems. Pelletization is one of the novel drug delivery technique that provides an effective way to deliver the drug in modified pattern. It is advantageous in providing site specific delivery of the drug. Drugs with unpleasant taste, poor bioavailability and short biological half-life can be delivered efficiently through pellets. Their reduced size makes them more valuable as compared to the conventional drug deliv- ery system. Different techniques are used to fabricate the pellets such as extrusion and spheronization, hot melt extrusion, powder layering, suspension or solution layering, freeze pelletization and pelletization by direct compression method. Various natural polymers including xanthan gum, guar gum, tragacanth and gum acacia, semisynthetic polymers like cellulose derivatives, synthetic polymers like derivatives of acrylamides, can be used in pellets formulation. Information provided in this review is collected from various national and intemational research articles, review articles and literature available in the books. The purpose of the current review is to discuss pellets, their characterizations, different techniques of pelletization and the polymers with potential of being suitable for pellets formulation.

Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.

Phytochemical analysis, antioxidant and antibacterial effects of sea buckthorn berries.

Sea buckthorn berries are therapeutically used as folk medicine for a variety of diseases, however, the scientific evidence is hardly available to support their role. This study explored their chemical constituents and their role as antioxidant and antibacterial agents. Three common solvents such as petroleum ether (40° - 60°C), chloroform and methanol were successively used for the extraction of active principles from sea buckthorn berries. Five major fractions (F1-F5) were isolated from the active methanol extract by column and thin layer chromatography. An attempt was made to identify the chemical nature of pooled fractions by available spectral means. Antioxidant potential of methanol extract and its fractions was measured by DPPH, formation of phosphomolybdenum complex and TBA methods. The hole-plate diffussion method was used to find out the antibacterial activity. A very brief structure-activity relationship of the potent antioxidant and antimicrobial compounds is discussed. Methanolic extract and its fractions contain numerous phenolic compounds such as flavonoids, which may be responsible for antioxidant and antibacterial effects.