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Syed Khurram Azmat,1 Waqas Hameed,1 Anja Lendvay,2 Babar Tasneem Shaikh,3 Ghulam Mustafa,1 Muhammad Ahmed Siddiqui,1 Sajid Brohi,1 Asif Karim,1 Muhammad Ishaque,1 Wajahat Hussain,1 Mohsina Bilgrami,1 Paul J Feldblum2 1Research, Monitoring and Evaluation Department, Marie Stopes Society, Karachi, Pakistan; 2FHI 360, Durham, NC, USA; 3Health Services Academy, Islamabad, Pakistan Introduction: The use of hormonal implants has gained positive traction in family planning programs in recent times. Compared to other popular methods, such as long-term reversible intrauterine devices, the use of hormonal implants as a family planning method has distinct advantages in terms of long-term efficiency and better user compliance and availability. This paper presents a study protocol to document and evaluate the efficacy, safety, and acceptability of Femplant (contraceptive implant) in Pakistan during the first year of its use among married women of reproductive age (18–44 years) at clinics in two provinces of Pakistan (Sindh and Punjab). Materials and methods: A total of 724 married women were enrolled in a noncomparative prospective observational study. The study involved six government clinics from the Population Welfare Department in Sindh Province and 13 clinics run by the Marie Stopes Society (a local nongovernmental organization) in both provinces. The participation of women was subject to voluntary acceptance and medical eligibility. All respondents were interviewed at baseline and subsequently at each scheduled visit during the study period. Side effects, complications and adverse events, if any, were recorded for every participant at each visit to the facility. Discussion: Over the next 5-year period (2013–2018), 27 million hormonal implants will be made available in lower- to middle-income countries by international donors and agencies. The evidence generated from this study will identify factors affecting the acceptability and satisfaction of end users with Femplant (Sino-implant II). This will help to guide policies to enhance access to and the use of long-acting contraceptive implants in Pakistan and similar developing countries. Keywords: safety, efficacy, acceptability, implant, Femplant, contraception, family planning, Pakistan

Liposome co-encapsulation of synergistic anti-cancer drug combination is an emerging area that has demonstrated therapeutic benefit in clinical trials. Remote loading of two or more drugs into a single liposome constitutes a new challenge that calls for a re-examination of drug loading strategies to allow the loading of the drug combination efficiently and with high drug content. In this study, the Mn 2 + gradient coupled with A23187 ionophore was applied in the sequential co-encapsulation of doxorubicin and irinotecan, as this drug loading method is capable of remotely loading drugs by apparently two different mechanisms, namely, coordination complexation and pH gradient. Doxorubicin and irinotecan could be co-encapsulated into liposomes in a wide range of drug-to-drug ratios, with encapsulation efficiencies of > 80%. The total encapsulated drug content was non-linearly correlated with increases in the intraliposomal Mn 2 + concentration, with a maximum total drug-to-lipid molar ratio of 0.8:1 achieved with 600 mM Mn 2 + . This high encapsulated drug content did not affect the stability of the co-encapsulated liposomes upon storage for six months. Regardless of the encapsulated drug amount, the liposomes did not exhibit the fiber bundle precipitate morphology but rather an undefined structural organization in the aqueous core. The co-encapsulated liposome formulation was further tested in an intraperitoneally grown, human ovarian tumor xenograft model, and was shown to significantly improve the survival of the tumor-bearing animals. The improvement in therapeutic efficacy was possibly due to the increase in systemic drug exposure, with the maintenance of the synergistic molar drug ratio of 1:1 in circulation.

Contains fulltext : 118573.pdf (Publisher’s version ) (Open Access) Background and Objective: Interleukin (IL) 4 is a cytokine that mediates allergic responses. Different single nucleotide polymorphisms (SNPs) can influence the immune response mediated by cytokines. The aim of the present study was to investigate the possible association between IL-4 polymorphisms and allergic rhinitis and atopic asthma. Methods: A total of 214 atopic patients (108 with asthma and 106 with allergic rhinitis) and 120 healthy controls from Pakistan were genotyped for IL-4 SNPs C-589T (rs2243250), T+2979G (rs2227284), and C-33T (rs2070874) using restriction fragment length polymorphism-polymerase chain reaction. Statistical analysis was performed using the statistical software package StatCalc, EpiInfo v.6. Results: The SNP rs2243250 was significantly associated with both asthma (P=.004, ?2=11.0) and allergic rhinitis (P

The nasal route is a potential alternative route for systemic availability of drugs restricted to intravenous ad-ministration, such as peptide and protein drugs and vaccines. This route is also advisable for drugs undergoing extensive first pass effect .Besides this, intranasal route has also been successfully exploited for bypassing the blood brain barrier [BBB] and subsequently delivering drug molecules to central nervous system [CNS]. The present article highlights the advantages, barriers, physicochemical factors and formulation related parameters affecting the nasal drug delivery. It also includes a note on nasal absorption enhancers. Also, the applications of nasal route for delivery of peptides and proteins, non-peptide drugs, vaccines and drug molecules to CNS have been summarized in depth. Key Words : Nasal route, nasal absorption enhancers, peptide, protein drugs, vaccines, central nervous system. INTRODUCTION The nasal mucosa has been considered as a potential ad-ministration route to achieve faster and higher level of drug absorption. This is due to the large surface area, porous en-dothelial membrane, high total blood flow, the avoidance of first-pass metabolism, and ready accessibility. The nasal administration of drugs, including numerous compounds, peptide and protein drugs, for systemic medication has been widely investigated in recent years. In the recent past many researchers have also attempted delivery of drugs to the CNS through the nose. However, the major limitation with nasal route administration is the poor contact of the formulations with the nasal mucosa. Many attempts have been made in the recent past to increase the residence time of drug formula-tions in the nasal cavity, resulting in improved nasal drug absorption. Researchers became interested in the nasal route for the systemic delivery of medication due to high degree of vascularization and permeability of the nasal mucosa. Several researchers have studied the anatomical and physiological aspects of the nasal membrane, including its vascular nature, as they relate to drug delivery[1-8]. The nose is divided into two nasal cavities

Liposome co-encapsulation of synergistic anti-cancer drug combination is an emerging area that has demonstrated therapeutic benefit in clinical trials. Remote loading of two or more drugs into a single liposome constitutes a new challenge that calls for a re-examination of drug loading strategies to allow the loading of the drug combination efficiently and with high drug content. In this study, the Mn(2+) gradient coupled with A23187 ionophore was applied in the sequential co-encapsulation of doxorubicin and irinotecan, as this drug loading method is capable of remotely loading drugs by apparently two different mechanisms, namely, coordination complexation and pH gradient. Doxorubicin and irinotecan could be co-encapsulated into liposomes in a wide range of drug-to-drug ratios, with encapsulation efficiencies of80%. The total encapsulated drug content was non-linearly correlated with increases in the intraliposomal Mn(2+) concentration, with a maximum total drug-to-lipid molar ratio of 0.8:1 achieved with 600 mM Mn(2+). This high encapsulated drug content did not affect the stability of the co-encapsulated liposomes upon storage for six months. Regardless of the encapsulated drug amount, the liposomes did not exhibit the fiber bundle precipitate morphology but rather an undefined structural organization in the aqueous core. The co-encapsulated liposome formulation was further tested in an intraperitoneally grown, human ovarian tumor xenograft model, and was shown to significantly improve the survival of the tumor-bearing animals. The improvement in therapeutic efficacy was possibly due to the increase in systemic drug exposure, with the maintenance of the synergistic molar drug ratio of 1:1 in circulation.