Philomena Entsie

The neuropeptides vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) have emerged as potent modulators of immune responses during sepsis, yet their roles remain complex, alternating between protective and permissive depending on timing, tissue compartment, and inflammatory context. This review presents a historical assessment of VIP and PACAP in sepsis research, highlighting the evolution of conceptual advances across five decades. Starting in the 1980s, early studies revealed that VIP levels rise during endotoxemia and correlated with hypotension and mortality, suggesting a deleterious role. By the 1990s, research pivoted toward understanding gut-derived VIP and its interaction with nitric oxide, culminating in the classification of VIP and PACAP as “macrophage deactivating factors” that downregulate TNFα and IL-6. The 2000s further clarified their cell-specific actions through VPAC1/2 and PAC1 receptors, showing anti-inflammatory effects on both innate and adaptive immune cells, while illuminating delivery challenges overcome by liposomal encapsulation. The 2010s expanded this narrative by dissecting receptor dynamics, gut barrier regulation, and VIP’s role in neuroimmune crosstalk and thrombo-inflammation. Most recently, studies in the 2020s provide a nuanced view of how VIP suppresses inflammatory damage but also enables pathogen persistence during live bacterial infection, implicating VIP signaling in trade-offs between tolerance and clearance. Across this chronological framework, VIP and PACAP have oscillated between friend, foe, and frenemy, underscoring the importance of context in leveraging their therapeutic potential in sepsis.

Intra-abdominal sepsis is a challenging complication postabdominal surgery caused by perforations of the gastrointestinal tract where microbes invade the peritoneal cavity. This leads to local cytokine release and immune cell dysfunction. Our data identify platelets as key players in mediating inflammation in intra-abdominal sepsis. We have shown that blocking purinergic signaling in the peritoneal cavity reduced cytokine release and cell-cell interactions differently in males and females, hence a sex-specific strategy to improve intra-abdominal sepsis.

P2Y₁₂ is a G-protein-coupled receptor that is activated upon ADP binding. Considering its well-established role in platelet activation, blocking P2Y₁₂ has been used as a therapeutic strategy for antiplatelet aggregation in cardiovascular disease patients. However, receptor studies have shown that P2Y₁₂ is functionally expressed not only in platelets and the microglia but also in other cells of the immune system, such as in monocytes, dendritic cells, and T lymphocytes. As a result, studies were carried out investigating whether therapies targeting P2Y₁₂ could also ameliorate inflammatory conditions, such as sepsis, rheumatoid arthritis, neuroinflammation, cancer, COVID-19, atherosclerosis, and diabetes-associated inflammation in animal models and human subjects. This review reports what is known about the expression of P2Y₁₂ in the cells of the immune system and the effect of P2Y₁₂ activation and/or inhibition in inflammatory conditions. Lastly, we will discuss the major problems and challenges in studying this receptor and provide insights on how they can be overcome.

Pharmaceutical oral solutions are preparations in which the active ingredients are dissolved in suitable liquid vehicles such as syrups. This study sought to determine the potential of glucose syrup produced from high quality cassava flour (HQCF) as a vehicle or sweetener in the preparation of paracetamol syrup and simple linctus. Four formulations (two paracetamol syrups (B1 and B2) and two simple linctus formulations (A1 and A2)) were prepared using glucose syrup from HQCF as vehicle or sweetener while two controls (B3 and A3) were prepared for each group using sucrose syrup as vehicle or sweetener. Two brands of paracetamol syrup and simple linctus were purchased from retail pharmacies to serve as standards. Physical and organoleptic parameters such as pH, taste and color, microbial load, and drug content of all formulations were determined. All formulations passed the microbial load and drug content tests as specified by the British Pharmacopoeia. The paracetamol syrups were all sweet with characteristic bitter aftertastes except formulation B2 which was sweetened with sucralose. All the simple linctus formulations were sweet except A2 (sweetened with sucralose) which was very sweet. The taste masking capacity of the glucose syrup produced from HQCF matched that of the sucrose syrup in the products formulated. Therefore, glucose syrup from HQCF could be a suitable alternative to sucrose syrup as a vehicle or sweetener in oral liquid formulations and can ultimately reduce the cost of these oral liquid formulations.

Annona muricata (Annonaceae) is a tropical plant widely known for its edible fruits. Recent scientific studies have confirmed the folkloric use of its seeds as an antidiarrheal agent. This study sought to formulate capsules and suspensions using the ethanolic extract from Annona muricata seeds. The dried ethanolic extract was formulated into granules and subsequently encapsulated. The suspension formulated was assessed for sedimentation rate, sedimentation volume, viscosity, dissolution, drug content, and flow rate, while pharmacopeia tests such as disintegration, dissolution, uniformity of weight, and drug content were carried out on the formulated capsules. The formulated suspension passed the drug content and in vitro release studies. Annona muricata suspension exhibited pseudoplastic flow with good sedimentation rate and sedimentation volume. The formulated capsules passed the in vitro dissolution studies, weight uniformity, disintegration, and drug content tests. The ethanolic extract of Annona muricata seeds was appropriately formulated into standardized solid and liquid oral dosage forms.

Excipients are the various ingredients, apart from the active pharmaceutical ingredients, which are added to pharmaceutical formulations. Excipients obtained from natural sources are preferred over those from synthetic sources because they are cheap, biocompatible and readily available. Gums are made up of carbohydrate units which are linked by glycosidic bonds. This study was aimed at evaluating the potential binding and disintegrating properties of gum obtained from the bark of Cinnamomum zeylanicum, which was obtained from Effiduase in the Ashanti region of Ghana. The gum was extracted using 96% ethanol and the moisture content, Fourier transform infrared spectroscopy spectra, water holding capacity, swelling index and flow properties of the gum were determined. The gum was used to formulate tablets at different concentrations (10% w/v, 15% w/v and 20% w/v) as binder with acacia as the standard. The gum was also used to formulate tablets at different concentrations (5% w/v, 7.5% w/v and 10% w/v) as disintegrant with starch as the standard. Quality control tests were then conducted on all formulated tablets. The gum exhibited good flow and physicochemical properties. All formulated tablets passed the uniformity of weight test, friability test, disintegration test, hardness test, uniformity of dimensions test and drug content. All batches of tablets, except Batch 7, passed the dissolution test. Based on the study carried out, C. zeylanicum gum can be used as an alternative excipient to acacia and starch as a binder and a disintegrant, respectively. Significance: A natural polysaccharide (gum) from the bark of Cinnamomum zeylanicum tree can be harnessed and commodified as a pharmaceutical excipient (binder and disintegrant) in the production of immediate release tablets.

Malaria ranks amongst the major health challenges faced by many developing countries. In Sub-Saharan and tropical regions of Africa, malaria continues to claim the life of one out of every twenty children below the age of five years. In adults, mortality rates are lower, but frequent debilitating attacks reduce the quality of life for chronic sufferers. The patronage and usage of liquid herbal antimalarials in the management and treatment of malaria in Ghana have been on the ascendency over the past decade. This project seeks to transform five liquid herbal antimalarial preparations (Agbeve pevah, Time mixture, Givers mixture, Masada mixture, and Rooter mixture) produced locally and commonly used for the treatment of malaria fever into capsules. This will help eliminate the current limitations, such as lack of patient compliance due to the bitterness and bulky nature of packaged preparation. The amount of dry extract per dose of each herbal antimalarial preparation and the wavelength of maximum absorption (λ_max) of aqueous solutions of Agbeve, Time, Givers, Masada, and Rooter extract were determined. The flow properties of formulated granules were determined and subsequently encapsulated. The formulated capsules were evaluated using basic pharmacopeial tests, such as uniformity of weight, disintegration, drug content, and dissolution. Difference, f1, and similarity, f2, factors were employed in analyzing the dissolution profiles of the formulated capsules. The formulated granules exhibited good flow properties and passed the weight uniformity, disintegration, and drug content tests. The capsules exhibited optimal release of extract at the 45th minute in 0.1 M HCL. All formulated capsules had ƒ2 values >50 and ƒ1 values <15, indicating the similarity of their drug release profiles with their respective liquid herbal antimalarials. Oral capsules of Agbeve, Time, Givers, Masada, and Rooter have been successfully formulated and can be used as a substitute for Agbeve pevah, Time mixture, Givers mixture, Masada mixture, and Rooter mixture, respectively, in the treatment of malaria.

Natural polymers have become attractive to pharmaceutical researchers and manufacturers as excipients because of the advantages they possess relative to their semisynthetic and synthetic counterparts. Although pectin from some natural sources has been investigated for use in the pharmaceutical industry as excipients, pectin from okra, which is readily available and used as food in many parts of the world, has not been extensively investigated as a potential control-releasing agent in tablets. This study thus seeks to determine the drug release modifying properties of okra pectin from 6 different genotypes of okra cultivated and available in Ghana. Pectin was extracted from different genotypes of okra, physicochemical properties were characterized, and control release matrix tablets of metformin (F1F6) were formulated using the wet granulation method with the okra pectin as the drug release modifier, respectively. The drug content, in vitro drug release, and mathematical kinetic modeling of drug release from the matrix tablets were studied. Drug release profiles of formulated matrix tablets were compared to an existing (innovator) brand of metformin sustained-release tablet on the market using the similarity and difference factors, respectively. The extracted pectin had percentage yields ranging from 6 to 20 w/w with swelling indexes and water-holding capacities between 300500 and 9-10mL/g, respectively, and pH within 6.206.90. All the formulated batches passed the drug content test (90105) and produced the optimal release of metformin (80) after 24 hours. Different batches of formulated tablets exhibited different mechanisms of drug release with batches F1, F2, F5, and F6 being similar (ƒ₂ values being >50 and ƒ₁ values <15) to the innovator brand. Pectin from the 6 different genotypes of okra studied has the potential for use as drug release modifiers in pharmaceutical manufacturing of control release matrix tablets and production of more affordable medicines.