A Systematic Review based on the Use of Au- and Pt-based Nanoparticles along with H₂ Blocker Medicines

INTRODUCTION

H₂ blockers or antagonists are histamine blockers that are included in the class of agents specific for suppressing gastric acid in different gastric conditions. These drugs are approved by Food and Drug Administration (FDA) to be used for a short duration to treat gastroesophageal reflux diseases, ulcers of the duodenum, hypersecretion of gastric juice, indigestion, and infrequent heartburn. RA is also used to treat esophagitis, prophylaxis, urticaria, and gastrointestinal hemorrhage. H₂ blockers are included in multidrug establishment for the eradication of Helicobacter pylori.^[1] H₂ blocker drugs can be also used during pregnancy as secondary medicine, although for heartburn during pregnancy antacids are preferred.^[2] H₂ Receptor Antagonist (H₂RA) is also considered safe for adolescent children with mild heartburn issues.^[3] The overall use of H₂ blockers depends on the rigorousness of gastric illness therapy duration and dosage regimen. H₂ blockers such as nizatidine, cimetidine, and famotidine are used more frequently. The mechanism of the action of H₂ blockers depends on the reverse binding of the histamine in the parietal cells of the digestive system as they limit endogenous ligands and also inhibit their binding mechanism. Hence, an H₂ blocker works as a good antagonist. Usually, gastric acid is released in the stomach after the meal when the histamine gets stimulated and releases the enterochromaffin cells which bind with H₂ receptors.^[4] When the intracellular cyclic Adenosine Monophosphate (cAMP) level is increased in the gastric cells by adenylate cyclase activation, more gastric acid is released. This cAMP activates protein kinase A which is involved in the movement of K⁺/H⁺ ATPase transporter through the plasma membrane, increased K⁺/H⁺ Adenosine Tri Phosphatase (ATPase) transport secretes more gastric acid in the parietal cells.^[5] Acid secretion of the parietal cells is stimulated when the histamine receptors are blocked.^[5] H₂ blockers have the capacity of gastric relief from 1 h to 5 h by decreasing the secretion of gastric juices, it is similar to the onset of gastric stroke.^[6]

Due to the wide therapeutic index of H₂ blocker, toxicity is quite rare. It can have associated with the blocking of H₂ receptors in case of myocardium issues and Central Nervous System (CNS) diseases such as depression, bradycardia, and hypotensive. These receptors are involved in rapid fusion veins of H₂ RA. The treatment related to H₂ RA toxicity requires decontamination of the gastric lavage or the use of activated charcoal with supportive care and discontinuation of the drugs.

TYPES OF H₂ BLOCKER DRUGS STUDIED

H₂ blockers are categorized basically into four types; ranitidine, nizatidine, famotidine, and cimetidine [Table 1]. These H₂ blockers are divided based on their ring structure [Table 2]. Two types of rings are seen, namely, the five-membered ring and the six-membered ring. In the present study, we emphasize two often used H₂ blocker drugs famotidine and nizatidine.

ROLE OF H₂ BLOCKER PUMP IN COVID-19

Histamines are released from mast cells which further stimulate the H₂ receptors for lung infection in the case of COVID-19 patients.^[12] In COVID-19-infected cells, expression of the toll-like receptor is increased by the histamine, secreted from the mast cells, and Toll Like Receptor 3 (TLR₃)-dependent signaling is reduced.^[13] The bactericidal action is also increased, which further increases phagocytosis and suppresses the production of peroxide. Natural Killer (NK) cell count and cytotoxicity are increased by the production of peroxide ions, which results in enhanced Cluster of Differentiation 40 (CD40), Major Histocompatibility Complex 1 (MHC 1), Interleukin 2 (IL 2), and function of dendritic cells.^[14] It has been reported that the use of famotidine an H₂ blocker is found effective in the treatment of patients suffering from COVID-19. Mather et al., 2020, reported a study where a total of 878 patients received famotidine in COVID-19 infection and were cured successively.^[15] They also reported low serum markers and the use of Cardio Pulmonary Resuscitation (CPR) in patients who received famotidine. A study published by Sun et al., 2021, also reported a better cure for COVID-19 in 36,635 patients receiving famotidine.^[16]

NANOPARTICLES

The birth of nanotechnology has been considered in existence after the famous lecture of Richard Feynman an American physicist in 1959. Nanotechnology has emerged its arms in almost every field either medicine, science, agriculture, or engineering. Inorganic and organic hybrid materials are utilized in the field of nanotechnology. Metals such as silver and copper are used by humankind due to their antimicrobial properties. Resonance properties of the plasmon such as Ag NPs are found in calorimetric sensors such as fluorescence sensors, chemiluminescence sensors, and Raman spectrometry.^[17] Nanotechnology develops at different levels such as devices, materials, and systems. In the present era, the most innovative study material is nanoparticles. These nanoparticles are microparticles or minor objects which are the complete unit and transport material. Nanoparticles are characterized based on their sizes such as diameter. The diameter of these particles ranges between 100 and 2500 nanometers, whereas the ultrafine particles range between 1 and 100 nanometers, this size is similar to ultrafine particles. The size-associated properties can or cannot be revealed by the nanoparticles, because properties in their nano form may vary from that in their bulk form.^[18] Thus, reduction in the size of the particles from bulk to nano makes a substantial difference in their properties. The nanoparticles can be polymer-based, metallic, or mineral or they can be a combination of different materials. All these types of nanoparticles are highly recommended for the generation of the drug in different fields of medicine and science. Selecting nanoparticles as important and unique drug material is because of a few properties such as a much larger surface mass ratio, capability to carry and adsorb drugs, proteinase, and probes, and promotion of the reaction catalytically.^[19]

ADVANTAGES OF USING NANOPARTICLES AS DRUG MATERIAL

Surface characteristics and particle size targeting the active and passive drug on parental administration are easy to manipulate. The nanoparticles provide easy higher therapeutic efficacy with fewer adverse effects, while transportation, they sustain and release the drugs at the target site, with altered drug distribution and clearance. Nanoparticles achieve the site-specific target by attracting the ligands on their surface. These particles can be administered by different routes such as intraocular, oral, nasal, and parenteral. Nanoparticles can achieve tiny sites easily because of their specific size. On the recommendation of the engineers, the researchers use these scales precisely and use these polymers based on their physical features and previously controlled biomaterials. Because of the tiny particle size, the nanoparticles easily deliver the drugs beyond the physiological barriers. Efficient delivery of the drugs is done by the nanoparticles because they are soluble in water and are capable to enhance the bioavailability of the drugs and can target the drug accurately. Nanoparticles can provide highly efficient and reduced drug toxicity. Nanoparticles can even be very helpful for the successful delivery of different biotechnological drugs to the anatomical extremities in the body such as BBB or the blood–brain barrier.

TYPES OF NANOPARTICLES

Nanoparticles are classified based on their morphology, size, chemical, and physical properties. Nanoparticles are enlisted in Table 2 based on their types.

CONCLUSION

At the time of prescription, the clinicians and pharmacist should have complete details of newly discovered medicine as H₂ blocker drugs and different nanoparticles. Interaction of different drugs, their availability, structures, and mode of interaction must be restudied thoroughly before initiating the treatment. This review provides complete information, about the generic names, scoring on the scale, and recommended doses of different H₂ blockers. It also provides detailed information on the different types of available nanoparticle-based drugs. The clinicians and pharmacists must inform the patients about the toxic effects of drugs before providing them. Educational materials should be provided to the patients so that they can recognize the generic medicines. This review is an endeavor to decrease the information gap and avoid the non-prescribed distribution of such drugs or self-medication. Unaware dangerous interaction of drugs due to self-medication results in an avoidable medical emergency, which should be strictly restricted.