Biopharmaceutical Delivery Report PDF

Report on Delivery of Biopharmaceuticals Under Supervision of Pharmaceutical Department Prepared by Reham Saber Rogina Adel Hager Gaber Maha Essam Introduction Biopharmaceuticals have become a cornersto...

Report on Delivery of Biopharmaceuticals Under Supervision of Pharmaceutical Department Prepared by Reham Saber Rogina Adel Hager Gaber Maha Essam Introduction Biopharmaceuticals have become a cornerstone of the pharmaceutical industry, with rapid growth in product availability, and development pipelines. Their ability to target diverse diseases underscores their transformative potential. Examples include peptides, recombinant proteins, enzymes, and monoclonal antibodies. Advantages of biopharmaceutical drugs include high specificity and potency: their macromolecular nature allows for structural complexity, which ensures precise targeting of biological pathways compared to small molecules. Challenges in Formulation and Delivery Stability Issues:  Biopharmaceuticals are highly sensitive to environmental conditions (moisture, temperature), leading to loss of activity during storage or inside the body.  Example: Proteins may denature under suboptimal conditions. Delivery Barriers:  Low Permeability: Due to their high molecular mass, these drugs struggle to cross biological barriers such as skin, mucosal membranes, and cell membranes.  Limited Routes of Administration: Injection is often the primary method due to poor membrane permeation and low oral bioavailability.  Targeting Challenges: Delivering these drugs to specific intracellular sites is difficult, limiting their therapeutic effectiveness. Advances in Delivery and Formulation Parenteral Formulations:  Development of advanced injectable formulations (e.g., microspheres, hydrogels) has made biopharmaceutical delivery more efficient. Emerging Strategies:  Nanotechnology: Nanocarriers (e.g., liposomes, polymeric nanoparticles) improve targeting and stability.  Transdermal Systems: Emerging technologies aim to bypass traditional barriers (e.g., microneedles for direct skin delivery).  Controlled Release Systems: Prolong drug activity and reduce the frequency of dosing. Microspheres Microspheres are solid spherical particles (1-1000 nm in size), typically made of polymers (such as polystyrene, PLGA or silica. They have a solid core and are designed to encapsulate drugs within the matrix or on the surface. Advantages of Microspheres  Prolonged and Controlled Therapeutic Effect: Microspheres provide controlled and extended drug release.  Improved Patient Compliance: Microencapsulation minimizes gastrointestinal irritation, and reduced dosing frequency improves patient comfort.  Enhanced Bioavailability: Microspheres improve drug utilization, bioavailability, and reduce adverse effects. Limitations of Microspheres  Modified Release: The release rate may vary due to factors such as food intake and gastrointestinal transit time.  Potential Toxicity: High drug load in controlled release formulations means that any failure in the dosage form’s integrity could lead to toxicity.  Restrictions on Dosage Forms: These formulations should not be crushed or chewed as it may affect their release properties. Types of Microspheres 1. Bioadhesive Microspheres o Use water-soluble polymers for adhesion to mucosal membranes (buccal, ocular, rectal,..). o Improved therapeutic action due to better contact with the absorption site. 2. Magnetic Microspheres o Respond to a magnetic field due to incorporated materials like chitosan or dextran. o Deliver chemotherapeutic agents (proteins, peptides) to targeted sites like liver tumors. 3. Floating Microspheres o Bulk density is lower than gastric fluid, allowing buoyancy in the stomach. o Slows drug release, prolongs gastric residence time, and reduces plasma concentration fluctuations. 4. Radioactive Microspheres o Sized 10-30 nm, injected into arteries leading to tumors. o Trapped in capillary beds, delivering high radiation doses directly to the tumor  Nanotechnology  Nanoparticles are solid colloidal particles ranging from 1 to 100 nm in size.  Nanoparticles can be prepared using a wide range of materials, including polymers, lipids, proteins, metals, and minerals.  They are composed of macromolecular materials and can incorporate active agents through dissolution, entrapment, encapsulation, adsorption, or attachment. Advantages:  Biocompatibility and Biodegradability: Essential for safe and effective drug delivery.  Protection of Drugs: Encapsulation shields drugs like proteins from degradation.  Sustained Release: Prolonged drug delivery enhances therapeutic efficacy.  Site-Targeted Delivery: minimizes systemic side effects and maximizes therapeutic efficacy. Liposomes Liposomes are vesicles fluid-like structures with an internal aqueous core and an external lipid bilayer, which allows for the encapsulation of both hydrophilic and lipophilic drugs. Classification of Liposomes  Conventional Liposomes: Basic liposomes without surface modifications.  pH-Sensitive Liposomes: Designed to release their contents in acidic environments, such as tumor sites.  Cationic Liposomes: Positively charged liposomes used primarily for gene delivery.  Immunoliposomes: Liposomes with antibodies or ligands attached for targeted drug delivery. Factors Affecting Liposome Performance 1. Permeability and Penetration Capacity: Liposomes, due to their structural similarity to cell membranes, can merge with cellular bilayers, enhancing drug delivery across biological barriers. 2. Drug Loading Capacity: A balanced drug-to-lipid mole ratio is critical. Excessive drug loading disrupts the lipid bilayer, reducing stability and therapeutic effectiveness. 3. Surface Modification: Modifications, such as PEGylation, prevent rapid clearance by the immune system, extending circulation time.  Microneedle Technology  The microneedle system consists of tiny, submillimetre-sized needles (up to 1500 μm) attached to a base support.  These needles penetrate the outermost skin layer (stratum corneum) and deliver drugs to the viable epidermis, bypassing pain-sensitive dermal layers that contain nerve fibers and blood vessels.  (MNs) offer a wide range of drug delivery approaches, which are non-invasive, pain-free, and self-administered, making them a compelling alternative to traditional hypodermic needles. Microneedle-Based Delivery Approaches 1. Solid Microneedles ("Poke and Patch"): It is applied to create small holes in the skin, followed by the topical application of the drug. 2. Coated Microneedles ("Poke and Coat") :Therapeutic agents are coated on the surface of solid microneedles. 3. Hollow Microneedles ("Poke and Flow") : allow the controlled flow of therapeutic agents into the skin, potentially using diffusion or pressure. 4. Dissolving Microneedles ("Poke and Dissolve") : Water-soluble therapeutic agents are carried into the skin by dissolving microneedles made of biodegradable polymers. Conclusion  Biopharmaceuticals offer targeted, potent treatments but face challenges in stability, permeability, and limited administration routes.  Microspheres enable controlled drug release and improved bioavailability but may have toxicity risks and inconsistent release rates.  Nanotechnology (liposomes, nanoparticles) improves drug protection, sustained release, and targeted delivery, with strong potential for protein and peptide drugs.  Microneedles provide a non-invasive, pain-free delivery system, overcoming skin barriers for efficient drug administration.  These delivery innovations enhance therapeutic outcomes and patient adherence, with ongoing advancements expected to broaden their applications and overcome current limitations. References 1. Mitragotri, S."Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies" Nature Reviews Drug Discovery (2014). https://doi.org/10.1038/nrd4363 2. Kumar N. Verma "Recent Advances in Microspheres Technology for Drug Delivery". International Journal of Pharmaceutical Sciences and Nanotechnology (2015) 10.37285/ijpsn.2015.8.2.2 3. Ana C. Silva "Delivery Systems for Biopharmaceuticals. Part I: Nanoparticles and Microparticles" Current Pharmaceutical Biotechnology (2015) 10.2174/1389201016666150731112532 4. Khafoor A. Ali "Recent progress in synthesis of nano based liposomal drug delivery systems: A glance to their medicinal applications" Results in Surfaces and Interfaces (2023) https://doi.org/10.1016/j.rsurfi.2023.100124 5. Muhammet Avcil , Ayhan Çelik "Microneedles in Drug Delivery: Progress and Challenges" Micromachines (2021) 10.3390/mi12111321 Questions 1. What is a common method of administering biopharmaceutical drugs due to low permeability across biological barriers? A)Oral tablets B) Injection C) Topical application D) Inhalation Answer: B) Injection 2. Which type of microneedle involves the controlled flow of therapeutic agents into the skin? A)Solid microneedles B) Coated microneedles C) Hollow microneedles D) Dissolving microneedles Answer: C) Hollow microneedles 3. Which type of liposome is designed to release its contents in acidic environments such as tumor sites? A)Conventional liposomes B) pH-sensitive liposomes C) Cationic liposomes D) Immunoliposomes Answer: B) pH-sensitive liposomes 4. Which of the following is the main concern regarding the release rate of microspheres in drug delivery? A)Release is always consistent regardless of conditions B) The release rate is highly affected by external factors like food intake and gastrointestinal transit time C) Microspheres increase the release rate significantly compared to oral formulations D) The drug release rate does not vary and remains predictable Answer: B) The release rate is highly affected by external factors like food intake and gastrointestinal transit time 5. Which of the following is true about the drug loading capacity of liposomes? A)Excessive drug loading can enhance the stability and performance of liposomes B) The drug-to-lipid mole ratio must be balanced to maintain liposome stability and  effectiveness C) Liposomes are best used for non-polar drugs that do not dissolve in water D) Liposomes function best without any surface modifications Answer: B) The drug-to-lipid mole ratio must be balanced to maintain liposome stability and effectiveness 6. What is the main advantage of using dissolving microneedles over other types of microneedles? A) They allow for faster drug release B) They provide a non-invasive drug delivery without the need for a patch C) They use biodegradable polymers that dissolve to release the drug directly into the skin D) They provide a permanent solution for drug delivery Answer: C) They use biodegradable polymers that dissolve to release the drug directly into the skin 7. What is the purpose of PEGylation in liposomes? A) To increase the liposome's solubility in aqueous solutions B) To allow the liposome to deliver multiple drugs simultaneously C) To prevent rapid clearance by the immune system, thereby extending the circulation time D) To enhance liposome stability by increasing drug encapsulation capacity Answer: C) To prevent rapid clearance by the immune system, thereby extending the circulation time 8. How do floating microspheres enhance the pharmacokinetics of the drug they deliver? A) By speeding up the release of the drug for immediate effect B) By improving drug solubility in the bloodstream C) By increasing gastric residence time and reducing plasma concentration fluctuations D) By decreasing the absorption rate of the drug in the stomach Answer: C) By increasing gastric residence time and reducing plasma concentration fluctuations 9. Which of the following best describes the function of immunoliposomes in drug delivery? A) They release the drug in response to external magnetic fields B) They encapsulate hydrophobic drugs for enhanced stability C) They are designed to target specific cells or tissues by attaching antibodies or ligands to their surface D) They are used to bypass the gastrointestinal tract and deliver drugs directly to the bloodstream Answer: C) They are designed to target specific cells or tissues by attaching antibodies or ligands to their surface.