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What Happens After Biologics are Subcutaneously Administrated?

Let’s talk about the distribution of biologics. So after administration, proteins are transported to the blood circulation via the lymphatic tissues. Now, this is in contrast with small molecule. Small molecules enter the blood circulation through the capillary. So the higher the molecular weight, the less vascular absorption, the more lymphatic transport. A lymphatics transport rate is slower compared with the vascular transport. Here let’s look at it again. Small molecules is absorbed into the blood through the capillary, small capillaries. And the large molecules, the protein or the biological molecules are absorbed through the lymph. And then of course, eventually carried to the blood circulation, the molecular effect on lymphatic absorption.
Here we have the lymph recovery of the biologics, versus the molecular weight on the x axis. Let’s look at the floxuridine(FUdR), insulin, cytochrome and interferon. And as you can tell, the larger the molecular weight, the more lymphatic recovery of that particular protein. So the lymphatic absorption is predominant for proteins after the molecular weight exceeds 16000. The other way to improve bioavailability is to decrease elimination. Let’s look at the route, we can use IV infusion instead of IV injection. We can use SC instead of IM or IV route of biologics administration. Or we can work on the dosage form. We can use suspension for vaccines and protein products, or we can use implant for growth hormone.
We can also modify the molecular structure by chimerization that is humanization of the biologics. Pegylation. And glycosylation.

After SC administration, protein drugs can be transported to the systemic circulation directly via blood capillaries or indirectly via the lymphatics, both of which contribute to the absorption of protein drugs from the subcutaneous interstitial region. Small peptides and proteins (<16 kDa) primarily leave the subcutaneous site after injection by diffusion into blood capillaries. Transport of larger proteins from the subcutaneous site involves travel through the interstitium and into the lymphatic system. It has been demonstrated that lymphatic recovery after SC injection directly correlate with molecular mass.

Subsequent to the pervious video, suspension and implant are also presented as alternative dosage forms, exploiting their prolonged release property. In addition, structural modifications such as chimerization, glycosylation and pegylation are perceived from a dispositional point of view to decrease the rate of biologic elimination Most distinctively, biologics are distributed or transported via the lymphatic system, whereas the small molecule drugs are distributed through the capillaries

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Pharmacotherapy: Understanding Biotechnology Products

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